Subclinical myocardial inflammation and diffuse fibrosis are common in systemic sclerosis – a clinical study using myocardial T1-mapping and extracellular volume quantification

Background

Systemic sclerosis (SSc) is characterised by multi-organ tissue fibrosis including the myocardium. Diffuse myocardial fibrosis can be detected non-invasively by T1 and extracellular volume (ECV) quantification, while focal myocardial inflammation and fibrosis may be detected by T2-weighted and late gadolinium enhancement (LGE), respectively, using cardiovascular magnetic resonance (CMR). We hypothesised that multiparametric CMR can detect subclinical myocardial involvement in patients with SSc.

Methods

19 SSc patients (18 female, mean age 55 ± 10 years) and 20 controls (19 female, mean age 56 ± 8 years) without overt cardiovascular disease underwent CMR at 1.5T, including cine, tagging, T1-mapping, T2-weighted, LGE imaging and ECV quantification.

Results

Focal fibrosis on LGE was found in 10 SSc patients (53%) but none of controls. SSc patients also had areas of myocardial oedema on T2-weighted imaging (median 13 vs. 0% in controls). SSc patients had significantly higher native myocardial T1 values (1007 ± 29 vs. 958 ± 20 ms, p < 0.001), larger areas of myocardial involvement by native T1 >990 ms (median 52 vs. 3% in controls) and expansion of ECV (35.4 ± 4.8 vs. 27.6 ± 2.5%, p < 0.001), likely representing a combination of low-grade inflammation and diffuse myocardial fibrosis. Regardless of any regional fibrosis, native T1 and ECV were significantly elevated in SSc and correlated with disease activity and severity. Although biventricular size and global function were preserved, there was impairment in the peak systolic circumferential strain (-16.8 ± 1.6 vs. -18.6 ± 1.0, p < 0.001) and peak diastolic strain rate (83 ± 26 vs. 114 ± 16 s-1, p < 0.001) in SSc, which inversely correlated with diffuse myocardial fibrosis indices.

Conclusions

Cardiac involvement is common in SSc even in the absence of cardiac symptoms, and includes chronic myocardial inflammation as well as focal and diffuse myocardial fibrosis. Myocardial abnormalities detected on CMR were associated with impaired strain parameters, as well as disease activity and severity in SSc patients. CMR may be useful in future in the study of treatments aimed at preventing or reducing adverse myocardial processes in SSc.     

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8-4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8-4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.     

Outcome Analysis of Fixed Angle Locking Plate in Patella Fractures: A Single Centre Experience from North India

BackgroundTension band wiring supposedly is the most commonly used technique for displaced patella fractures, but is not effective in comminuted fractures and osteoporotic bones. It often leads to loosening of wires, dislocation of fracture, hardware problem and failure of osteosynthesis, resulting in knee stiffness and post-traumatic osteoarthritis. The aim of the study is to evaluate clinical outcome in patients with acute patella fractures (< 3 week) treated with unidirectional angle fixed low-profile titanium patella locking plate.Materials and methodsTwenty patients who presented with displaced patella fractures, aged between 18–70 years were included in the study. All fractures were reduced and fixed with unidirectional angle fixed stable low-profile titanium patella locking plate. Knee Range of motion and Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL) was used to evaluate the outcome.ResultsWe were able to achieve union in 19 out of 20 patients. One patient with comminuted patella fracture had failure of fixation, which was revised. Mean flexion at final follow-up was 124° (110°–130°) and none of the patients had extensor lag. The final radiograph revealed complete union in all patients.ConclusionThis technique offers an option of fixation in comminuted patella fracture and in osteoporotic individuals. It provides mechanical stability for fracture fixation resulting in anatomical reduction, good functional outcome, lower incidence of symptomatic implant or failure of osteosynthesis.     

