BackgroundGood syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging from various infections to autoimmunity.ObjectiveThis study was to summarize patient characteristics, identify prognostic factors and define clinical subgroups of Good syndrome.MethodsA systematic literature review was conducted to include patients with Good syndrome identified in PubMed, Embase and Cochrane databases between January 2010 and November 2020. Logistic and Cox regressions were used to identify prognostic factors impacting outcomes. Clinical subgroups were defined by multiple correspondence analysis and unsupervised hierarchical clustering. A decision tree was constructed to characterize the subgroup placement of cases.ResultsOf 162 patients included in the current study, the median age at diagnosis was 58 years and 51% were male. Type AB was the most common histological subtype of thymoma, and infections as well as concurrent autoimmune disorders were identified in 92.6% and 51.2% patients, respectively. Laboratory workup showed typical findings of combined immunodeficiency. Thymoma status (odds ratio [OR] 4.157, confidence interval [CI] 1.219-14.177, p = 0.023), infections related to cellular immunity defects (OR 3.324, 95% CI 1.100-10.046, p = 0.033), infections of sinopulmonary tract (OR 14.351, 95% CI 2.525-81.576, p = 0.003), central nerve system (OR 6.403, 95% CI 1.205-34.027, p = 0.029) as well as bloodstream (OR 6.917, 95% CI 1.519-31.505, p = 0.012) were independent prognostic factors. The 10-year overall survival was 53.7%. Cluster analysis revealed three clinical subgroups with distinct characteristics and prognosis (cluster 1, infections related to cellular immunity defects; cluster 2, infections related to other immunity defects; cluster 3, infections related to humoral and phagocytic immunity defects). A decision tree using infection types (related to humoral and cellular immunity defects) could place patients into corresponding clusters with an overall correct prediction of 72.2%.ConclusionsInfection type and site were the main prognostic factors impacting survival of patients with Good syndrome. We identified three subgroups within Good syndrome associated with distinct clinical features, which may facilitate the study of underlying pathogenesis as well as development of targeted therapy.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is a multisystem disorder with a good long-term prognosis. In its dozens of clinical features, those with independent prognostic value are still not well characterized. We retrospectively included 362 patients with newly diagnosed POEMS syndrome at our institute from 2000 to 2015. On the basis of a randomized sample splitting, we first identified four baseline clinical variables, including age >50 years (hazards ratio (HR) 4.07, 95% confidence interval (CI) 1.41-11.76, P=0.009), pulmonary hypertension (HR 3.99, 95% CI 1.44-11.04, P=0.008), pleural effusion (HR 3.81, 95% CI 1.23-11.79, P=0.02) and estimated glomerular filtration rate <30 ml/min/1.73 m (HR 8.25, 95% CI 2.18-31.25, P=0.002), associated with inferior overall survival in the derivation cohort, with the use of multivariate Cox regression model. These factors were incorporated together to develop a prognostic nomogram. Concordance index calculation (0.727, 95% CI 0.601-0.853, P=0.018) and calibration curve plotting demonstrated its significant predictive and discriminatory capacity in the validation cohort. This nomogram could be a useful and convenient tool in clinical practice to evaluate individualized prognosis in patients with newly diagnosed POEMS syndrome.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare plasma dyscrasia without standard treatment. This phase II prospective trial evaluates the safety and response of 12 cycles of low dose lenalidomide (10 mg) plus dexamethasone (Rdex) in patients with newly diagnosed POEMS syndrome. Forty-one patients (28 men) were enrolled and the median age at diagnosis was 49 years (range, 21-70 years). Twenty-one patients (46%) achieved complete hematologic response and the neurologic response rate was 95%. The median serum vascular endothelial growth factor (VEGF) declined from 5155 pg/mL (range, 534-14 328 pg/mL) to 832 pg/mL (95-6254 pg/mL) after therapy. The overall VEGF response rate was 83%, and the median time to response was 2 months, with a mean VEGF reduction of 43% at the first month. In terms of clinical response, Rdex substantially relieved extravascular volume overload, organomegaly, and pulmonary hypertension. No treatment-related deaths occurred and no patients suffered from lenalidomide-related grade 3 or above adverse events. After a median follow-up of 34 months, median overall survival (OS) and progression-free survival (PFS) were not reached, with an estimated 3-year OS and PFS of 90% and 75%, respectively. In conclusion, Rdex was active with high hematologic, VEGF and organ response rate and well tolerated for patients with newly diagnosed POEMS syndrome. This trial was registered at www.clinicaltrials.gov as #NCT01816620.

