An early report of exoscope-assisted otologic surgery.

BACKGROUND: Exoscope has been used in otoneurologic surgery in several reports. However, most ear surgeries are performed using either microscope or endoscopy today. The purpose of this study is to present our subjective and objective experience of using this instrument in our institution. METHODS: Sixteen ears with different severity and condition in 15 consecutive patients were enrolled. A questionnaire with 12 questions was sent to different participants, including surgeons, residents, medical students, and scrub nurses in the operation room. The total score and average score of each item were calculated and analyzed. RESULTS: Exclusive exoscopic operation was performed on 13 patients with 14 procedures. A combination of endoscopy-exoscope and microscope-exoscope was used in one patient, respectively. There were no complications. Hearing recovery or disease extirpation was achieved in most patients. Twenty participants in the operation room filled out the questionnaire. There was no significant difference between the different groups. High ratings were reported in terms of image quality, stereoscopic effects, magnification rate, and the same field of view as the surgeon. Worse ratings were reported in items related to limited working space, increase in eye strain by video observation, and focusing difficulty. CONCLUSION: Exoscopic ear surgery is feasible, safe, and effective in managing various otologic conditions involving external ear, middle ear, mastoid, and lateral skull base. Its high-definition image quality, stereoscopic effects, sufficient magnification, reliability and teaching value made it a potential instrument in general ear surgeries. Further improvements to current drawbacks can be anticipated.

Self-induced panniculitis in adolescence: Three cases and review of the literature.

Self-induced trauma is a rare cause of panniculitis in adolescents and may be associated with undiagnosed underlying psychological conditions. The condition often poses a diagnostic challenge as patients usually present with non-specific signs and symptoms, and often a concealed history of self-induced trauma. Here, we present three adolescent patients with self-induced traumatic panniculitis. All three patients were repeatedly admitted with non-specific cutaneous lesions as well as multiple somatic complaints. After extensive evaluation to exclude organic causes, psychiatric assessment eventually revealed underlying psychosomatic disorders as a cause of the self-induced trauma.

An allied reprogramming, selection, expansion and differentiation platform for creating hiPSC on microcarriers.

OBJECTIVES: Induced pluripotent stem cells (iPSCs) generated by monolayer cultures is plagued by low efficiencies, high levels of manipulation and operator unpredictability. We have developed a platform, reprogramming, expansion, and differentiation on Microcarriers, to solve these challenges. MATERIALS AND METHODS: Five sources of human somatic cells were reprogrammed, selected, expanded and differentiated in microcarriers suspension cultures. RESULTS: Improvement of transduction efficiencies up to 2 times was observed. Accelerated reprogramming in microcarrier cultures was 7 days faster than monolayer, providing between 30 and 50-fold more clones to choose from fibroblasts, peripheral blood mononuclear cells, T cells and CD34+ stem cells. This was observed to be due to an earlier induction of genes (ß-catenin, E-cadherin and EpCAM) on day 4 versus monolayer cultures which occurred on days 14 or later. Following that, faster induction and earlier stabilization of pluripotency genes occurred during the maturation phase of reprogramming. Integrated expansion without trypsinization and efficient differentiation, without embryoid bodies formation, to the three germ-layers, cardiomyocytes and haematopoietic stem cells were further demonstrated. CONCLUSIONS: Our method can solve the inherent problems of conventional monolayer cultures. It is highly efficient, cell dissociation free, can be operated with lower labor, and allows testing of differentiation efficiency without trypsinization and generation of embryoid bodies. It is also amenable to automation for processing more samples in a small footprint, alleviating many challenges of manual monolayer selection.

Selection of O-negative induced pluripotent stem cell clones for high-density red blood cell production in a scalable perfusion bioreactor system.

OBJECTIVES: Large-scale generation of universal red blood cells (RBCs) from O-negative (O-ve) human induced pluripotent stem cells (hiPSCs) holds the potential to alleviate worldwide shortages of blood and provide a safe and secure year-round supply. Mature RBCs and reticulocytes, the immature counterparts of RBCs generated during erythropoiesis, could also find important applications in research, for example in malaria parasite infection studies. However, one major challenge is the lack of a high-density culture platform for large-scale generation of RBCs in vitro. MATERIALS AND METHODS: We generated 10 O-ve hiPSC clones and evaluated their potential for mesoderm formation and erythroid differentiation. We then used a perfusion bioreactor system to perform studies with high-density cultures of erythroblasts in vitro. RESULTS: Based on their tri-lineage (and specifically mesoderm) differentiation potential, we isolated six hiPSC clones capable of producing functional erythroblasts. Using the best performing clone, we demonstrated the small-scale generation of high-density cultures of erythroblasts in a perfusion bioreactor system. After process optimization, we were able to achieve a peak cell density of 34.7 million cells/ml with 92.2% viability in the stirred bioreactor. The cells expressed high levels of erythroblast markers, showed oxygen carrying capacity, and were able to undergo enucleation. CONCLUSIONS: This study demonstrated a scalable platform for the production of functional RBCs from hiPSCs. The perfusion culture platform we describe here could pave the way for large volume-controlled bioreactor culture for the industrial generation of high cell density erythroblasts and RBCs.

