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  1. Sahota O, van Berkel D, Ong T, Drummond A, Hendrick P, Quraishi N, et al.
    Osteoporos Int, 2021 Apr;32(4):785-786.
    PMID: 33491138 DOI: 10.1007/s00198-021-05848-z
  2. Sahota O, Leighton P, Cameron M, Taylor R, Ong T, Drummond A, et al.
    Geriatr Orthop Surg Rehabil, 2021;12:21514593211026794.
    PMID: 34290898 DOI: 10.1177/21514593211026794
    Background: Pubic rami fragility fractures are common in older people and result in significant morbidity and increased mortality. Co-existing fractures of the sacrum are common, but routinely missed. The aim of the study was to explore the perceptions in the assessment and treatment of pubic rami and sacral fragility fractures amongst healthcare professionals.

    Methods: We interviewed 14 participants about their experience in the assessment and treatment of patients presenting with pubic rami fragility fractures. Data was analyzed using an inductive thematic approach.

    Results: The majority of patients presenting with a pubic rami fragility fracture were managed by geriatricians. However, many of the geriatricians were not aware that these fractures have a high association with co-existing sacral fragility fractures. Furthermore, they were not aware of the limitations of standard x-ray imaging, nor of the potential benefits of surgical intervention for sacral fragility fractures. Spinal surgeons recommended that early, more specialist imaging in patients with pubic rami fragility fractures failing to mobilize, would change clinical management, if found to have a coexisting sacral fragility fracture, amenable to surgical intervention.

    Conclusions: The awareness, assessment and management of sacral fragility fractures in patients presenting with pubic rami fragility fractures is poor amongst healthcare professionals in geriatric medicine. Spinal surgeons in this study advocate early further imaging and surgical intervention in patients confirmed to have a concomitant sacral fragility fracture who are failing to mobilize.

  3. Faisal T, Tan KY, Sim SM, Quraishi N, Tan NH, Tan CH
    J Proteomics, 2018 07 15;183:1-13.
    PMID: 29729992 DOI: 10.1016/j.jprot.2018.05.003
    The venom proteome of wild Pakistani Russell's viper (Daboia russelii) was investigated through nano-ESI-LCMS/MS of the reverse-phase HPLC fractions. A total of 54 venom proteins were identified and clustered into 11 protein families. Phospholipase A2 (PLA2, 63.8%) and Kunitz-type serine protease inhibitor (KSPI, 16.0%) were most abundant, followed by snake venom serine protease (SVSP, 5.5%, mainly Factor V activating enzyme), vascular endothelial growth factor (VEGF, 4.3%), snake venom metalloproteinase (SVMP, 2.5%, mainly Factor X activating enzyme) and phosphodiesterase (PDE, 2.5%). Other minor proteins include cysteine-rich secretory protein (CRiSP), snake venom C-type lectin/lectin-like protein (snaclec), nerve growth factor, L-amino acid oxidase and 5'-nucleotidase. PLA2, KSPI, SVSP, snaclec and SVMP are hemotoxic proteins in the venom. The study indicated substantial venom variation in D. russelii venoms of different locales, including 3 Pakistani specimens kept in the USA. The venom exhibited potent procoagulant activity on human plasma (minimum clotting dose = 14.5 ng/ml) and high lethality (rodent LD50 = 0.19 μg/g) but lacked hemorrhagic effect locally. The Indian VINS Polyvalent Antivenom bound the venom immunologically in a concentration-dependent manner. It moderately neutralized the venom procoagulant and lethal effects (normalized potency against lethality = 2.7 mg venom neutralized per g antivenom).

    BIOLOGICAL SIGNIFICANCE: Comprehensive venom proteomes of D. russelii from different locales will facilitate better understanding of the geographical variability of the venom in both qualitative and quantitative terms. This is essential to provide scientific basis for the interpretation of differences in the clinical presentation of Russell's viper envenomation. The study revealed a unique venom proteome of the Pakistani D. russelii from the wild (Indus Delta), in which PLA2 predominated (~60% of total venom proteins). The finding unveiled remarkable differences in the venom compositions between the wild (present study) and the captive specimens reported previously. The integration of toxicity tests enabled the correlation of the venom proteome with the envenoming pathophysiology, where the venom showed potent lethality mediated through coagulopathic activity. The Indian VINS Polyvalent Antivenom (VPAV) showed binding activity toward the venom protein antigens; however the immunorecognition of small proteins and PLA2-dominating fractions was low to moderate. Consistently, the antivenom neutralized the toxicity of the wild Pakistani Russell's viper venom at moderate efficacies. Our results suggest that it may be possible to enhance the Indian antivenom potency against the Pakistani viper venom by the inclusion of venoms from a wider geographical range including that from Pakistan into the immunogen formulation.

