Salvage neck surgery in recurrent nodal NPC: Do all patients require a comprehensive neck dissection in the modern MRI era?

OBJECTIVE: The standard treatment for regional failure in nasopharyngeal carcinoma (NPC) is the radical neck dissection (RND). Our study sought to determine if magnetic resonance imaging (MRI) may accurately predict nodal involvement to allow selected levels of neck dissection to be preserved. STUDY DESIGN AND SETTING: We analysed retrospectively all NPC patients in our centre undergoing neck dissections as salvage therapy for nodal recurrence. Nodal involvement based on the preoperative MRI was assessed and compared with postoperative histopathology. METHODS: This is a retrospective study conducted on patients in our centre with recurrent NPC from February 2002 to February 2017. Patients were identified from the database of the otolaryngology oncology division at our institution. Of these, 28 patients met all our inclusion and exclusion criteria. We calculated sensitivity and specificity as well as average number of nodes per patient. RESULTS: In our study, we calculated the false negative and false positive rates of preoperative MRI neck by levels. Overall sensitivity of MRI picking up disease by level was 76% and specificity was 86%. CONCLUSION: Based on our study, we will be missing a total of 10 (7.1%) diseased neck levels in eight (28.5%) patients. MRI alone, therefore, does not provide enough information to allow safe selective preservation of neck levels in surgical salvage of neck recurrences in NPC.

Olfactory taste disorder as a presenting symptom of COVID-19: a large single-center Singapore study.

PURPOSE: To investigate the prevalence and epidemiological risk factors of olfactory and/or taste disorder (OTD), in particular isolated OTD, in patients with laboratory-confirmed COVID-19 infection. METHODS: We conducted a retrospective and cross-sectional study. Patients with laboratory-confirmed COVID-19 infection were recruited from the National Centre for Infectious Diseases (NCID) Singapore between 24 March 2020 and 16 April 2020. The electronic health records of these patients were accessed, and demographic data and symptoms reported (respiratory, self-reported OTD and other symptoms such as headache, myalgia and lethargy) were collected. RESULTS: A total of 1065 patients with laboratory-confirmed COVID-19 were recruited. Overall, the prevalence of OTD was 12.6%. Twelve patients (1.1%) had isolated OTD. The top three symptoms associated with OTD were cough, fever and sore throat. The symptoms of runny nose and blocked nose were experienced by only 29.8 and 19.3% of patients, respectively. Multivariate analysis demonstrated that the female gender, presence of blocked nose and absence of fever were significantly associated with OTD (adjusted relative risks 1.77, 3.31, 0.42, respectively). All these factors were statistically significant. CONCLUSION: Patients with COVID-19 infection can present with OTD, either in isolation or in combination with other general symptoms. Certain demographic profile, such as being female, and symptomatology such as the presence of blocked nose and absence of fever, were more likely to have OTD when infected by COVID-19. Further studies to elucidate the pathophysiology of OTD in these patients will be beneficial.

COVID-19, circuit breaker and safe reopening - perspective from an ENT practice at a tertiary hospital in Singapore.

COVID-19 has affected every walk of life, including the healthcare sector. In this article, we discuss how an Otolaryngology department in a tertiary hospital in Singapore had to adapt to the pandemic in areas of outpatient care, elective surgeries, personal protection, residency training, education and research. Documenting our experience has helped us to understand the areas of work which can be affected in a pandemic and the factors that have helped to mitigate disruption. This will prove useful in our approach to subsequent pandemics.

Seroprevalence of antibodies to Rickettsia typhi in the Waikato region of New Zealand.

