Clinical cardiac involvement in thrombotic thrombocytopenic purpura: a systematic review

BACKGROUND: Autopsy studies consistently demonstrate cardiac involvement in thrombotic thrombocytopenic purpura (TTP), but clinical evidence for cardiac abnormalities is rarely reported. STUDY DESIGN AND METHODS: This systematic review addresses the apparent discrepancy between autopsy and clinical data. English language articles were identified by keywords for both TTP and for cardiac symptoms, testing, or events. Patients were analyzed if they were more than 10 years old with idiopathic TTP. RESULTS: Thirty articles were identified that described 111 eligible patients: 20 case reports described 27 patients, 9 retrospective cohort studies described 74 patients, and 1 prospective cohort study described 10 patients. Cardiac events included infarction (26 patients), congestive failure (17), arrhythmias (10), cardiogenic shock (6), and sudden cardiac death (8). Mortality was assessed in 101 patients: 55 died, and 48 autopsies were described. All demonstrated cardiac microvascular thrombi, hemorrhage, and/or necrosis. Follow-up information was reported in only 6 of the 16 patients who survived a cardiac event (follow-up duration, 10 days-2 years; median, 7 weeks). CONCLUSIONS: The frequency and sequelae of clinical cardiac abnormalities in TTP cannot be accurately assessed because most patients were described in reports of few selected patients; many patients were reported before the availability of effective treatment for TTP and sensitive tests for cardiac involvement. Continuing case reports and cohort studies, however, suggest that cardiac abnormalities may be important and often unrecognized causes of mortality and morbidity in patients with TTP. Prospective studies are needed to determine if cardiac therapy can improve survival and long-term outcomes of patients with TTP.     

Modified Sofield-Millar operation: less invasive surgery of lower limbs in osteogenesis imperfecta

We present the results of intramedullary rodding of long bones of the lower limbs in children with osteogenesis imperfecta using a modified Sofield-Millar operation. Fourteen patients (mean age at primary operation was 5 years 11 months) were treated with a modified Sofield-Millar operation which allows minimal bone exposure, preservation of the periosteum and keeping the number of osteotomies to the minimum. Union was achieved in all cases within 7 weeks. Of the 14 patients (29 bones) treated with nonelongating rods, rod revisions were needed in 13 patients (26 bones). We found no statistically significant difference between the width of the bone immediately postoperatively and at the final follow-up. The walking ability was improved in four patients. Advantages of less invasive surgery in osteogenesis imperfecta are rapid bone union, no bone atrophy or nonunion, better postoperative mobility and small scars.

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Résumé  L’objectif de cette étude est d’évaluer les résultats du brochage intra médullaire des os longs des membres inférieurs chez les enfants présentant une ostéogénèse imparfaite en utilisant la technique modifiée de Sofield-Millar. Matériel et méthode : 14 patients (age moyen à la première intervention 5 ans) ont été traités avec cette méthode de Sofield-Millar modifiée qui permet, à partir d’un abord minimal de préserver le périoste; de réduire au minimum le nombre d’ostéotomies. Résultats, une consolidation a été obtenue dans tous les cas au bout de sept semaines. 14 patients (29 segments osseux) ont été traités avec un clou ne permettant pas la croissance, la révision du clou a été nécessaire chez 13 patients (26 segments osseux). Nous n’avons pas trouvé de différences significatives sur la qualité osseuse en post-op immédiat et au suivi final. La marche a été améliorée chez 4 patients. En conclusion : cette technique moins invasive est avantageuse dans le traitement de l’ostéogénèse imparfaite et permet une consolidation rapide sans atrophie osseuse et sans pseudarthrose avec une bonne mobilité post-opératoire et des cicatrices minimes.

     

Drosophila Nora virus capsid proteins differ from those of other picorna-like viruses

The recently discovered Nora virus from Drosophila melanogaster is a single-stranded RNA virus. Its published genomic sequence encodes a typical picorna-like cassette of replicative enzymes, but no capsid proteins similar to those in other picorna-like viruses. We have now done additional sequencing at the termini of the viral genome, extending it by 455 nucleotides at the 5' end, but no more coding sequence was found. The completeness of the final 12,333-nucleotide sequence was verified by the production of infectious virus from the cloned genome. To identify the capsid proteins, we purified Nora virus particles and analyzed their proteins by mass spectrometry. Our results show that the capsid is built from three major proteins, VP4A, B and C, encoded in the fourth open reading frame of the viral genome. The viral particles also contain traces of a protein from the third open reading frame, VP3. VP4A and B are not closely related to other picorna-like virus capsid proteins in sequence, but may form similar jelly roll folds. VP4C differs from the others and is predicted to have an essentially α-helical conformation. In a related virus, identified from EST database sequences from Nasonia parasitoid wasps, VP4C is encoded in a separate open reading frame, separated from VP4A and B by a frame-shift. This opens a possibility that VP4C is produced in non-equimolar quantities. Altogether, our results suggest that the Nora virus capsid has a different protein organization compared to the order Picornavirales.     

Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer

Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels.     

The use of light/chemically hardened polymethylmethacrylate, polyhydroxyethylmethacrylate, and calcium hydroxide graft material in combination with polyanhydride around implants in minipigs: part I: immediate stability and function

Background: The present study is designed as a proof‐of‐concept study to evaluate light/chemical hardening technology and a newly formulated polymethylmethacrylate, polyhydroxyethylmethacrylate, and calcium hydroxide (PPCH) plus polyanhydride (PA) (PPCH‐PA) composite graft material as a bone substitute compared to positive and negative controls in a minipig model. Methods: PPCH‐PA (composite graft); PPCH alone (positive control), PA alone (positive control), and no graft (negative control) were compared. Four mandibular premolar teeth per quadrant were extracted; a total of 48 implants were placed into sockets in three minipigs. Abutments were placed protruding into the oral cavity 4 mm in height for immediate loading. Crestal areas and intrabony spaces were filled with PPCH‐PA, PPCH, or PA using a three‐phase delivery system in which all graft materials were hardened by a light cure. In the negative control group, implant sites were left untreated. At 12 weeks, block sections containing implants were obtained. Evaluations included periodontal probing, pullout‐force load, and stability measurements to determine implant stability, radiographs to examine bone levels, and scanning electron microscopy (SEM)–energy‐dispersed spectroscopy to determine bone‐to‐implant contact. Results: Probing measurements did not reveal any pathologic pocket formation or bone loss. Radiographs revealed that immediate implant placement and loading resulted in bone at or slightly apical to the first thread of the implant in all groups at 12 weeks. Stability test values showed a relative clinical stability for all implants (range: ?7 to +1); however, implants augmented with PPCH‐PA exhibited a statistically significantly greater stability compared to all other groups (P <0.05). The newly formed bone in PPCH‐PA–treated sites was well organized with less marrow spaces and well‐distributed osteocytes. SEM revealed a tighter implant–socket interface in the PPCH‐PA group compared to other groups with reduced microfissures and implant–bone interface fractures during pullout testing, whereas implants treated with PA or no graft showed ≈10‐μm microfissures between the implant and bone with fractures of the intrathread bone. Conclusions: The newly formulated chemically hardened graft material PPCH‐PA was useful in immediate implant placement after tooth extraction and resulted in greater stability and a well‐organized implant–bone interface with immediate loading, especially in those areas where cancellous bone was present. The results of this proof‐of‐concept study warranted further research investigating different healing times and longer durations.