The syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia. Report of a new family and a review

A new autosomal recessive syndrome of chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anaemia (CDA) with microcytosis has recently been described in four children (two sibships) of one consangineous Arab family. In this report, we describe the clinical features and course of the syndrome of CRMO and CDA in two additional patients (one sibship) from another consanguineous Arab family and review the literature. The two patients (brother and sister), the products of a consanguineous marriage, developed the syndrome at an early age of 3 weeks and 2 months respectively. The diagnosis of CRMO was confirmed by radiological and technetium isotope bone scans. Bone marrow studies confirmed the diagnosis of CDA. Peripheral blood films showed hypochromia and microcytosis. The sites involved by CRMO were periarticular, mainly around the elbow, knee, wrist and small joints of the hand. The brother is now 21 years old and the sister 3.5 years old and CRMO is still active with frequent relapses. The brother developed flexion deformities at the age of 13 years. Both patients failed to thrive; weight and height were below the 5th percentile. CONCLUSION: This is the second report of the syndrome of chronic recurrent multifocal osteomyelitis and microcytic congenital dyserythropoietic anaemia, confirming it as a clinical entity, inherited as an autosomal recessive trait. The disease is characterised by an early onset, long clinical course of remissions and relapses, and seems to be different from the sporadic form of chronic recurrent multifocal osteomyelitis.     

Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction

Prior studies demonstrated the association between the major adverse cardiovascular outcomes and both higher platelet and lower lymphocyte counts. Our study explores the value of the platelet/lymphocyte ratio (PLR) as a marker of long-term mortality in patients presented with non-ST segment elevation myocardial infarction (NSTEMI). This is an observational study with a total 619 NSTEMI patients admitted to a tertiary center between 2004 and 2006. Patients were stratified into equal tertiles according to their admission PLR. The primary outcome, 4?year all-cause mortality, was compared among the PLR tertiles. The first, second and third PLR tertiles were PLR??176, respectively) included 206, 206 and 207 patients, respectively. There was a significant higher 4?year all-cause mortality in the higher PLR tertiles (the mortalities were 17, 23 and 42?% for the first, second and third PLR tertiles respectively, p??176, patients with dual antiplatelet therapy had lower mortality versus those with mono-platelet therapy. Further studies are needed to clarify these findings.     

Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases

Background

Orthotopic liver transplantation (LT) in non-alcoholic steatohepatitis (NASH) is increasing in parallel with the obesity epidemic.

Methods

This study retrospectively reviewed the clinical outcomes of LTs in NASH (n= 129) and non-NASH (n= 775) aetiologies carried out at a single centre between 1999 and 2009.

Results

Rates of 1-, 3- and 5-year overall survival in NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P= 0.04). Compared with non-NASH patients, post-LT mortality in NASH patients was more commonly caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05) aetiologies. Five-year survival was lower in NASH patients with a high-risk phenotype (age >60 years, body mass index >30 kg/m², with hypertension and diabetes) than in NASH patients without these characteristics (72% vs. 87%; P= 0.02). Subgroup analyses revealed that 5-year overall survival in NASH was equivalent to that in Laennec''s cirrhosis (85% vs. 80%; P= 0.87), but lower than that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P= 0.04).

Conclusions

Orthotopic LT in NASH was associated with increased early postoperative mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those in non-NASH patients.     

CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes

Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve post-transplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy after alloSCT.Adults with MDS or AML in morphologic complete remission at CC-486 initiation (42 to 84 days after alloSCT) were included. Patients received 1 of 4 CC-486 dosing schedules per 28-day cycle for up to 12 cycles. Endpoints included safety, pharmacokinetics, graft-versus-host disease (GVHD) incidence, relapse/progression rate, and survival.Of 30 patients, 7 received CC-486 once daily for 7 days per cycle (200 mg, n?=?3; 300 mg, n?=?4) and 23 for 14 days per cycle (150 mg, n?=?4; 200 mg, n?=?19 [expansion cohort]). Grades 3 to 4 adverse events were infrequent and occurred with similar frequency across regimens. Standard concomitant medications did not alter CC-486 pharmacokinetic parameters. Three patients (10%) experienced grade III acute GVHD and 9 experienced chronic GVHD. Of 28 evaluable patients, 6 (21%) relapsed or had progressive disease: 3 of 7 patients (43%) who had received 7-day dosing and 3 of 23 (13%) who had received 14-day dosing. Transplant-related mortality was 3%. At 19 months of follow-up, median overall survival was not reached. Estimated 1-year survival rates were 86% and 81% in the 7-day and 14-day dosing cohorts, respectively.CC-486 maintenance was generally well tolerated, with low rates of relapse, disease progression, and GVHD. CC-486 maintenance may permit epigenetic manipulation of the alloreactive response postallograft. Findings require confirmation in randomized trials. (ClinicalTrials.gov NCT01835587.)     

Mid- to long-term results of total lumbar disc replacement: a prospective analysis with 5- to 10-year follow-up

Background contextThe role of fusion of lumbar motion segments for the treatment of intractable low back pain (LBP) from degenerative disc disease (DDD) without deformities or instabilities remains controversially debated. Total lumbar disc replacement (TDR) has been used as an alternative in a highly selected patient cohort. However, the amount of long-term follow-up (FU) data on TDR is limited. In the United States, insurers have refused to reimburse surgeons for TDRs for fear of delayed complications, revisions, and unknown secondary costs, leading to a drastic decline in TDR numbers.PurposeTo assess the mid- and long-term clinical efficacy as well as patient safety of TDR in terms of perioperative complication and reoperation rates.Study design/settingProspective, single-center clinical investigation of TDR with ProDisc II (Synthes, Paoli, PA, USA) for the treatment of LBP from lumbar DDD that has proven unresponsive to conservative therapy.Patient samplePatients with a minimum of 5-year FU after TDR, performed for the treatment of intractable and predominant (≥80%) axial LBP resulting from DDD without any deformities or instabilities.Outcome measuresVisual analog scale (VAS), Oswestry Disability Index (ODI), and patient satisfaction rates (three-scale outcome rating); complication and reoperation rates as well as elapsed time until revision surgery; patient's professional activity/employment status.MethodsClinical outcome scores were acquired within the framework of an ongoing prospective clinical trial. Patients were examined preoperatively, 3, 6, and 12 months postoperatively, annually from then onward. The data acquisition was performed by members of the clinic's spine unit including medical staff, research assistants, and research nurses who were not involved in the process of pre- or postoperative decision-making.ResultsThe initial cohort consisted of 201 patients; 181 patients were available for final FU, resembling a 90.0% FU rate after a mean FU of 7.4 years (range 5.0–10.8 years). The overall results revealed a highly significant improvement from baseline VAS and ODI levels at all postoperative FU stages (p<.0001). VAS scores demonstrated a slight (from VAS 2.6 to 3.3) but statistically significant deterioration from 48 months onward (p<.05). Patient satisfaction rates remained stable throughout the entire postoperative course, with 63.6% of patients reporting a highly satisfactory or a satisfactory (22.7%) outcome, whereas 13.7% of patients were not satisfied. The overall complication rate was 14.4% (N=26/181). The incidence of revision surgeries for general and/or device-related complications was 7.2% (N=13/181). Two-level TDRs demonstrated a significant improvement of VAS and ODI scores in comparison to baseline levels (p<.05). Nevertheless, the results were significantly inferior in comparison to one-level cases and were associated with higher complication (11.9% vs. 27.6%; p=.03) and inferior satisfaction rates (p<.003).ConclusionsDespite the fact that the current data comprises the early experiences and learning curve associated with a new surgical technique, the results demonstrate satisfactory and maintained mid- to long-term clinical results after a mean FU of 7.4 years. Patient safety was proven with acceptable complication and reoperation rates. Fear of excessive late complications or reoperations following the primary TDR procedure cannot be substantiated with the present data. In carefully selected cases, TDR can be considered a viable treatment alternative to lumbar fusion for which spine communities around the world seem to have accepted mediocre clinical results as well as obvious and significant drawbacks.