The first reported New Zealand-acquired case of murine typhus occurred near Auckland in 1989. Since then, 72 locally acquired cases have been recorded from northern New Zealand. By 2008, on the basis of the timing and distribution of cases, it appeared that murine typhus was escalating and spreading southwards. To explore the presence of Rickettsia typhi in the Waikato region, we conducted a seroprevalence study, using indirect immunofluorescence, Western blot, and cross-adsorption assays of blood donor samples. Of 950 human sera from Waikato, 12 (1·3%) had R. typhi antibodies. The seroprevalence for R. typhi was slightly higher in northern Waikato (1·4%) compared to the south (1·2%; no significant difference, χ 2 P = 0·768 at P < 0·05). Our results extend the reported southern range of R. typhi by 140 km and indicate it is endemic in Waikato. Evidence of past Rickettsia felis infections was also detected in six sera. Globally, R. felis is an emerging disease of concern and this pathogen should also be considered when locally acquired rickettsiosis is suspected. If public health interventions are to be implemented to reduce the risk of rickettsioses as a significant public health problem, improvements in rickettsial diagnostics and surveillance will be necessary.

Clinical features and management of haemophilic pseudotumours: a single US centre experience over a 30-year period.

Given the rarity of haemophilic pseudotumours, consensus on management is lacking. We describe the clinical features and management of haemophilic pseudotumours by retrospectively reviewing the medical records of haemophilia patients with a diagnosis of pseudotumour seen at our Hemophilia Center from 1981 to 2011. We recorded the following data: type and severity of haemophilia, documented aetiological antecedent, localization of the pseudotumour, presenting symptoms, management and outcome. We identified 12 pseudotumours in 11 patients over a 30-year period. Six patients had known inhibitors or a history of inhibitor. An aetiological antecedent leading to the development of pseudotumour was reported in nine cases. Localization of the pseudotumour was confined to soft tissue (n = 3) and bone (n = 8). Six of the 12 pseudotumours (50%) were not diagnosed at the time of initial presentation, with a delay ranging from 6 weeks to 6 years. In eight cases, surgical intervention (surgical drainage, n = 2; excision, n = 4; limb amputation, n = 2) was the initial treatment choice, with complete resolution in six cases. Conservative management with close monitoring occurred in three cases, with one case subsequently requiring surgical resection. We conclude that haemophilic pseudotumours still occur sporadically, and the diagnosis is frequently delayed. Surgical intervention is generally a safe and effective treatment, although conservative management may be appropriate in selected cases.

Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population.

INTRODUCTION: Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency. OBJECTIVE: To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength. DESIGN AND METHODS: Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants. RESULTS: 53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p = <0.001). Chinese had the lowest level of VDBP (169.6ug/ml) followed by Malay (188.8 ug/ml) and Indian having the highest (220.1 ug/ml). Calculated bioavailable and free 25(OH)D levels were significantly higher in Chinese, followed by Malays and Indians, which also correlated with better grip strength measures amongst the Chinese. CONCLUSION: The Malays and Indians had overall lower free, bioavailable and total 25(OH)D compared with ethnic Chinese. Chinese ethnic group also had the lowest VDBP and better overall grip strength.

Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity.

Extracts of bakers' yeast (Saccharomyces cerevisiae) contain protein-tyrosine kinase activity that can be detected with a synthetic Glu-Tyr copolymer as substrate (G. Schieven, J. Thorner, and G.S. Martin, Science 231:390-393, 1986). By using this assay in conjunction with ion-exchange and affinity chromatography, a soluble tyrosine kinase activity was purified over 8,000-fold from yeast extracts. The purified activity did not utilize typical substrates for mammalian protein-tyrosine kinases (enolase, casein, and histones). The level of tyrosine kinase activity at all steps of each preparation correlated with the content of a 40-kDa protein (p40). Upon incubation of the most highly purified fractions with Mn-ATP or Mg-ATP, p40 was the only protein phosphorylated on tyrosine. Immunoblotting of purified p40 or total yeast extracts with antiphosphotyrosine antibodies and phosphoamino acid analysis of 32P-labeled yeast proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the 40-kDa protein is normally phosphorylated at tyrosine in vivo. 32P-labeled p40 immunoprecipitated from extracts of metabolically labeled cells by affinity-purified anti-p40 antibodies contained both phosphoserine and phosphotyrosine. The gene encoding p40 (YPK1) was cloned from a yeast genomic library by using oligonucleotide probes designed on the basis of the sequence of purified peptides. As deduced from the nucleotide sequence of YPK1, p40 is homologous to known protein kinases, with features that resemble known protein-serine kinases more than known protein-tyrosine kinases. Thus, p40 is a protein kinase which is phosphorylated in vivo and in vitro at both tyrosine and serine residues; it may be a novel type of autophosphorylating tyrosine kinase, a bifunctional (serine/tyrosine-specific) protein kinase, or a serine kinase that is a substrate for an associated tyrosine kinase.

