Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects.

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.

Carica papaya L. Leaf: A Systematic Scoping Review on Biological Safety and Herb-Drug Interactions.

INTRODUCTION: The Carica papaya L. leaf is gaining interest as a potential therapeutic agent for alleviating dengue- and non-dengue-associated thrombocytopaenia. In that regard, safety considerations are as important as efficacy potential. The safety evaluation of botanical products for human use is complicated by variable formulations, complex phytochemical composition, and extrinsic toxicants. This review aimed to systematically collate related safety clinical and preclinical data, as well as reports on herb-drug interactions of C. papaya leaf consumption. METHODS: A systematic search using predetermined keywords on electronic databases (MEDLINE, Cochrane Library Central, LILACS, and Web of Science) and grey literature was conducted. Relevant clinical and preclinical studies were identified, screened, and analysed to present an overall safety profile of C. papaya leaf consumption. RESULTS: A total of 41 articles were included (23 clinical, 5 ongoing trials, and 13 preclinical) for descriptive analysis on study characteristics, adverse reactions, toxicity findings, and herb-drug interactions, from which 13 randomised controlled and quasiexperimental trials were further assessed for risk of bias and reporting quality. Overall, C. papaya leaf consumption (in the form of juice and standardised aqueous extract) was well tolerated by adult humans for short durations (

Patterns of middle-ear cholesteatoma and implications for surgical approach.

OBJECTIVES: Understanding the pattern of middle-ear cholesteatoma becomes pertinent with the rise of endoscopic surgery as surgeons decide on the optimal approach to visualise and extirpate disease. With modifications to the Telmesani attic-tympanum-mastoid staging system, this study aimed to evaluate the commonest patterns of middle-ear cholesteatoma and their implications for surgical approach. METHODS: A retrospective study was conducted in a single tertiary institution in Singapore. All patients undergoing cholesteatoma surgery between January 2012 and June 2015 were included. Staging of cholesteatoma was based on clinical assessment corroborated by radiological findings. RESULTS: Out of the 55 ears included, 98.2 per cent had cholesteatoma involving the attic. The disease extended into the mastoid antrum and beyond in 43 cases (78.2 per cent). The facial recess and/or sinus tympanum was affected in 26 cases (47.3 per cent). CONCLUSION: The majority of cholesteatoma cases present with extensive attic disease and significant mastoid involvement. In these cases, endoscopes may be best suited to adjunctive rather than exclusive use in surgery.

Surgical management of pulsatile tinnitus secondary to jugular bulb or sigmoid sinus diverticulum with review of literature.

INTRODUCTION: Jugular bulb and sigmoid sinus anomalies are well-known causes of vascular pulsatile tinnitus. Common anomalies reported in the literature include high-riding and/or dehiscent jugular bulb, and sigmoid sinus dehiscence. However, cases of pulsatile tinnitus due to diverticulosis of the jugular bulb or sigmoid sinus are less commonly encountered, with the best management option yet to be established. In particular, reports on surgical management of pulsatile tinnitus caused by jugular bulb diverticulum have been lacking in the literature. OBJECTIVES: To report two cases of pulsatile tinnitus with jugular bulb and/or sigmoid sinus diverticulum, and their management strategies and outcomes. In this series, we describe the first reported successful case of pulsatile tinnitus due to jugular bulb diverticulum that was surgically-treated. SUBJECTS AND METHODS: Two patients diagnosed with either jugular bulb and/or sigmoid sinus diverticulum, who had presented to the Otolaryngology clinic with pulsatile tinnitus between 2016 and 2017, were studied. Demographic and clinical data were obtained, including their management details and clinical outcomes. RESULTS: Two cases (one with jugular bulb diverticulum and one with both sigmoid sinus and jugular bulb diverticula) underwent surgical intervention, and both had immediate resolution of pulsatile tinnitus post-operatively. This was sustained at subsequent follow-up visits at the outpatient clinic, and there were no major complications encountered for both cases intra- and post-operatively. CONCLUSION: Transmastoid reconstruction/resurfacing of jugular bulb and sigmoid sinus diverticulum with/without obliteration of the diverticulum is a safe and effective approach in the management of bothersome pulsatile tinnitus arising from these causes.

