A case-comparison study of pregnant women with mitochondrial disease - what to expect?

OBJECTIVE: Mitochondrial disease is a disorder of energy metabolism that affects 1 in 4300 adults in the UK. Pregnancy is associated with physiological demands that have implications for energy metabolism. We were interested to know how pregnancy was affected in women with mitochondrial disease, particularly those with the most common pathogenic mutation m.3243A>G. DESIGN: Retrospective case-comparison study. POPULATION/SETTING: Sixty-seven women with genetically confirmed mitochondrial disease from the UK Mitochondrial Diseases Cohort and 69 unaffected women participated. METHODS: Participants answered questionnaires regarding each of their pregnancies. Patients were divided into two groups according to genetic mutation, with those harbouring m.3243A>G comprising a single group. MAIN OUTCOME MEASURES: Pregnancy-related complications, mode of delivery, gestational age and birthweight of newborns. RESULTS: Of 139 live births in the comparison group, 62 were in the m.3243A>G group and 87 were in the 'all other mutations' group. Pregnancies of women with the m.3243A>G mutation had significantly more gestational diabetes (odds ratio [OR] = 8.2, 95% CI 1.3-50.1), breathing difficulties (OR = 7.8, 95% CI 1.0-59.1) and hypertension (OR = 8.2, 95% CI 3.1-21.5) than the comparison group. Only half of the pregnancies in the m.3243A>G group had normal vaginal delivery, with emergency caesarean section accounting for 24.2% of deliveries. Babies were born significantly earlier to mothers harbouring m.3243A>G with 53.3% of them preterm (<37 weeks). These babies were also more likely to require resuscitation and admission. CONCLUSION: Women who carried the m.3243A>G mutation appeared to be at higher risk of complications during pregnancies, caesarean section and preterm delivery than the unaffected women or those with other forms of mitochondrial disease. TWEETABLE ABSTRACT: Pregnant women with mitochondrial disease - m.3243A>G mutation - are at greatly increased risk of complications and preterm delivery.

Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant.

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.

Relations between anxiety sensitivity and dimensions of alexithymia in a young adult sample.

This study was conducted to assess the relations between anxiety sensitivity (AS) and dimensions of alexithymia in a nonclinical sample. We also sought to determine whether these relations persist after controlling for trait anxiety levels and panic attack history, and after controlling for item redundancy between the Anxiety Sensitivity Index (ASI) and the 20-item Toronto Alexithymia Scale (TAS-20). A sample of 238 undergraduate students completed the ASI, the TAS-20, and measures of trait anxiety and panic. A group of high AS participants (n=36) was found to have a significantly higher TAS-20 total score than a group of low AS participants (n=41), both before and after conceptually redundant TAS-20 items were removed. ASI scores were found to be significantly positively correlated with scores on the two TAS-20 subscales suspected of sharing a functional relation with AS (i.e., difficulty identifying emotions; difficulty describing emotions), whereas ASI scores were not significantly correlated with scores on the TAS-20 subscale believed to be functionally unrelated to AS (i.e., external-oriented thinking). This pattern of correlations between ASI scores and alexithymia dimensions persisted following the removal of conceptually redundant TAS-20 items, suggesting that the relation between AS and alexithymia is not merely an artifact of item redundancy. ASI scores remained significantly correlated with scores on the TAS-20's difficulty identifying emotions subscale, and marginally correlated with scores on the TAS-20's difficulty describing emotions subscale, after accounting for the influences of trait anxiety and panic history. The results also revealed that individuals who both experience frequent anxiety and who greatly fear their anxiety symptoms report the greatest difficulties identifying and describing emotional states. Implications for understanding the alexithymia construct, as well as potential clinical implications of the findings, are discussed.

Three years' experience with home peritoneal dialysis.

Our results to date indicate that home peritoneal dialysis is a sucessful, safe, and simple dialysis treatment which is accessible to virtually all patients who require chronic dialysis treatment.

The permanent Tenckhoff catheter for chronic peritoneal dialysis.

Over a 3 1/2-year period the permanent Tenckhoff catheter was used in 66 patients (32 men and 34 women) maintained on chronic peritoneal dialysis for periods from 2 1/2 to 36 1/2 months; 57 patients had dialysis in hospital for 20 to 24 hours twice a week and the other 9 had dialysis at home for 10 to 12 hours four times a week. While the Tenckhoff catheter was in place 14 patients received a renal transplant; for 13 who required peritoneal dialysis during the post-transplant phase the Tenckhoff catheter was used. In nine patients abdominal surgery did not interfere with the continuation of peritoneal dialysis via the Tenckhoff catheter. From a total of 5067 dialyses 40 positive cultures were reported (0.8%). Peritonitis was clinically evident on only 14 occasions (0.28%). Permanent catheter obstruction developed in 16 patients, in 11 of whom it was related to peritonitis. With the introduction of the permanent Tenckhoff catheter long-term peritoneal dialysis has become a simple, safe and painless procedure, suitable for virtually all patients who require maintenance dialysis.