Plasmodium falciparum: Multidrug resistance

Malaria is the most lethal and debilitating disease caused by the protozoan parasite Plasmodium worldwide. The most severe forms of disease and the incidence rates of mortality are associated with P. falciparum infections. With the identification of disease source and symptoms, many chemical entities were developed naturally and synthetically for administration as a potential antimalarial drug. The major classes of approved antimalarial drugs that are governed as first‐line treatment in tropical and subtropical areas include quinolines, naphthoquinones, antifolates, 8‐aminoquinolines, and endoperoxides. However, the efficacy of antimalarial drugs has decreased due to ongoing multidrug resistance problem to current drugs. With increasing resistance to the current antimalarial artemisinin and its combination therapies, malaria prophylaxis has declined gradually. New‐generation antimalarial and novel drug target are required to check the incidence of malaria resistance. This review summarizes the emergence of multidrug resistance to known antimalarial and the development of new antimalarial to resolve drug resistance condition. Few essential proteins are also discussed that can be considered as novel drug target against malaria in future.     

Role of gut microbiota in cardiovascular diseases

The human gut is colonized by a community of microbiota, primarily bacteria,that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology.Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease(CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites,including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.     

益气固冲法对月经过多患者子宫内膜微环境的影响

目的:探讨益气固冲法治疗月经过多的临床疗效以及对子宫内膜微环境的影响.方法:将60例月经过多患者随机分为治疗组与对照组各30例,治疗组口服益气安冲汤治疗,对照组采用益宫宁血口服液治疗.观察治疗前后月经第2天子宫内膜生长因子(EGF)、血管内皮生长因子(VEGF);PGL2代谢产物(PGF1α)、血栓素TXA2代谢产物(TXB2)的情况.结果:治疗后治疗组与对照组比较,EGF、VEGF升高,PGF1α/TXB2显著降低,差异有统计学意义(P＜0.05).结论:益气固冲法可能通过改善血管舒缩障碍,促进血管生成,改善子宫内膜微环境从而有效缓解月经过多.     

Fibrosingmediastinitis and consequent superior vena cava syndrome - A case report

Fibrosing mediastinitis is a rare, chronic inflammatory disease that has several implicated etiologies. We describe a case of a 41-year old woman who presented with the classic signs and symptoms of superior vena cava syndrome. Imaging revealed a diffuse infiltrative mediastinal process, which on biopsy was consistent with fibrosing mediastintis.     

Global Collaborations for Cervical Cancer: Can the East–West Alliance Facilitate Treatment for all?

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low–middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low–middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy.     

Synthesis and biological evaluation of 18F-Norfallypride in the rodent brain using PET imaging

Norfallypride (N-[(2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3’-fluoropropyl)benzamide), an analog of fallypride, has been synthesized and evaluated as a potential PET imaging agent for dopamine receptors with increased subtype selectivity. In order to synthesize ¹⁸F-Norfallypride, the substituted benzamide tosylate (S)-N-[(1-BOC-2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3’-tosyloxypropyl)-benzamide) was radiolabeled with ¹⁸F using Kryptofix and K₂CO₃ in acetonitrile and deprotected with trifluoroacetic acid to yield (S)-¹⁸F-Norfallypride in approx. 10% radiochemical yields. Norfallypride exhibited an IC₅₀ of 0.63 μM for displacing ¹⁸F-fallypride in rat brain slices. In vitro rat brain autoradiographic studies revealed weak binding of ¹⁸F-norfallypride to striatal regions. PET imaging in rats showed low brain uptake of ¹⁸F-norfallypride in the rat brain. Ex vivo brain PET analysis displayed binding of ¹⁸F-norfallypride in several brain regions. With respect to the cerebellum, ex vivo PET ratios were: striatum > 3; hypothalamus > 2; hippocampus ~ 2; cerebellar nuclei > 2 while autoradiographic ratios were 14, 9, 4 and 6 respectively. ¹⁸F-Norfallypride exhibited a unique binding profile to rat brain regions known to contain significant amounts of dopamine D3 and serotonin 5HT₃ receptors. Efforts are currently under way to increase brain permeability and fully characterize the binding of ¹⁸F-norfallypride in vivo.