Micro-textured films for reducing microbial colonization in a clinical setting.

BACKGROUND: Transmission of microbes in the hospital environment occurs frequently through human interactions with high-touch surfaces such as patient beds and over-bed tables. Although stringent cleaning routines are implemented as a preventive measure to minimize transmission of microbes, it is desirable to have high-touch surfaces made of antimicrobial materials. Physical texturing of solid surfaces offers a non-bactericidal approach to control the colonization of such surfaces by microbes. AIM: To investigate the efficacy of micro-textured polycarbonate films in reducing bacterial load on over-bed tables in a hospital ward. METHODS: Two different micro-patterns were fabricated on polycarbonate film via a thermal imprinting method. Micro-textured films were then mounted on patient over-bed tables in a general hospital ward and the bacterial load monitored over 24 h. Total colony counts, which represented on-specific bacterial loading, and meticillin-resistant Staphylococcus aureus counts were monitored at each time-point. FINDINGS: Over a period of 24 h, both micro-textured surfaces showed consistently lower bacterial load as compared to the unpatterned polycarbonate and the bare over-bed table laminate. This study supports the findings of earlier laboratory-scale studies that microscale physical texturing can reduce bacterial colonization on a solid surface. CONCLUSION: Results of the current study suggest that micro-textured surfaces could provide a viable method for reducing microbial contamination of high-touch surfaces in hospitals.

MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia.

BACKGROUND AND PURPOSE: MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia. MATERIALS AND METHODS: MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the χ2 test. RESULTS: The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas. CONCLUSIONS: MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

Skull base osteomyelitis secondary to malignant otitis externa mimicking advanced nasopharyngeal cancer: MR imaging features at initial presentation.

PURPOSE: Skull base osteomyelitis (SBOM) is an inflammatory process which often arises from malignant otitis externa (MOE); the diffuse skull base and adjacent soft tissue involvement may be mistaken at initial imaging for advanced nasopharyngeal carcinoma (NPC), especially if there is no prior knowledge of MOE, direct spread from the sphenoid sinus or in atypical presentations of MOE. This study aims to evaluate imaging features on MR that may differentiate SBOM from NPC. MATERIALS AND METHODS: The MR examinations of 26 patients diagnosed with SBOM between January 1996 and January 2013 were retrospectively reviewed. Comparison was also made with the MR images of 22 consecutive patients with newly diagnosed advanced T3 and T4 NPC between July 2011 and August 2012. Imaging features in both conditions were compared, including the presence of a nasopharyngeal bulge, nasopharyngeal mucosal irregularity, lateral extension, architectural distortion (or lack thereof), increased T2 signal and enhancement patterns. RESULTS: The most prevalent findings in SBOM were lateral extension, increased T2 signal in adjacent soft tissues, lack of architectural distortion and enhancement greater than or equal to mucosa. The combination of these 4 findings was found to best differentiate SBOM from advanced NPC, and found to be statistically significant (p<0.001). CONCLUSION: We suggest that the combination of lateral extension, increased T2 signal, lack of architectural distortion and enhancement greater than or equal to mucosa is helpful in differentiating SBOM from advanced NPC.

Cochlear duct length-one size fits all?

OBJECTIVE: Recent studies demonstrated the utility of high-resolution computed tomography (HRCT) scans in measuring basal cochlear length and cochlear insertion depths. These studies showed significant variations in the anatomy of the cochlea amongst humans. The aim of our study was to investigate for gender and racial variations in the basal turn length of the human cochlea in an Asian population. METHOD: HRCT temporal bone data from year 1997 till 2012 of patients with normally developed cochleae who reported with otologic disease was obtained. Reconstruction of the full basal turn was performed for both ears. The largest distance from the midpoint of the round window, through the midmodiolar axis, to the lateral wall was measured (distance A). Length of the lateral wall of the cochlea to the first turn (360°) was calculated and statistically analyzed. RESULTS: HRCT temporal bone data from 161 patients was initially obtained. Four patients were subsequently excluded from the study as they were of various other racial groups. Study group therefore comprised of 157 patients (314 cochleae). Mean distance A was statistically different between the two sides of the ear (right 9.09mm; left 9.06mm; p=0.0069). Significant gender and racial differences were also found. Mean distance A was 9.17mm in males and 8.97mm in females (p=0.0016). The racial groups were Chinese (39%), Malay (38%) and Indian (22%). Between racial groups, mean distance A was 9.11mm (Chinese), 9.11mm (Malays) and 8.99mm (Indians). The mean basal turn lengths ranged from 19.71mm to 25.09mm. With gender factored in, significant variation in mean basal turn lengths was found across all three racial groups (p=0.04). CONCLUSION: The view of the basal turn of the cochlea from HRCT is simple to obtain and reproducible. This study found significant differences in basal cochlear length amongst male and female Asian patients, as well as amongst various racial groups. This has implications for cochlear electrode insertion as well as electrode array design.

