Outcomes of transplantation using organs from a donor infected with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase (KPC)‐producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC‐producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC‐producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC‐producing K. pneumoniae. All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.     

Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study

Aim: Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone on vascular inflammation, oxidant stress, ambulatory blood pressure (BP) and other atherosclerotic factors in patients with the metabolic syndrome. Methods: This is a randomized, double blind, placebo‐controlled study in 53 subjects with the metabolic syndrome. Participants were randomized to simvastatin 40 mg/day plus placebo vs. simvastatin 40 mg/day plus rosiglitazone 4 mg/day for 6 months. The primary endpoint was the between‐group difference in high‐sensitivity C‐reactive protein (hs‐CRP) and secondary variables including urinary isoprostanes, serum malondialdehyde (MDA), ambulatory BP, adiponectin, and lipid and glycaemic profiles. Results: At study end, the group randomized to the simvastatin/rosiglitazone combination had a greater reduction in hs‐CRP of 1.33 mg/dl, (p = 0.029) and showed a trend for a greater reduction in urinary isoprostane (?39%), (p = 0.056) compared to simvastatin/placebo group. Changes in MDA levels did not differed between groups (p = 0.81). 24‐h systolic blood pressure (SBP) also showed a 4.5 mmHg reduction at 6 months (p = 0.06). Adiponectin levels increased by 3.91 µg/ml in the combination group over placebo, (p = 0.03) and blood glucose decreased in combination group vs. placebo. Conclusion: Our data show that patients with the metabolic syndrome given a statin/TZD combination manifest greater reductions in markers of vascular inflammation and oxidant stress, 24‐h ambulatory BP and increases in adiponectin as well as improved glycaemic indices.     

Improving survival during heart transplantation: diagnosis of antibody-mediated rejection and techniques for the prevention of graft injury

The diagnosis of antibody-mediated rejection (AMR) has presented a challenge due to the pleiomorphic immunologic responses that represent the condition. A consensus with regard to its pathological diagnosis continues to evolve. Due to an increasing number of sensitized patients undergoing heart transplantation, its incidence appears to be on the rise and the condition is associated with worse outcomes than acute cellular rejection. Treatment of AMR is also more difficult and response to increases in conventional immunosuppression is often limited. Risk factors for AMR include the use of ventricular assist devices, prior exposure to blood products, allografts and multiparity. Detection of alloantibodies with a high specificity and sensitivity allows risk stratification of recipients at potential risk of AMR. Desensitization and AMR treatment strategies are focused on several therapeutic targets, including suppression of T and B cells and elimination or inhibition of circulating antibodies.     

Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population

Purpose  

Due to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB.     

Disease Expression and Familial Transmission of Fuchs Endothelial Corneal Dystrophy With and Without CTG18.1 Expansion

PurposeTo characterize inheritance, penetrance, and trinucleotide repeat expansion stability in Fuchs endothelial corneal dystrophy (FECD).MethodsOne thousand unrelated and related subjects with and without FECD were prospectively recruited. CTG18.1 repeat length (CTG18.1_L) was determined via short tandem repeat assay and Southern blotting of leukocyte DNA. Multivariable logistic regression and generalized estimating equation models were employed.ResultsThere were 546 unrelated FECD cases (67.6% female; 70 ± 10 years) and 235 controls (63.8% female; 73 ± 8 years; all ≥ 50 years). CTG18.1 expansion (CTG18.1exp+) was observed in 424 (77.7%) cases and 18 (7.7%) controls (P = 2.48 × 10^–44). CTG18.1 expansion was associated with FECD severity (P = 5.62 × 10^–7). The family arm of the study included 331 members from 112 FECD-affected families; 87 families were CTG18.1exp+. Autosomal dominant inheritance with variable expression of FECD was observed, regardless of expansion status. FECD penetrance of CTG18.1 expansion increased with age, ranging from 44.4% in the youngest (19–46 years) to 86.2% in the oldest (64–91 years) age quartiles. Among 62 parent–offspring transmissions of CTG18.1exp+, 48 (77.4%) had a change in CTG18.1_L ≤ 10 repeats, and eight (12.9%) were ≥50 repeats, including five large expansions (∼1000–2000 repeats) that contracted. Among 44 offspring who did not inherit the CTG18.1exp+ allele, eight (18.2%) exhibited FECD.ConclusionsCTG18.1 expansion was highly associated with FECD but demonstrated incomplete penetrance. CTG18.1_L instability occurred in a minority of parent–offspring transmissions, with large expansions exhibiting contraction. The observation of FECD without CTG18.1 expansion among family members in CTG18.1exp+ families highlights the complexity of the relationship between the FECD phenotype and CTG18.1 expansion.