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Podophyllotoxin is a nonalkaloid toxin aryltetralin lactone lignan, occurring naturally and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives have been shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic and antiviral properties. Podophyllotoxin serves as a potential anticancer agent and also the precursor for the chemical synthesis of some clinically important anticancer agents. The chemical modification and pharmacological investigation of podophyllotoxin derivatives have become a concern nowadays. Research interest has been stimulated towards the innovation of podophyllotoxin derivatives as the semi-synthetic anticancer agents, especially etoposide and teniposide. Podophyllotoxin and its derivatives are available in several formulations and also found to be effective in combination therapy. This review article aims to provide an overview of the role of podophyllotoxin, its mechanism of action, pharmacological activities, pharmacokinetics, available formulations, and its effects in combination therapy. This article also reviews the biosynthesis, structure and modifications of podophyllotoxin and its derivatives as an anticancer agent.

OBJECTIVE Frailty is associated with morbidity and mortality in older injured patients. However, for older blunt-trauma patients, increased frailty may not manifest in longer length of stay at index admission. We hypothesized that owing to time spent in hospital from readmissions, frailty would be associated with less total time at home in the 1-year postinjury period. DESIGN Prospective, nationwide, multicenter cohort study. SETTING AND PARTICIPANTS All Singaporean residents aged ≥55 years admitted for blunt trauma with an Injury Severity Score (ISS) or New Injury Severity Score (NISS) ≥10 from March 2016 to July 2018. METHODS Frailty (by modified Fried criteria) was assessed at index admission, based on questions on preinjury weight loss, slowness, exhaustion, physical activity, and grip strength at the time of recruitment. Low time at home was defined as >14 hospitalized days within 1 year postinjury. The contribution of planned and unplanned readmission to time at home postinjury was explored. Functional trajectory (by Barthel Index) over 1 year was compared by frailty. RESULTS Of the 218 patients recruited, 125 (57.3%) were male, median age was 72 years, and 48 (22.0%) were frail. On univariate analysis, frailty [relative to nonfrail: odds ratio (OR) 3.45, 95% confidence interval (CI) 1.33-8.97, P = .01] was associated with low time at home. On multivariable analysis, after inclusion of age, gender, ISS, intensive care unit admission, and surgery at index admission, frailty (OR 5.21, 95% CI 1.77-15.34, P < .01) remained significantly associated with low time at home in the 1-year postinjury period. Unplanned readmissions were the main reason for frail participants having low time at home. Frail participants had poorer function in the 1-year postinjury period. CONCLUSIONS AND IMPLICATIONS In the year following blunt trauma, frail older patients experience lower time at home compared to patients who were not frail at baseline. Screening for frailty should be considered in all older blunt-trauma patients, with a view to being prioritized for postdischarge support.

Myocardial dysfunction is a known complication in patients who experience severe stressful events, such as traumatic brain injuries (TBI). One common manifestation is Takotsubo Cardiomyopathy (TC) which can appear concomitantly in patients with haemorrhagic brain injuries. There is often a management dilemma when two conditions with conflicting treatment regimens arise in the same individual. Previous systematic review had highlighted the importance of accurate diagnosis but there is no algorithm to aid decision-making in an emergency trauma setting. A systematic review was performed with the aim of establishing a new algorithm to aid in the diagnosis and management of TC patients with concurrent TBI.We performed a comprehensive search of Pubmed, google scholar, Embase and Cochrane databases using keywords 'traumatic brain injury' and 'head injury' associated with keywords of 'Takotsubo cardiomyopathy,' 'Tako-tsubo cardiomyopathy,' 'stress cardiomyopathy,' 'stunned myocardium,' 'transient-left-ventricular ballooning syndrome,' 'apical ballooning syndrome,' 'myocardial dysfunction' or 'heart failure'. Non traumatic brain injury, blunt cardiac injury or cardiac events from chest trauma were excluded. The search was done between 1st to 4th October 2020 and only articles published after the year 2000 in English were included. Articles were then analysed in-depth. No articles were excluded after analysis to remove reporting bias.A total of 11 case reports and 7 cohort studies were analysed, giving a total number of 382 patients, with 36% of the patients analysed presenting with subdural haematoma, 27% with subarachnoid haemorrhage and 5% with extradural haematoma. Of the patients who underwent surgical interventions for traumatic brain injuries, 75% survived. 9% of patients in total were reported to have an EF of less than 55% whereas 51% had an EF of equal to or more than 55%. TTE details were not reported in a total of 35% of patients. All case reports which had followed up on their patient's cardiac status with repeated echocardiography had demonstrated a resolution of cardiac function independent of cardiac intervention.Our analysis was limited by the fact that not all papers analysed had reported the parameters we required. However, based on our review, we conclude that most patients with TC demonstrate a resolution of cardiac function independent of cardiac interventions from as fast as a few hours to as long as 6-12 weeks. Therefore, despite high cardiac risks, if neurosurgical intervention is needed, it should be offered to improve the chance of survival as transient cardiomyopathy can be supported with inotropes. We have developed a new algorithm for management of cases of concurrent TBI and TC.

