Autologous chondrocyte implantation (ACI) is a significant technique that has gained widespread use for the treatment of focal articular cartilage damage. Since its inception in 2004, the Tissue Engineering Group (TEG) of the Faculty of Medicine, University Malaya has been dedicated to carrying out extensive research on this cell-based therapy. The objective of this report, comprising one clinical case report, six animal studies and one laboratory study, is to summarise and discuss TEG’s key findings. On the whole, we observed that the ACI technique was effective in regenerating hyaline-like cartilage in treated defects. Autologous chondrocytes and mesenchymal stem cells (MSC) were found to produce comparable tissue repair irrespective of the state of MSC differentiation, and the use of alginate-based scaffolding and oral pharmacotherapy (Glucosamine and Chondroitin Sulphate) was shown to enhance ACI-led tissue repair. ACI is suggested to be an efficient therapeutic option for the treatment of articular cartilage defects of the knee.
Cartilage, Articular

Cancer recurrence and severe side effects of currently being used chemotherapeutic agents reduce their clinical efficacy. Thus, there is a constant need to develop alternative anticancer drugs. Sustainable supply is an important challenge facing marine-based drug discovery. Primmorph, a 3D cell culture system, could provide a sustainable source to produce metabolites for anticancer drugs from marine sponges. In the present work, the anticancer activity of primmorph extracts and mesohyls of Negombata magnifica, Hemimycle arabica, Crella spinulata, and Stylissa carteri sponges was evaluated. Anti-proliferative activity was studied in terms of cytotoxicity, colony formation, cell cycle, and apoptosis. Migration was assessed by migration assay and matrix metalloproteinase activity. The expression of proliferation and migration-related genes was analyzed using real time PCR. Migration and proliferation activities of HepG2 cells were inhibited by treatment with primmorph extracts and mesohyls of N. magnifica, H. arabica, and C. spinulata. The mesohyl of S. carteri did not show any anticancer activity although the primmorph extract led to cell cycle arrest. Among the selected sponge species, the prim-morph extract of C. spinulata was the most promising anticancer agent regarding antiproliferative and antimigratory activities. In addition, primmorph extracts have the advantage of working under well-defined and controlled conditions, which allows the easy application as a bioreactor.

Synthetic cathinones are new psychoactive substances that represent a health risk worldwide. For most of the 130 reported compounds, information about toxicology and/or metabolism is not available, which hampers their detection (and subsequent medical treatment) in intoxication cases. The principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stab-lishing the most appropriate biomarkers for these substances. Human metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers;however, this type of samples is limited and difficult to access. In this work, the metabolic behaviour of three synthetic cathinones (4-CEC, 4-CPrC and 5-PPDi) and one amphetamine (3-FEA) has been evalu-ated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass spectrometry. This in vitro approach has previously shown its feasibility for obtaining excretory human metabolites. 4-CEC and 3-FEA were not metabolised, and for 4-CPrC only two minor metabolites were obtained. On the contrary, for the recently reported 5-PPDi, twelve phase I metabolites were elucidated. Up to our knowledge, this is the first metabolic study of an indanyl-cathinone. Data reported in this paper will allow the detection of these synthetic stimulants in intoxi-cation cases, and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones.

Introduction: Proton pump inhibitors (PPI) have been used as stress ulcer prophylaxis (SUP) in intensive care unit (ICU) patients due to their high risk for stress-related upper gastrointestinal (GI) bleeding. With its dramatic increase in prescription, studies have noted its misuse and associated complications. This study aimed to determine the appropriateness of the use of PPIs in adult patients in the ICU of Medical Center Manila (ManilaMed). Methods: This eight-month study conducted a retrospective chart review, and analyzed through descriptive statistics using Stata 13. Out of 292 patients, 188 satisfied the inclusion and exclusion criteria. The indication of use of PPI was based on the American Society of Health-System Pharmacists (ASHP) Therapeutic Guidelines on SUP. Results: The patients were mostly male, median age of 62 years, stay in the ICU of five days, overall hospital stay of 13 days, and 75% were admitted from the emergency room. About 58% of PPIs were prescribed in the intravenous route for an average of 10 days, 38% of which is prescribed by cardiology consultants. Of the 73% of patients prescribed PPIs, most were septic and intubated for >48 hours, as well as being older and with longer overall hospital stay. Only 53.7% were prescribed appropriately; adverse outcomes included pneumonia, GI bleeding, anemia, renal failure, combined complications and overall mortality. Discussion: The 46% inappropriate use of PPIs may indicate its routine use was common. The adverse outcomes, despite appropriate use, cannot be concluded as having causative effect owing to the nature of the study and given the possibility that these patients may have been sicker on admission hence prescribed the PPI. Conclusion Results indicated that PPI prescription in the ICU were mostly guidelines compliant. This paper recommends the development of ManilaMed’s own strategies to minimize its inappropriate use, in turn allowing proper allocation of funds and maximizing medical treatment.
Proton Pump Inhibitors

