A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Therapeutic potential of human umbilical cord–derived mesenchymal stem cells transplantation in rats with optic nerve injury

Purpose: There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord–derived mesenchymal stem cell (hUC?MSC) transplantation in rats with optic nerve injury. Methods: Sprague–Dawley (SD) rats were divided into three groups: a no?treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC?MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology. Results: The fVEP showed shortened latency delay and increased amplitude in the hUC?MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC?MSC treated group compared with the BSS and control groups. Co?localized expression of STEM 121 and anti?S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions. Conclusion: Peribulbar transplantation of hUC?MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

Entomological study of chikungunya infections in the State of Kelantan, Malaysia.

Background & objectives: Chikungunya infection has become a public health threat in Malaysia since the 2008 nationwide outbreaks. Aedes albopictus Skuse has been identified as the chikungunya vector in Johor State during the outbreaks. In 2009, several outbreaks had been reported in the State of Kelantan. Entomological studies were conducted in Kelantan in four districts, namely Jeli, Tumpat, Pasir Mas and Tanah Merah to identify the vector responsible for the virus transmission. Methods: CHIKV cases records were obtained from State Health Department, Kelantan and localities involved were identified. Larva survey was conducted to collect the immature mosquito stages. Modified aspirators were used to collect the adult mosquitoes. All samples on dry ice were transferred to laboratory and the presence of the virus was detected using reverse transcriptase PCR. Results: A total of 1,245 mosquito larvae were collected during larval survey and 2,019 adult mosquitoes were collected using aspirator. From these collections, 640 mosquito pools were tested for the presence of CHIKV by RT-PCR but none found positive. Ae. albopictus was the most abundant mosquito collected, followed by Culex sp., Armigeres sp. and Anopheles sp. A total of 2, 814 artificial containers were inspected during the study. Interpretation & conclusions: Since none of the mosquito samples was found to be positive for chikungunya virus, the vector(s) of chikungunya virus in these localities could not be identified.

Cerebral schistosomiasis caused by Schistosoma mansoni: a case report with clinical analysis

Central nervous system involvement arising from schistosomiasis is uncommon. It may be produced most frequently by Schistosoma japonicum infection, but reports of S. mansoni presenting as an intracerebral mass lesion are particularly rare. The authors describe the case of a 35-year-old woman with a 3-month history of partial epileptic seizures and headaches. She immigrated to Egypt 4 years ago and had worked in Iraq for 2 years after the immigration. The patient's general physical and neurological examinations were unremarkable. Magnetic resonance [MR] imaging revealed an enhancing lesion with surrounding edema and mild mass effect in the left frontal lobe. A stereotactic brain biopsy demonstrated intraparenchymal granulomas surrounding S. mansoni eggs. S. mansoni was identified by stool examination. Prednisone [1 mg/kg per day for 1 week, with gradual withdrawal during the following 3 weeks] and praziquantel [2 doses at 20 mg/kg per day] therapy was initiated. The patient's symptoms resolved following medical treatment and the follow-up MR imaging yielded normal findings. This case is the rare imported case of cerebral schistosomiasis in China and the neuroschistosomiasis should be considered as the patient lived in a region in which this disease is endemic

Neuroretinitis with coexistent Bell's Palsy / 国际眼科杂志(Guoji Yanke Zazhi)

AlM:To report an unusual case of neuroretinits with coexistent Bell's Palsy.METHODS:A case report.RESULTS: A 16-year-old boy presented with right eye blurring of vision for one week. It was associated with high fever and facial asymmetry. The visual acuity of the right eye was 6/60 and the left eye was 6/6. Funduscopy of the right eye showed swollen and hyperemic optic disc with presence of macular star. There was also left lower motor neuron nerve palsy. Humphrey visual field perimetry showed small paracentral scotoma with enlargement of blind spot. Complete blood count showed neutrophilia with increased erythrocyte sedimentation rate (ESR). Serology for syphilis, toxoplasmosis, Lyme disease and cat-scratch disease was negative. Herpes simplex virus, Herpes zoster virus, and human immunodeficiency virus investigations were negative. Rickettsia was also negative. MRI of the brain and orbit were normal without demyelinating lesion. He was started with high dose intravenous methylprednisolone 250mg four times per day for three days. He was then discharged home with oral prednisolone 1mg/kg for another 11 days. During the follow-up,the visual acuity was improved to 6/6 after six months with slightly pale disc.The Bell's palsy was also improved without obvious facial asymmetry.CONCLUSION:It is important for clinician to examine other cranial nerces in optic neuritis. Although neuroretinitis with coexistent facial nerve in optic neuritis.Although neuroretinitis with coexistent facial nerve palsy is a rare conditon,thorough examinations and investigations should be made to exclude the inportant infetice causes.Optic neuritis with coexistent facial nerce palsy responds well to the high dose steroids.