Thrombin generation and cell-dependent hypercoagulability in sickle cell disease.

Essentials Sickle cell disease is increasingly being recognized as a chronic hypercoagulable state. Thrombin generation is elevated in the whole blood, but not the plasma of sickle cell patients. Whole blood thrombin generation inversely correlates to erythrocyte phosphatidylserine exposure. Acquired protein S deficiency is likely explained by binding of protein S to sickle red cells. Click to hear Dr Hillery discuss coagulation and vascular pathologies in mouse models of sickle cell disease. SUMMARY: Introduction Sickle cell disease (SCD) is a hypercoagulable state with chronic activation of coagulation and an increased incidence of thromboembolic events. However, although plasma pre-thrombotic markers such as thrombin-anithrombin complexes and D-dimer are elevated, there is no consensus on whether global assays of thrombin generation in plasma are abnormal in patients with SCD. Based on our recent observation that normal red blood cells (RBCs) contribute to thrombin generation in whole blood, we hypothesized that the cellular components in blood (notably phosphatidylserine-expressing erythrocytes) contribute to enhanced thrombin generation in SCD. Methods Whole blood and plasma thrombin generation assays were performed on blood samples from 25 SCD patients in a non-crisis 'steady state' and 25 healthy race-matched controls. Results Whole blood thrombin generation was significantly elevated in SCD, whereas plasma thrombin generation was paradoxically reduced compared with controls. Surprisingly, whole blood and plasma thrombin generation were both negatively correlated with phosphatidylserine exposure on RBCs. Plasma thrombin generation in the presence of exogenous activated protein C or soluble thrombomodulin revealed deficiencies in the protein C/S anticoagulant pathway in SCD. These global changes were associated with significantly lower plasma protein S activity in SCD that correlated inversely with RBC phosphatidylserine exposure. Conclusion Increased RBC phosphatidylserine exposure in SCD is associated with acquired protein S deficiency. In addition, these data suggest a cellular contribution to thrombin generation in SCD (other than RBC phosphatidylserine exposure) that explains the elevated thrombin generation in whole blood.

PM10 mass concentration and oxidative capacity of moxa smoke.

BACKGROUND: The burning of moxa floss in moxibustion releases moxa smoke containing a substantial amount of particulate matter (PM10) into the environment, which has generated safety concerns about its potential health impact. DESIGN: Plasmid scission assay was performed using PM10 collected from moxibustion clinics. METHODS: PM10 was collected in winter 2012 by burning three types of moxa floss samples in moxibustion simulation clinics, and the resulting PM10 mass concentration was calculated. Oxidative capacity of the PM10 samples was measured by plasmid scission assay and the percentage of DNA damage at dosage 500 µg ml(-1) (D500) was calculated by linear regression analysis. RESULTS: The average PM10 mass concentration of samples A (3 years and 3:1 ratio), B (3 years and 8:1 ratio) and C (10 years and 3:1 ratio) was 273.33, 172.22 and 168.89 µg/m(3), respectively. The D500 oxidative capacity of PM10 was on average 24.25%, 27.83% and 28.07% for samples A, B and C, respectively. No significant difference was found in the PM10-induced oxidative damage by moxa smoke produced from the three types of moxa floss. CONCLUSIONS: PM10 mass concentrations from the three types of moxa floss combustion exceeded internationally recommended levels. Despite so, PM10 mass concentration of moxa smoke was much lower than biomass and coal combustion and similar to that of gas combustion. The oxidative DNA damage induced by individual PM10 in moxibustion environment was lower than that reported in other environments, indicating that moxibustion-derived PM10 might not be as injurious to human health as generally assumed.

Age-related changes in the location of the mandibular and mental foramen in children with Mongoloid skeletal pattern.