Background: Infective Endocarditis (IE) is an infection of the endocardial surface of the heart. It remains a life threatening infection among extremes of ages and erroneous or late diagnosis may lead to serious consequences. Objective: To determine the clinical profile and treatment outcomes of pediatric patients with IE admitted in a pediatric medical center. Methods: This is a retrospective descriptive study on pediatric patients (0-18 years old) diagnosed with IE from January 2005 to June 2016. Patients’ medical records that satisfied the criteria for IE based on Modified Duke Criteria were included in the study. Results: A total of 37 charts were reviewed with male to female ratio of 1:1. Most common chief complaint and physical finding were difficulty of breathing and tachycardia,respectively.Cardiac murmur was appreciated upon diagnosis except in one patient. 70% had ventricular septal defect and 24% had rheumatic heart disease. Most common associated non-cardiac condition was the presence of dental caries, while only 11% had history of previous cardiac surgeries. 2-Dimensional Echocardiography (2D-Echo) showed vegetation in 97.2% and 49% had positive growth in blood culture. Most common isolate was Streptococci. Empiric therapy included penicillin G (84%) with gentamicin (76%). Complications noted were brain infarct,pericarditis and pulmonary embolism. Majority were managed medically, 7 patients (19%) had vegetectomy and 9(24%)died during hospitalization. Conclusion IE is a common complication of congenital heart disease.High index of suspicion is warranted for the early management and prevention of morbidity and mortality.
Endocarditis ; Heart Defects, Congenital

Objective To investigate alterations in the microtubule-associated protein 2 (MAP-2) of neurons in Wistar rats and the effect of nimodipine (Nim), D-2-amino-5-phosphonovaleric acid (D-AP-5) and mild hypothermia on neuronal MAP-2 following fluid percussion injury (FPI). Methods Alterations of MAP-2 in Wistar rat neurons following FPI were measured by a confocal laser scanning microscope using MAP-2 immunofluorescence staining as a MAP-2 indicator. Results MAP-2 immunofluorescence staining was limited to the cell bodies and dendritic compartments of neurons and more intense in dendrites than in cell bodies. The loss of MAP-2 was marked at 3 h post trauma ( P ＜ 0.01 ), and reached a maximum at 48 h post-trauma. Afterwards, fluorescence recovered partly at 72 h post-trauma. The application of Nim markedly reduced the loss of MAP-2 immunoreectivity within 1 h post-trauma ( P ＜ 0.01 ), and the application of D-AP-5 markedly reduced the loss of MAP-2 immunoreactivity within 10 h post-injury ( P ＜ 0.01 ). The application of mild hypothermia decreased the loss of MAP-2 immunoreactivity within 1 h post-injury (P＜ 0.05). Conclusions The partial recovery of fluorescence at 72 h post-trauma indicate that the partial structure of the neuronal microtubules can be repaired by itself. Nim, D-AP-5 and mild hypothermia reduce the degradation of MAP-2 by different mechanisms. The treatment of neuronal cytoskeleton degradation following FPI must employ multiple therapeutic approaches.