Orbital abscess secondary to ethmoidal sinusitis in neonates / 国际眼科杂志(Guoji Yanke Zazhi)

A subperiosteal abscess is a form of orbital cellulitis characterized by a collection of fluid and pus confined by the periosteal lining of the orbit. In neonates, orbital abscesses are extremely rare. We present a case of a 26-day-old baby girl with severe orbital cellulitis in the right eye. A computed tomography (CT) scan of the orbits and paranasal sinuses revealed right orbital cellulitis with medial subperiosteal and retro-orbital abscess. The growth of Staphylococcus aureus was found in eye discharges. The patient was started on intravenous ceftriaxone and intravenous metronidazole. Urgent drainage of the abscess was performed via functional endoscopic sinus surgery (FESS). She recovered well after intravenous antibiotics and surgical drainage. Surgical drainage via endoscopic technique is the preferred treatment to prevent further complications.

Prevalence of refractive error in malay primary school children in suburban area of Kota Bharu, Kelantan, Malaysia

<p><b>INTRODUCTION</b>Refractive error remains one of the primary causes of visual impairment in children worldwide, and the prevalence of refractive error varies widely. The objective of this study was to determine the prevalence of refractive error and study the possible associated factors inducing refractive error among primary school children of Malay ethnicity in the suburban area of Kota Bharu, Kelantan, Malaysia.</p><p><b>MATERIALS AND METHODS</b>A school-based cross-sectional study was performed from January to July 2006 by random selection on Standard 1 to Standard 6 students of 10 primary schools in the Kota Bharu district. Visual acuity assessment was measured using logMAR ETDRS chart. Positive predictive value of uncorrected visual acuity equal or worse than 20/40, was used as a cut-off point for further evaluation by automated refraction and retinoscopic refraction.</p><p><b>RESULTS</b>A total of 840 students were enumerated but only 705 were examined. The prevalence of uncorrected visual impairment was seen in 54 (7.7%) children. The main cause of the uncorrected visual impairment was refractive error which contributed to 90.7% of the total, and with 7.0% prevalence for the studied population. Myopia is the most common type of refractive error among children aged 6 to 12 years with prevalence of 5.4%, followed by hyperopia at 1.0% and astigmatism at 0.6%. A significant positive correlation was noted between myopia development with increasing age (P <0.005), more hours spent on reading books (P <0.005) and background history of siblings with glasses (P <0.005) and whose parents are of higher educational level (P <0.005). Malays in suburban Kelantan (5.4%) have the lowest prevalence of myopia compared with Malays in the metropolitan cities of Kuala Lumpur (9.2%) and Singapore (22.1%).</p><p><b>CONCLUSION</b>The ethnicity-specific prevalence rate of myopia was the lowest among Malays in Kota Bharu, followed by Kuala Lumpur, and is the highest among Singaporean Malays. Better socio-economic factors could have contributed to higher myopia rates in the cities, since the genetic background of these ethnic Malays are similar.</p>