AIM: To observe age-related changes in the locations of mandibular foramen (MF) and mental foramen (mf) using dental panoramic tomographs (DPTs). METHODS: Ethical approval was obtained for this retrospective study. Location of MF was related to the ramus and occlusal plane, while mf to (i) erupted primary molars (ii) unerupted premolar tooth germs (iii) vertical height at the body of the mandible. RESULTS: One hundred and sixty-five DPTs were obtained from children with Mongoloid skeletal pattern. The ethnic composition was 112 Malays and 53 Chinese children (Willems dental age = 5.2-16.0 years). At the horizontal plane, MF remained constant at middle mid-quadrant of the ramus (88 %) and vertical plane; 68 % located below and 40 % above the occlusal plane. At age 9 years and above, there was a significant tendency for MF to be located at the level of occlusal plane. The most common location of mf was related to (i) erupted primary molars, mesial root of second primary molar (38 %); (ii) unerupted premolars tooth germs, between the apices of first and second premolar (44 %); and (iii) proportional vertical height to the mandible, middle third (52 %). At age 11 years and above, a significant tendency of mf to be located at the middle third of the body of mandible was observed. CONCLUSIONS: With advancing age and growth, the position of MF remained constant at the ramus with tendency to move from below to at the level of occlusal plane, while mf moved distally and inferiorly.

Enhanced dissolution of gallstone by combining ethanol with two commonly used cholelitholytic solvents.

BACKGROUND/AIMS: Contact dissolution therapy is one of the non-surgical treatments for patients with gallstone. Among the various solvents, methyl tert-butyl ether (MTBE) is used for cholesterol gallstone, while tetrasodium ethyl-dimethyl tetraacetate (EDTA-4Na) solution is used to dissolve calcium bilirubinate stones. However, the contents of gallstone cannot be precisely predicted while they are still present in the human body. This study was designed to test if the MTBE and EDTA can be mixed together and to test the solubility of different kinds of gallstone in each original solution and mixture. METHODOLOGY: Each 0.1 gm of mixed cholesterol stone, brown stone and pigment stone from 18 patients was used. Pure ethanol was chosen to enhance the miscibility between the organic phase of MTBE and the aqueous phase of EDTA. The contents of gallstone after dissolution were examined with scanning electromicroscopy. RESULTS: We found the mixture of ethanol, MTBE and EDTA to be the most efficient solvent in gallstone dissolution in comparison with the other two original solvents. The mixture reached a dissolution percentage of 97.96 +/- 1.00, 88.96 +/- 6.51 and 67.75 +/- 14.26 for cholesterol, brown and black pigment gallstone, respectively. CONCLUSIONS: We concluded that ethanol can be used to mix the MTBE and EDTA with good preservation in their litholytic effects on gallstone. The ethanol-MTBE-EDTA solvent is, therefore, a promising universal cholelitholytic agent which deserves further tests for its safety and efficacy in the in vivo study.

The pattern of lymphoma in east Malaysian patients as experienced in the University Hospital, Kuala Lumpur.

Lymphoma is a highly heterogeneous group of malignant disease. This study aimed to elucidate the pattern of lymphoma in the East Malaysian patient population. 107 cases of confirmed lymphomas from East Malaysian biopsy material were retrieved from the files of the Department of Pathology, University of Malaya, in the 3-year period between 1981 to 1983. With the use of a panel of lymphoid antibodies, the disease was sub-classified using the Rye classification for Hodgkin's lymphoma (HL) and the REAL classification for non-Hodgkin's lymphoma (NHL). All of the cases were tested for the presence of the Epstein-Barr virus by EBER-ISH. There were 11 (10.3%) HL, 80 (74.7%) B-NHL and 16 (15%) T-NHL. The HL:NHL ratio was 1:9. The most common tumour in children was Burkitt's lymphoma 7/13 (53.8%). In the adult group, there were 72/94 (76.6%) B-NHL ¿diffuse large cell type 51 (of which 2 were CD30+), Burkitt's lymphoma 8, follicular lymphoma 5, low grade MALT 2, mantle cell type 1 and not otherwise specified due to poor morphology 5¿, 13/94 (13.8%) T-NHL and 9/94 (9.6%) HL. Of the 9 adult HL, the most common subtype was nodular sclerosis (6, 66.7%). The EBER positive rate in classical HL, T-NHL, BL and B-NHL were 33.3%, 56.3%, 60.0% and 3.1% respectively. In conclusion, the spectrum of lymphoma seen in East Malaysia was rather similar to West Malaysia except for the very low prevalence of peripheral T-cell lymphoma (PTCL) in Sarawak (3.3%).