Sinonasal angioleiomyoma.

BACKGROUND: Angioleiomyoma of the nasal cavity is an extremely rare benign neoplasm. It usually occurs in the lower extremities. Up to date, only few cases of angioleiomyoma have been reported. First case of angioleiomyoma of nasal cavity was reported in 1966. We report a rare case of angioleiomyoma arising from the right maxillary sinus. CASE REPORT: A 43-year-old lady presented with recurrent epistaxis and right nasal obstruction for two months duration. Clinical examination revealed a huge right nasal mass obstructing the right nasal cavity. The tumour was excised completely via endoscopic endonasal surgical approach. Histopathological examination confirmed the tumour is sinonasal angioleiomyoma. Postoperatively, she recovered well without any recurrence after a year of followup. CONCLUSION: This tumour has an excellent prognosis and recurrence is extremely rare if excised completely.

Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert® MTB/RIF?

BACKGROUND: Studies evaluating the role of transbronchial lung biopsy (TBLB) in diagnosing pulmonary tuberculosis (PTB) date back decades and have shaped current practice. However, with the recent advent of bronchoalveolar lavage (BAL) Xpert® MTB/RIF, it is time to re-evaluate the role of TBLB. OBJECTIVE: To assess the impact of BAL and TBLB with the addition of BAL Xpert on diagnostic PTB yields and time to treatment initiation in sputum-scarce or acid-fast bacilli (AFB) smear-negative PTB patients. METHODS: We retrospectively reviewed all sputum-scarce or AFB smear-negative patients who underwent both BAL and TBLB for suspected PTB between March 2011 and October 2013. Xpert was performed on all BAL specimens. RESULTS: Of 158 patients included in our analysis, 44 were culture-proven PTB. Ninety-four per cent of the patients had AFB smear-negative BAL samples. The sensitivity and specificity of Xpert in AFB smear-negative BAL samples were respectively 60% and 98%. The addition of BAL Xpert expedited the institution of PTB treatment while having diagnostic yields comparable to those of conventional BAL with TBLB. CONCLUSIONS: The use of BAL Xpert may obviate the need for TBLB in increasing the diagnostic yield of PTB in sputum-scarce or AFB smear-negative patients.

Results from the Survey of Antibiotic Resistance (SOAR) 2012-14 in Thailand, India, South Korea and Singapore.

OBJECTIVES: To provide susceptibility data for community-acquired respiratory tract isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis collected in 2012-14 from four Asian countries. METHODS: MICs were determined using Etest(®) for all antibiotics except erythromycin, which was evaluated by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide/clindamycin interpretation, breakpoints were adjusted for incubation in CO2 where available. RESULTS: Susceptibility of S. pneumoniae was generally lower in South Korea than in other countries. Penicillin susceptibility assessed using CLSI oral or EUCAST breakpoints ranged from 21.2% in South Korea to 63.8% in Singapore. In contrast, susceptibility using CLSI intravenous breakpoints was much higher, at 79% in South Korea and ∼95% or higher elsewhere. Macrolide susceptibility was ∼20% in South Korea and ∼50%-60% elsewhere. Among S. pyogenes isolates (India only), erythromycin susceptibility (∼20%) was lowest of the antibiotics tested. In H. influenzae antibiotic susceptibility was high except for ampicillin, where susceptibility ranged from 16.7% in South Korea to 91.1% in India. South Korea also had a high percentage (18.1%) of ß-lactamase-negative ampicillin-resistant isolates. Amoxicillin/clavulanic acid susceptibility for each pathogen (PK/PD high dose) was between 93% and 100% in all countries except for H. influenzae in South Korea (62.5%). CONCLUSIONS: Use of EUCAST versus CLSI breakpoints had profound differences for cefaclor, cefuroxime and ofloxacin, with EUCAST showing lower susceptibility. There was considerable variability in susceptibility among countries in the same region. Thus, continued surveillance is necessary to track future changes in antibiotic resistance.

Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.

Superior cervical ganglion mimicking retropharyngeal adenopathy in head and neck cancer patients: MRI features with anatomic, histologic, and surgical correlation.

INTRODUCTION: To describe the unique MRI findings of superior cervical ganglia (SCG) that may help differentiate them from retropharyngeal lymph nodes (RPLNs). METHODS: A retrospective review of post-treatment NPC patients from 1999 to 2012 identified three patients previously irradiated for NPC that were suspected of having recurrent nodal disease in retropharyngeal lymph nodes during surveillance MRI. Subsequent surgical exploration revealed enlarged SCG only; no retropharyngeal nodal disease was found. A cadaveric head specimen was also imaged with a 3T MRI before and after dissection. In addition, SCG were also harvested from three cadaveric specimens and subjected to histologic analysis. RESULTS: The SCG were found at the level of the C2 vertebral body, medial to the ICA. They were ovoid on axial images and fusiform and elongated with tapered margins in the coronal plane. T2-weighted (T2W) signal was hyperintense. No central elevated T1-weighted (T1W) signal was seen within the ganglia in non-fat-saturated sequences to suggest the presence of a fatty hilum. Enhancement after gadolinium was present. A central "black dot" was seen on axial T2W and post-contrast images in two of the three SCG demonstrated. Histology showed the central black line was comprised of venules and interlacing neurites within the central portion of the ganglion. CONCLUSIONS: The SCG can be mistaken for enlarged RPLNs in post-treatment NPC patients. However, there are features which can help differentiate them from RPLNs, preventing unnecessary therapy. These imaging findings have not been previously described.

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study.

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality.

Female ageing and reproductive outcome in assisted reproduction cycles.

INTRODUCTION: Fertility in women declines with increasing age. With the deferment of marriage and childbearing, couples are turning to assisted reproductive technology to counteract this decline. We aimed to evaluate the results of in vitrofertilisation (IVF)/intracytoplasmic sperm injection (ICSI) in women of different age groups, and highlight the cost-effectiveness of IVF treatment in these groups while assessing its implications on the national healthcare provision model. METHODS: Retrospective analysis of 3,412 stimulated IVF/ICSI cycles in a hospital-based IVF centre was performed from January 2008 to December 2010. Patients were stratified into seven age groups: < 30 years; 30-35 years; 36-37 years; 38 years; 39 years; 40-44 years; and ≥ 45 years. RESULTS: Age had a significant effect on the number of cycles leading to embryo transfer (p < 0.001). The number of oocytes retrieved decreased across the various age groups (p < 0.001) and was the highest among women aged < 30 (mean 18.5 ± 10.3) years. With increasing age, there was a trend toward a lower fertilisation rate. Age also had a significant effect on the rates of clinical pregnancy, live birth and multiple pregnancies (p < 0.001). CONCLUSION: Patients aged < 30 years had the best IVF outcomes, reflecting optimal reproductive capacity. Age-related decline in fertility starts after 30 years. Women opting for IVF should be counselled about age-specific success rates while taking into account individual risk factors.

Diagnosing features of Jacobson's nerve schwannoma.

Jacobson's nerve schwannoma is a rare middle ear tumour presenting as a mass along the cochlear promontory. It can be differentiated from other masses along the promontory based on clinical findings, and computed tomography and magnetic resonance imaging features. For small-sized masses, it is possible to differentiate the various middle ear schwannomas from one another. We present the case of a 40-year-old woman with a ten-year history of left hearing loss who was diagnosed with Jacobson's nerve schwannoma.