Bovine bone xenograft as orbital implants in rabbit eyes / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To assess the biocompatibility of bovine bone as orbital implants in rabbits.·METHODS: Bovine bone graft was used as an ocular implant in rabbits to determine whether it could be successfully used in the anophthalmic socket as an alternative to the expensive synthetic alloplastics. Evisceration of eyes with and without bovine bone orbital implantation was performed in the right eyes of 12 New Zealand white rabbits.Group Y (n =6) was eviscerated without implant, meanwhile Group X (n =6) was eviscerated with insertion of an orbital implant using bovine bone. Observation was carried out on day 1, day 7, day 14, day 28 and day 42. Serial clinical examination was carried out based on a few fixed criteria,which included rate of infection, implant migration, evidence of wound breakdown and any restriction of intraocular movements. The implanted eyes were then enucleated on day 42. The enucleated eyes were sent for histopathological evaluation to record the type of inflammatory reaction and rate of fibrovascular ingrowth.·RESULTS: Serial clinical examination showed presence of minimal infection in all eyes, both in Group X implanted) and Group Y (control) on first postoperative day, which responded well with antibiotics. Infection occurred in the implanted group after first postoperative day, but there was no evidence of orbital migration or extrusion of implant, wound breakdown, restriction of extraocular movement, severe infection or any physical abnormality. Histopathological examination revealed good fibrovascular ingrowth in the implanted group, with minimal rejecting reaction of rabbit eye towards bovine bone implant.·CONCLUSION: This study shows that bovine orbital implant has a good biocompatibility in rabbit eyes and its cost is acceptable.

An outbreak of echovirus 11 amongst neonates in a confinement home in Penang, Malaysia

Confinement homes are private institutions that provide full-time care for newborn babies and their respective postpartum mothers up to one month after delivery. An outbreak of fever and diarrhoea amongst newborns occurred in one such confinement home in Penang between the months of September to October 2004. An outbreak investigation was carried out including all babies, their respective mothers and workers in the home to determine the source of the outbreak and to institute control measures. Based on a working case definition of febrile illness with or without diarrhoea, 11 out of the 13 babies in the confinement home met the case definition. One hundred percent had symptoms of fever. 36.4% had symptoms of diarrhea and other respiratory conditions respectively. The attack rate of among babies in the confinement home was 90%. Echovirus 11 was isolated from 3 out of the 11 febrile cases. Echovirus 11 was isolated from the cerebrospinal fluid and stool of another baby at a private hospital that was epidemiologically linked to the first case. In conclusion, the outbreak of febrile illness amongst newborn babies in the affected confinement home was due to echovirus 11. The source was probably health-care associated with efficient transmission within the confinement home. The faecal-oral route was the most likely mode of transmission.

Functional outcome after major lower extremity amputation: a survey on lower extremity amputees

The post-operatve course of amputees is poorly documented. This cross-sectional survey was unertaken to determine functional outcomes of 213 patients who had undergone either a below-knee or above-knee amputation from 2000 to 2002 in a state-hospital setting. The study comprises a self-constructed questionnaire and interview conducted by phone. Of the 213 amputees, 41 out of 61 documented telephone numbers of the patients were useful for contact. Only 30 amputees were available for the study as the remaining 11 had passed away. Included in the questionnaire was the modified Barthel Index, a measurement to assess the amputees' ability to carry out activities of daily living (ADL). It contains ten questions pertaining to ADL with a total score of 20 points. Two-thirds of the respondents (67%) use their prosthesis for less than six hours per day. The Barthel Index of 30 patients ranged from 9-20 (mean 17.7). However, the mean Barthel Index in those with and without prosthesis was 18.4 and 15.2 respectively, but this difference was not significant. Half of the respondents were unable to maintain their pre-amputation jobs, while the remaining 50% were still able to work. Forty seven percent of amputees took less than a year to return to their activities, while 33% took between one to two years. Regarding the adequacy of preamputation information provided by the doctors, 73% amputees responded in the affirmative, while 27% felt otherwise. Amputees were still facing substantial disabilities following major amputation of the lower limb. Although 80% of respondents surveyed own prosthesis, the full use of prosthesis is suboptimal due to prosthetic-related problems. Most amputees had a good functional outcome based on the modified Barthel Index. Some amputees were unhappy as they felt that they were insufficiently informed regarding post-amputation expectation prior to the amputation. Despite good support from family, the community support for amputees is still lacking.