  4. Oh AMF, Tan CH, Ariaranee GC, Quraishi N, Tan NH
    J Proteomics, 2017 07 05;164:1-18.
    PMID: 28476572 DOI: 10.1016/j.jprot.2017.04.018
    The Indian krait (Bungarus caeruleus) is one of the "Big Four" venomous snakes widely distributed in South Asia. The present venomic study reveals that its venom (Sri Lankan origin) is predominated by phospholipases A2 (64.5% of total proteins), in which at least 4.6% are presynaptically-acting β-bungarotoxin A-chains. Three-finger toxins (19.0%) are the second most abundant, comprising 15.6% κ-neurotoxins, the potent postsynaptically-acting long neurotoxins. Comparative chromatography showed that venom samples from Sri Lanka, India and Pakistan did not exhibit significant variation. These venoms exhibited high immunoreactivity toward VINS Indian Polyvalent Antivenom (VPAV). The Pakistani krait venom, however, had a relatively lower degree of binding, consistent with its moderate neutralization by VPAV (potency=0.3mg venom neutralized per ml antivenom) while the Sri Lankan and Indian venoms were more effectively neutralized (potency of 0.44 mg/ml and 0.48 mg/ml, respectively). Importantly, VPAV was able to neutralize the Sri Lankan and Indian venoms to a comparable extent, supporting its use in Sri Lanka especially in the current situation where Sri Lanka-specific antivenom is unavailable against this species. The findings also indicate that the Pakistani B. caeruleus venom is immunologically less comparable and should be incorporated in the production of a pan-regional, polyspecific antivenom.

    BIOLOGICAL SIGNIFICANCE: The Indian krait or blue krait, Bungarus caeruleus, is a highly venomous snake that contributes to the snakebite envenoming problem in South Asia. This is a less aggressive snake species but its accidental bite can cause rapid and severe neurotoxicity, in which the patient may succumb to paralysis, respiratory failure and death within a short frame of time. The proteomic analysis of its venom (sourced from Sri Lanka) unveils its content that well correlates to its envenoming pathophysiology, driven primarily by the abundant presynaptic and postsynaptic neurotoxins (β-bungarotoxins and κ-neurotoxins, respectively). The absence of cytotoxins in the venom proteome also correlates with the lack of local envenoming sign (pain, swelling), and explains why the bite may be insidious until later stage when paralysis sets in. The muscarinic toxin-like proteins in the venom may be the cause of severe abdominal pain that precedes paralysis in many cases, and justifies the need of closely monitoring this symptom in suspected cases. Venom samples from Sri Lanka, India and Pakistan exhibited no remarkable variation in protein profiling and reacted immunologically toward the VINS Indian Polyvalent Antivenom, though to a varying extent. The antivenom is effective in neutralizing the Sri Lankan and Indian venoms, confirming its clinical use in the countries. The antivenom efficacy against the Pakistani venom, however, may be further optimized by incorporating the Pakistani venom in the antivenom production.

  5. Ong T, Suazo Di Paola A, Brookes C, Drummond A, Hendrick P, Leighton P, et al.
    BMJ Open, 2022 May 03;12(5):e050535.
    PMID: 35504639 DOI: 10.1136/bmjopen-2021-050535
    OBJECTIVE: To determine the feasibility of designing and conducting a definitive trial to evaluate the effectiveness of sacral fracture fixation compared with non-surgical management among older people admitted with a lateral compression pelvic fragility fracture (PFF).

    DESIGN: Single-site, parallel, two-arm randomised controlled feasibility trial.

    SETTING: A UK tertiary centre hospital.

    PARTICIPANTS: Patients aged ≥70 years who were ambulating pre-injury requiring hospital admission (within 28 days of injury) with a type 1 lateral compression PFF.

    INTERVENTIONS: The intervention group received sacral fracture fixation (cement augmentation±screw fixation) within 7 days of randomisation. Routine preoperative and postoperative care followed each surgical intervention. The control group received usual care consisting of analgesia, and regular input from the medical and therapy team.

    PRIMARY AND SECONDARY OUTCOME MEASURES: The feasibility outcomes were the number of eligible patients, willingness to be randomised, adherence to allocated treatment, retention, data on the completeness and variability of the proposed definitive trial outcome measures, and reported adverse events.

    RESULTS: 241 patients were screened. 13 (5.4%) were deemed eligible to participate. Among the eligible participants, nine (69.2%) were willing to participate. Five participants were randomised to the intervention group and four to the control group. The clinicians involved were willing to allow their patients to be randomised and adhere to the allocated treatment. One participant in the intervention group and two participants in the control group received their allocated treatment. All participants were followed up until 12 weeks post-randomisation, and had an additional safety follow-up assessment at 12 months. Overall, the proportion of completeness of outcome measures was at least 75%. No adverse events were directly related to the trial.

    CONCLUSIONS: There were significant challenges in recruiting sufficient participants which will need to be addressed prior to a definitive trial.

    TRIAL REGISTRATION NUMBER: ISRCTN16719542.

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