Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

BACKGROUND:

The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non‐Hodgkin lymphoma (HG‐NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced‐intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date.

METHODS:

PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG‐NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n = 41) or alternative donors (n = 39).

RESULTS:

At the time of the last follow‐up, 48 patients were alive (60%), and 32 had died. The 3‐year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET‐negative patients (25% vs 56%; P = .007), but there was no significant difference between the patients with or without chronic graft‐versus‐host disease (P = .400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3‐year overall survival (76% vs 33%; P = .001) and 3‐year progression‐free survival (73% vs 31%; P = .001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling).

CONCLUSIONS:

The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting. Cancer 2010. © 2010 American Cancer Society.     

Log Odds of Positive Lymph Nodes (LODDS): What Are Their Role in the Prognostic Assessment of Gastric Adenocarcinoma?

Background

Nodal status is an important prognostic factor for patients with gastric cancer. Log odds of positive nodes (LODDS) (log of the ratio between the number of positive nodes and the number of negative nodes) are a new effective indicator of prognosis. The aim of the study is to evaluate if LODDS are superior to N stage and lymph nodal ratio (LNR).

Methods

Prognostic efficacy of pN, nodal ratio, and LODDS was analyzed and compared in a group of 177 patients with gastric adenocarcinoma who underwent curative gastrectomy.

Results

pT, pN, LNR, and LODDS were all significantly correlated with 5-year survival. Multivariate analyses showed significant values as prognostic factor for pN, LNR, and LODDS. A Pearson test demonstrated no significant correlation between LODDS and retrieved nodes. In patients with less than 15 examined nodes, LODDS classification and pN were significantly correlated with survival, whereas LNR classification was not significantly related.

Conclusions

LODDS are not correlated with the extension of the lymphadenectomy and are able to predict survival even if less than 15 nodes are examined. They permit an effective prognostic stratification of patients with a nodal ratio approaching 0 and 1. Further studies are needed to clarify their role and if they are capable of guaranteeing some advantages over pN and LNR.     

Patients with cam-type femoroacetabular impingement demonstrate increased change in bone-to-bone distance during walking: A dual fluoroscopy study

Cam-type femoroacetabular impingement (FAI) syndrome is a painful, structural hip disorder. Herein, we investigated hip joint mechanics through in vivo, dynamic measurement of the bone-to-bone distance between the femoral head and acetabulum in patients with cam FAI syndrome and morphologically screened controls. We hypothesized that individuals with cam FAI syndrome would have larger changes in bone-to-bone distance compared to the control group, which we would interpret as altered joint mechanics as signified by greater movement of the femoral head as it articulates within the acetabulum. Seven patients with cam FAI syndrome and 11 asymptomatic individuals with typical morphology underwent dual fluoroscopy imaging during level and inclined walking (upward slope). The change in bone-to-bone distance between femoral and acetabular bone surfaces was evaluated for five anatomical regions of the acetabulum at each timepoint of gait. Linear regression analysis of the bone-to-bone distance considered two within-subject factors (activity and region) and one between-subjects factor (group). Across activities, the change in minimum bone-to-bone distance was 1.38–2.54 mm for the cam FAI group and 1.16–1.84 mm for controls. In all regions except the anterior–superior region, the change in bone-to-bone distance was larger in the cam group than the control group (p ≤ 0.024). An effect of activity was detected only in the posterior–superior region where larger changes were noted during level walking than incline walking. Statement of clinical significance: Patients with cam FAI syndrome exhibit altered hip joint mechanics during the low-demand activity of walking; these alterations could affect load transmission, and contribute to pain, tissue damage, and osteoarthritis.     

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background

Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability.

Objective

We sought to characterize the role of EIF4A2 variants in dystonic conditions.

Methods

We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts.

Results

We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees.

Conclusions

Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.