No abstract

Steroids hormones possess two distinct actions, a delayed genomic effect and a rapid non-genomic effect. Rapid steroid-triggered signaling is mediated by specific receptors localized most often to the plasma membrane. The nature of these receptors is of great interest and accumulated data suggest that G protein-coupled receptors (GPCRs) are appealing candidates. Increasing evidence regarding the interaction between steroids and specific membrane proteins, as well as the involvement of G protein and corresponding downstream signaling, have led to identification of physiologically relevant GPCRs as steroid extranuclear receptors. Examples include G protein-coupled receptor 30 (GPR30) for estrogen, membrane progestin receptor for progesterone, G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) for androgen, and trace amine associated receptor 1 (TAAR1) for thyroid hormone. These receptor-mediated biological effects have been extended to reproductive development, cardiovascular function, neuroendocrinology and cancer pathophysiology. However, although great progress have been achieved, there are still important questions that need to be answered, including the identities of GPCRs responsible for the remaining steroids (e.g., glucocorticoid), the structural basis of steroids and GPCRs’ interaction and the integration of extranuclear and nuclear signaling to the final physiological function. Here, we reviewed the several significant developments in this field and highlighted a hypothesis that attempts to explain the general interaction between steroids and GPCRs.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is a rare plasma cell dyscrasia sometimes treated with a haematopoietic cell autotransplant. We analyzed data from 138 subjects with newly diagnosed POEMS syndrome receiving a autotransplant at our center. Thirty-two subjects with severe end-organ dysfunction ineligible for immediate autotransplant received pretransplant therapy, which made a subsequent autotransplant feasible. Pretransplant therapy resulted in vascular endothelial growth factor (VEGF) remissions in 15 (47%). Thirty-three transplant recipients (24%) had early posttransplant complications. Risk factors for these complications identified through multivariate analysis included age >50 years (odds ratio (OR) 2.79, 95% confidence interval (CI) 1.09-7.14; P=0.033), time from symptom onset to transplant >5 years (OR 4.71, 95% CI 1.10-20.18; P=0.037) and pleural effusion (OR 3.39, 95% CI 1.26-9.12; P=0.016). Subjects receiving pretransplant therapy had fewer early complications than those who did not (OR 0.17, 95% CI 0.04-0.71; P=0.015), especially in subjects with a VEGF remission (OR 0.05, 95% CI 0.01-0.49; P=0.010). Autotransplants resulted in hematological remission in 60 (50%), VEGF remissions in 76 (72%) and improvements in other organ functions (65-90%). The 5-year progression-free survival (PFS) and overall survival were 76% (95% CI 64-84%) and 94% (95% CI 87-97%), respectively. Hematological (5-year PFS 83 vs 66%, P=0.008), VEGF (5-year PFS 79 vs 57%, P=0.021) remissions and especially both (5-year PFS 95 vs 61%, P=0.004) were associated with better PFS.

Renal impairment is a common complication of POEMS syndrome, but can be reversed with effective therapy in most cases.

Summary. Background: Direct oral anticoagulants have been evaluated for their efficacy and safety in the treatment of venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism. The randomized, double-blind Hokusai-VTE trial demonstrated that 60 mg of edoxaban once daily following initial heparin treatment is non-inferior to heparin overlapped with and followed by warfarin for the treatment of VTE, and is associated with significantly fewer bleeding events. Objectives: To assess the efficacy and safety of edoxaban versus warfarin among East Asian patients enrolled in the Hokusai-VTE trial. Patients/methods: The Hokusai-VTE trial enrolled 8292 patients from 439 centers worldwide, including 1109 patients from Japan, China, Korea, and Taiwan. The primary efficacy and safety outcomes were symptomatic recurrent VTE and clinically relevant bleeding, respectively. Results: In the overall East Asian population, the primary efficacy outcome of symptomatic recurrent VTE occurred in 16 of 563 (2.8%) patients in the edoxaban group versus 24 of 538 (4.5%) patients in the warfarin group (hazard ratio[HR] 0.64; 95% confidence interval [CI] 0.34-1.19; P = 0.1601). The primary safety outcome of clinically relevant bleeding occurred in 56 of 563 (9.9%) patients in the edoxaban group versus 93 of 538 (17.3%) patients in the warfarin group (HR 0.56; 95% CI 0.40-0.78; P < 0.001). Conclusions: Edoxaban is an effective and safer alternative to warfarin in East Asian patients with acute VTE who require anticoagulant therapy, consistent with overall study findings from the Hokusai-VTE trial.