Purpose: The purpose of this study was to compare the concurrent validity and test-retest reliability of ‘KPIMT Torticollis Protractor’, a smart phone and I-pad application for convenient range of motion measurement, and ‘Image J’, an analysis software with high reliability and validity, according to head tilt and active cervical rotation angle. This was done to determine the clinical utility of ‘KPIMT Torticollis Protractor’. Methods: Head tilt and active cervical spine rotation angles of 40 children with congenital muscular torticollis were measured using Image J and KPIMT Torticollis Protractor, respectively. The level of concurrent validity and inter-rater and intra-rater reliability between the two measurement methods were analyzed. Results: For forty participants, the concurrent validity between Image J and KPIMT Torticollis Protractor showed very high validity with ICC of ICC 0.977 (0.995-0.999), 0.994 (0.994-0.998), CVME% 0.71-0.72%, SEM% 0.31-0.34%, MDC% 0.86-0.94%. The test-retest intra-rater reliability showed very high reliability ICC 0.911 (0.911-0.966), CVME% 0.71%, SEM% 0.34-0.36%, MDC% 0.81-0.94%. The test-retest inter-rater showed very high reliability ICC 0.936 (0.933-0.957), CVME% 0.70%, SEM% 0.34-0.35%, MDC% 0.81-0.83%. Conclusion The KPIMT Torticollis Protractor, a smart phone and IPD application, is a highly reliable and valid device for angle measurement in children with congenital myotonia and can be easily used in clinical practice.

Context: Endometrial cancer is the third most common malignancy of the female genital tract in the Philippines, following cervical and ovarian cancer. Ultrasound as the first line in imaging has a major role in preoperative treatment and planning. Aims: To compare the diagnostic accuracy of subjective versus objective ultrasound measurement techniques in detecting cervical stromal invasion (CSI) and deep myometrial invasion (MI). Materials and Methods: Fifty‑seven patients were enrolled in this cross‑sectional study. Deep MI and CSI were evaluated both subjectively and objectively by measuring tumor‑free distance (TFD), distance from the outer cervical os to lowest edge of the tumor border (Dist‑OCO), and distance from the internal cervical os to caudal tumor border (Dist‑ICO). Histopathological result used as the gold standard. Results: Subjective assessment for deep (MI) had 79.3% sensitivity, 82.1% specificity, 82.1% positive predictive value (PPV), 82.1% negative predictive value (NPV), and 80.7%. Subjective assessment for CSI had a sensitivity, specificity, PPV, NPV, and overall accuracy of 80%, 90.4%, 44.4%, 97.9%, and 89.5%. Objective measurement (TFD ≤0.8 cm) to detect deep MI had 86.2% sensitivity, 57.1% specificity, 67.4% PPV, 80% NPV, and 71.9% overall accuracy. Adjusting TFD cutoff to 0.65 increased to 71.4% specificity, making it comparable with subjective assessment. Dist‑OCO (≤2.1 cm) yielded 100% sensitivity, 86.3% specificity, 30% PPV, 100% NPV, and 87% overall accuracy. Dist‑ICO was first used in this study, hence no cutoff yet. By using receiver operating characteristics, cutoff was 0.45 cm, which yielded a 60% sensitivity and 92% specificity (area under the curve 0.731, P = 0.09). Conclusions Subjective assessment of CSI and deep MI performs better than objective measurement techniques. TFD and Dist‑OCO as the objective measurements showed clinically comparable accuracy to subjective assessment by an expert. Dist‑ICO needs to be validated to a larger population to determine its clinical value in predicting CSI.
Endometrial Neoplasms

Respiratory symptoms are the most common manifestation of COVID-19 across all age groups and it is most often associated with radiographical findings consistent with pneumonia.2 A recent systematic review estimated that 16% of children with SARS-CoV-2 infection are asymptomatic,3 or others may present with seizures, gastrointestinal bleeding or jaundice. This reports a 2-year old boy with no known co-morbidity who had a 2-week history of abdominal pain and jaundice then had a rapidly progressive course of neurological deterioration and eventual demise. He had markedly elevated liver enzymes and deranged bleeding parameters with elevated ammonia and ferritin levels. Hepatitis B and hepatitis A titers were non-reactive. He was managed as a case of hepatic encephalopathy secondary to cholestatic jaundice. His chest x-ray was normal but his SARS-CoV-2 RT PCR result was positive with a low cycle threshold. Locally, this is the first reported case of SARS-CoV-2 RT-PCR positive pediatric patient presenting as fulminant hepatic failure with no associated respiratory manifestations. Clinicians should be mindful that such presentation, however uncommon, is possible and a high index of suspicion should be maintained.
COVID-19 ; SARS-CoV-2 ; Liver Failure ; Massive Hepatic Necrosis