Adequacy of pain relief in closed manipulative reduction of fracture and dislocation

Adequate pain relief is a requisite for a successful closed manipulative reduction (CMR) of fractures and dislocations. This prospective study was undertaken to assess the mode and adequacy of pain relief given to patients undergoing such procedures at Seremban Hospital from the 1st April to the 31st May 2001. All patients with fractures and dislocations scheduled to undergo CMR were included in this study. The type of sedative agents and analgesia administered were recorded. Demographic data and the type of fracture or dislocation of the selected patients were documented. A visual analogue scale (VAS) for pain perception was given to both to the patients and the medical personnel who performed the procedure. All data were collected manually before entered into computerized database for analysis. Of 72 patients included in this study, 47% were Malay, 26% Indian, 21% Chinese and 6% others. There was male predominance and the patients' age ranged between 9 to 79 years (average 27.4 years). Upper limb injuries (79%) were mainly fractures of the radius and ulna (29%) and isolated fracture radius (21%). For the lower limb injuries (21%), combined tibia and fibula fractures constituted 10% of the total cases followed by isolated tibia fractures (10%) and hip dislocation (1%). The most common pain relieving agents given during the CMR were intravenous pethidine alone (43%) followed by combination of intravenous pethidine and valium (36%), intramuscular pethidine (17%) and intramuscular tramal (4%). The Visual Analogue Score (VAS) for pain perception revealed that 61% of the patients had moderate pain while 21% had severe pain during the course of the procedures. Suboptimal pain relief administered during CMR should prompt positive actions to ensure that the patient is not subjected to undue pain just for the sake of an acceptable fracture reduction.

The epidemiology of shoulder dislocation in a state-hospital: a review of 106 cases

This retrospective study was conducted in a state hospital set-up and aimed at identifying the magnitude of shoulder dislocations and their demographic data, characteristics of the injury, mechanism and predisposing factors, and the instituted treatment. Patients with radiographic evidence of shoulder dislocation admitted to the hospital from January 1999 to December 2002 were included. Data were recorded from the case notes. There were 105 shoulder dislocations with male predomination in 77% cases and age ranged between 11 and 90 years (average 30.9 years). The right shoulder was affected in 68% of the cases. The contributing events were fall in 37% of cases, road traffic accident 23%, sports 17% and pathological conditions 13%. Anterior dislocation occurred in 96.2% of the cases. Posterior and inferior dislocations encountered in two patients for each type. Twelve dislocations were associated fracture of the greater tuberosity, two each with humeral neck fracture and cerebral injuries. First time dislocation occurred in 73.6% of the cases. The recurrences ranged between 2 to 6 times (average 3.4 times). Closed manipulative reduction and strapping was the definitive treatment in 92.4% of the cases and the remaining needed surgical reconstruction. Four patients had open reduction and internal fixation of the associated fractures while another four had arthroscopic Bankart's repair. In conclusion, shoulder dislocation represents the most common shoulder problems. It afflicted young adults of reproductive age (21-40 years) and participation in sports was a risk factor in men. Women over 40 years and fall were at risk to develop shoulder dislocation.

Sports-related shoulder dislocations: a state-hospital experience

This retrospective study was conducted in a state hospital set-up and aimed at identifying the incidence of sports-related shoulder dislocations and their characteristics and the sports events involved. All patients with shoulder dislocation related to sporting activities admitted to the hospital from January 1999 to December 2002 were included in the study. There were 18 sports-related shoulder dislocations out of 106 all shoulder dislocations admitted during this 4-year period. The average age of the patients was 25.4 years. All but two were male. All were anterior dislocations. Recurrent dislocation constitutes 78% of the cases with an average of 3 times re-dislocation. Rugby and badminton were the major contributors to the injuries followed by volleyball, soccer and swimming. Conservative treatment was successfully instituted for 88% of the patients and 12% opted for surgical intervention.

Unicameral bone cyst of the calcaneum

The calcaneus is not a common site for a unicameral solitary bone cyst. Little is known about the etiology and natural history of these lesions. The author reports an adult man with a solitary bone cyst of the os calcis which was confirmed radiologically and histologically and successfully treated with curretage and bone grafting.