Rituximab as first-line treatment for the management of adult patients with non-severe hemophilia A and inhibitors.

BACKGROUND: The role of immunosuppression in the management of patients with congenital hemophilia and inhibitors is uncertain. The use of rituximab has been limited to case reports and case series. In most reports, rituximab was used as second-line or third-line treatment following failure of conventional immune tolerance induction therapy, and more commonly in pediatric patients. OBJECTIVES: The objective of this study was to describe our experience with rituximab for the eradication of factor VIII inhibitors in adult patients with non-severe hemophilia A. PATIENTS: We retrospectively reviewed the medical records of adult patients with non-severe hemophilia A and a diagnosis of FVIII inhibitor treated with rituximab (four weekly doses of 375 mg m(-2) ) as first-line treatment at our hemophilia center. RESULTS: We identified nine consecutive adult patients with hemophilia A (moderate, n = 5; mild, n = 4) at our institution between 2000 and 2013, with a median age of 54 years (range, 24-77 years) at the time of inhibitor diagnosis. No patient received concomitant immune tolerance induction therapy. All nine patients had successful eradication of FVIII inhibitors. The median time from the first dose of rituximab to a clinical response was 95 days (range, 12-278 days). The median follow-up was 56 months (range, 13-139 months). Following inhibitor eradication, eight patients were rechallenged with FVIII concentrates. Two patients developed inhibitor recurrence associated with surgery. CONCLUSION: This case series demonstrates that rituximab is a useful first-line treatment to achieve sustained inhibitor eradication in adult patients with non-severe hemophilia A.

Relationship between family meals away from home and nutritional status of adolescents.

INTRODUCTION: Despite the many benefits of family meals, data on association between family meals away from home (FMAFH) and nutritional status of adolescents is limited. This study determined the association between FMAFH with dietary intake and body mass index of adolescents (N = 408). METHODS: Data were obtained through interviewer-administered questionnaire and anthropometric measurements of adolescents. RESULTS: Respondents comprised 53.7% females, 67.6% Chinese with the mean age of sample being 13.7 +/- 0.6 years old. Generally, male adolescents had higher intakes of energy, macronutrients and micronutrients. All nutrients except calcium (51.3%), iron (females--54.7%) and vitamin A (females--86.1%) met the recommended intakes. A higher proportion of male (25.4%) than female (13.6%) adolescents were overweight and obese. About 44% of respondents had family meals > or = 7 times in the previous week with 48.9% reported having family meals at home > or = 7 times weekly. The majority (91.2%) of adolescents had FMAFH at least once a week either at restaurants (53%), fast food outlets (41.6%), food courts in shopping complexes (40%) or food stalls (30.2%). As the frequency of FMAFH increased, there was an increasing trend in energy and energy-adjusted nutrient intakes. However, only energy-adjusted fat intake was significantly high (p < 0.05) in adolescents having FMAFH > 7 times weekly. No significant association was observed for frequency of FMAFH and body mass index. CONCLUSION: With increasing dependence on foods outside the home, FMAFH can be a source of healthy diet for families provided they have the knowledge, skills and motivation to make healthy food choices.

Allergic rhinitis: evidence-based practice.

Allergic rhinitis is a common condition in Singapore, with a considerable disease burden. This article reviews the latest evidence-based concepts and current understanding of the disease, including its aetiology, pathogenesis, signs and symptoms, investigations as well as management. Particular attention is given to reviewing principles that will aid the management of this disease from a practical point of view, and the latest evidence for the various pharmacological options as well as immunotherapy is discussed. The article should be of interest to otolaryngologists as well as allergists, respiratory physicians and family practitioners.