Purpose. To report injury patterns and management of musculoskeletal injuries after an earthquake. Methods. 94 male and 161 female patients aged 17 to 90 (mean, 53) years underwent surgery for musculoskeletal injuries. Their injury patterns, anaesthesia administered, surgeries undertaken, and development of postoperative complications were reviewed. Results. Of the 255 patients, 155 sustained superficial lacerations with minor soft-tissue contusion, whereas 100 sustained injuries that necessitated surgery under anaesthesia. The injuries involved the tibia/ankle (n=90), the hand (n=48), the pelvis/femur (n=41), the radius/ulnar (n=36), the foot (n=20), the humerus (n=10), and the spine (n=10). 30 (12%) of the patients had multiple injuries. The most common procedure performed was debridement (n=58), followed by open reduction and internal fixation with plates and screws for closed fractures (n=20), Kirschner wiring (n=11), external fixation (n=8), and general surgery and others (n=6). Repeated debridements were performed for 19 open fractures; 10 involved the distal tibia. 63 procedures were carried out under anaesthesia or sedation. General anaesthesia involved 2 patients; one had a right hemi-colectomy for an ischaemic bowel and another had an appendicectomy. Regional anaesthesia included sub-arachnoid block for lower-limb surgeries (n=21), axillary brachial plexus block for upper-limb surgeries (n=11), and femoral and sciatic nerve blocks for a lower-limb surgery (n=1). The remaining 28 procedures involved conscious sedation. The mean number of debridements for open fractures was 2.8 (range, 2–5). The mean follow-up duration was 10.4 (range, 7–14) days. Only one patient developed a postoperative wound infection. Conclusion. Our team was effective in managing orthopaedic injuries after an earthquake. The postoperative complication rate was low. Regional and spinal anaesthesia are relatively safe alternatives to general anaesthesia when carried out under such austere circumstances. The success of the mission depended on collaboration with the local health care workers and external agencies.

Few studies have prospectively analysed the delivery of care in trauma patients. This study undertook a prospective analysis of performance and consistency of care at a Level 1 trauma centre. A 3-month prospective study was undertaken of all admitted trauma patients at Liverpool Hospital. Data were collected on patient demographics, mechanism of injury, injury severity score (ISS), length of hospital stay, patient outcome and cause of death. Delivery of care was evaluated using 30 performance indicators and assessment of errors. Two hundred and thirty-six consecutive major trauma patients were studied. 73.3% were male, mean age 39 years. The main mechanism of injury was road trauma in 46.2%. Mean ISS was 12 and 64 patients had an ISS > or = 16. Error-free care was delivered in 145/236 (61.4%). There were 145 errors in 91 patients (38.6%). Errors in judgement and delays in diagnosis accounted for 56/145 (38.6%) and 48/145 (33.1%), respectively. Errors occurred most commonly in the Emergency Department (ED) (48.3%), and trainees from all specialties were responsible for 67.5% of errors. There were 25 near misses detected. Three patients developed major sequelae or complications from errors. One of 13 deaths was deemed potentially preventable. This study has shown that while 61.4% of admitted trauma patients receive optimal care, errors are frequent, resulting in a spectrum of outcomes from near misses to death. The majority of errors result from the activity of unsupervised trainees and relate to errors in judgement and delays in diagnosis. Clearly, there is room for improvement of the delivery of trauma care.

Objective The detection of flat colorectal lesions with possible malignant potential has been described by Japanese endoscopists. This study looks at the detection of flat lesions using standard colonoscopic techniques and examines the clinical significance of these lesions. Methods The records of patients who underwent complete colonoscopy by a single colorectal surgeon in an outpatient setting over a 4-year period were reviewed. The site and number of flat lesions and their histology were noted. Patients with incomplete intubation of the colon were excluded. Results A total of 491 patients underwent 593 colonoscopic examinations. There were 236 flat lesions identified in 91 patients: 24% (56/236) were adenomas showing mild or moderate dysplasia, and 63% (148/236) were hyperplastic. Conclusions Flat colorectal lesions are common and can be detected without the aid of dye spray and magnification. One-quarter of these lesions are adenomatous and we recommend routine hot biopsy or polypectomy of these lesions.