Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.     

Ulcer of the tongue as a presenting feature of pulmonary tuberculosis

Oral tuberculosis is very rare and when present they are usually secondary to pulmonary tuberculosis. Tuberculous lesions of the tongue have become so infrequent that they are virtually a forgotten disease entity and may pose a diagnostic problem. The case reported in this paper emphasizes the importance of including tuberculosis in the differential diagnosis of any chronic oral ulcer. The low number of oral infections by M. tuberculosis could be due to underreporting.     

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191–201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 μM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 μM PAN-811 (an optimal neuroprotective concentration) for 1 h, 4 h, or 24 h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.     

Safety,tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30–60 IU) or oral zonisamide (4–25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.     

Loop myopexy with true muscle transplantation for very large angle heavy eye syndrome patient

A 42-year-old man presenting with complaints of squint for last 20 years. His visual acuity was 20/400 in right eye (RE) and 20/30 in left eye (LE) with glasses. His refraction was RE -16.75/-2.5 D cycl 180 and LE was -14.5/-1.5 D cycl 180. His axial length was 31.23 mm In RE and 29.72 mm in LE. On examination we found he had RE large esotropia with hypotropia measuring 130 pd base out and 40 pd base up in RE. A computerized tomography scan revealed that the superior rectus (SR) was shifted nasally, and lateral rectus (LR) was shifted inferiorly. A RE medial rectus (MR) recession and LR resection with muscle transplantation on the MR was done. A loop myopexy was done to correct the path of the LR and SR. The patient had only 18 pd eso and 20 pd hypo on follow-up after 3 months. Loop myopexy in conjunction with muscle transplantation is a safe and effective procedure for large angle esotropia associated with heavy eye syndrome.     

Antihypertensive effect of rhizome part of Acorus calamus on renal artery occlusion induced hypertension in rats

ObjectiveThe rhizomes part of Acorus calamus (AC) having the calcium inhibitory effect and diuretic activity which may potentiate Na+ excretion in hypertension induced by occlusion of renal artery. Therefore this study was aimed to investigate the effect of AC on experimentally induced hypertension.MethodsHypertension in rats was induced by clamping the left renal artery for 4h by arterial clamp (2K1C). At the end of experiment animal were anesthetized with ketamine (50 mg/kg). Carotid artery was cannulated which was connected to pressure transducer for estimation of blood pressure.ResultsEthyl acetate extract of Acorus calamus rhizomes (EAAC) treated rats that underwent hypertension, demonstrated significant (P < 0.01) lower systolic blood pressure and diastolic blood pressure when compared with 2K1C rats indicated blood pressure lowering activity. Plasma renin activity was significantly (P < 0.05) decreased in EAAC treated rats compared to 2K1C rats. EAAC treated rats that underwent hypertension demonstrated significant (P < 0.01) lower mean blood urea nitrogen and creatinine when compared with 2K1C rats. Lipid peroxidation was significantly (P < 0.001) decreased, where as nitric oxide level in tissue was significantly elevated in EAAC treated rats. Antioxidant enzymes like glutathione, superoxide dismutase and catalase were significantly (P < 0.05, P < 0.01, P < 0.001) increased in EAAC treated rats when compared to 2K1C rats.ConclusionsIn conclusions, EAAC treatment attenuated renal artery occlusion induced hypertension via nitric oxide generation and decreases the plasma renin activity.     

Changes in Apoptotic Mechanisms Following Penetrating Ballistic-Like Brain Injury

We investigated apoptotic pathways in a model of severe traumatic brain injury, penetrating ballistic-like brain injury (PBBI). TUNEL staining identified increasing apoptosis within 24 h. From targeted arrays, 11 genes were identified for temporal mRNA evaluation. In addition, mRNA levels and enzyme activity for caspases 3, 8, and 9 were examined. In the death receptor-mediated apoptosis pathway, the relative quantities (RQs) of mRNA for tnfr1, fas, and tnf were upregulated while trail mRNA was downregulated. In the anti-apoptotic TNF-R2 pathway, tnfr2 and flip were upregulated while xiap was downregulated. These findings indicate that increases in tnf levels following injury are not only pro-apoptotic but may also signal competing anti-apoptotic mechanisms. For the mitochondria-mediated apoptosis pathway, RQs of anti-apoptotic factors bcl2a1d and birc3 were upregulated while both bcl2 and bax were downregulated. RQs for casp 3 and casp 8 increased while casp9 decreased. Enzymatic activity increased for caspases 3, 8, and 9. While multiple mechanisms promoting and inhibiting apoptosis are at play during the first week after a PBBI, the cumulative result remains increased apoptosis. The ability to understand and dissect these events will assist in the development and evaluation of treatments targeting apoptosis following severe brain injury.