Merocel compression dressing: a novel modified surgical technique for treating auricular pseudocyst.

PURPOSE: Auricular pseudocyst (AP) is a benign, noninflammatory swelling to the ear, located on either the front or side surface. Deroofing surgery with variable compression methods is considered the most effective method. However, post-operative wound pain is the main drawback following compression. We are introducing a novel painless surgical procedure which involves deroofing technique followed by Merocel® compression dressing. METHODS: From 2015 to 2020, thirty-one patients with AP received this new surgical compression method in our university-affiliated tertiary hospital. Retrospective chart review and the analysis of the results were conducted. RESULTS: All patients had unilateral lesions, with left side lesions (58.1%) predominant. The concha cymba (38.7%) and concha cavum (35.8%) were the most common sites. Previous aspiration or drainage had been performed for the cysts in eight patients (25.8%). Only one patient had the recurrence after post-operative 3 months and received the revised surgery without following recurrence and discomfort. Among all patients, 29 (93.5%) patients claimed minimal pain around 0 or 1 in numeric rating scale of pain score. Three patients had mild ecchymosis but recovered after conservative treatment. One patient had mild auricular deformity after surgery due to pre-treatment partial cartilage necrosis. All patients had follow-up for at least 6 months. CONCLUSION: This novel Merocel® compression dressing technique to treat AP after deroofing is an effective procedure. Minimal pain, simple to do and easily acquired materials were the advantages of this novel procedure.

Integrating Human-Induced Pluripotent Stem Cell Expansion Capability and Cardiomyocyte Differentiation Potential in a Microcarrier Suspension Culture.

Human-induced pluripotent stem cells are known for their high proliferation capacity as well as their ability to differentiate to different lineages (Ban et al., Theranostics 7(7):2067-2077, 2017; Chen et al., Stem Cell Res 15(2):365-375, 2015; Serra et al., Trends Biotechnol 30(6):350-359, 2012). For stem-cell-derived cardiomyocytes to evolve into a scalable therapeutic source, a large quantity of highly pure cardiomyocytes is needed. Thus, lies the challenge of defining an efficient cardiomyocyte differentiation process. This chapter describes a method to evaluate multiple human-induced pluripotent stem cell lines for their cardiac differentiation potentials before evaluating their integrated proliferation and differentiation abilities in microcarrier cultures in a spinner culture format.

Juvenile xanthogranulomas in Asian children.

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytic disorder. It can rarely be associated with systemic involvement. There is a paucity of literature on JXG in Asian children. We aim to describe the epidemiology, clinical features, systemic associations, histological features and outcome of a cohort of Asian children with JXG, and review the literature on the condition. We retrospectively reviewed the demographic, clinical and histological data of patients less than 16 years of age, diagnosed with JXG at our tertiary pediatric hospital between January 2002 and April 2019. A total of 147 children with JXG were identified, with a slight male preponderance of 53.1%. The median age of the onset was 15.5 months, with 69.4% presenting before 2 years of age. There was no racial predilection. The most frequently involved site was the head and neck region (44.2%). The majority of patients (76.2%) presented with a solitary lesion. Spontaneous resolution was documented in 57.7% of our patients with mean duration to resolution of 18.8 months. The proportion and speed of resolution did not differ in children with single or multiple lesions. No ophthalmologic complications were detected in our study cohort. JXG in children is generally limited to the skin and is rarely associated with systemic involvement, including the eye. Unless clinically indicated, the results from our study does not support routine screening for juvenile myelomonocytic leukemia, eye or systemic complications, even in the setting of multiple cutaneous JXGs.

Moisturisers from birth in at-risk infants of atopic dermatitis - a pragmatic randomised controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a common, chronic dermatosis, with onset of disease often manifesting in early infancy. Past studies evaluating the early use of moisturisers in the prevention of AD had mixed results. OBJECTIVES: To compare the incidence of moderate or severe AD and total incidence of AD in a cohort of 'at-risk' infants treated with moisturisers from the first 2 weeks of life, to a similar group without moisturisers. METHODS: We performed a single-centre, prospective, parallel-group, randomised study in infants with at least 2 first-degree relatives with atopy. Subjects were randomised into either a treatment group with moisturisers or a control group without moisturisers. Participants were assessed at 2, 6, and 12 months for AD and if present, the severity was assessed using SCORAD index. We also compared the overall incidence of AD, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, pH, and incidence of food and environmental sensitisation and allergies between both groups. Genotyping for loss-of-functions mutations in the FLG gene was conducted. RESULTS: A total of 200 subjects were recruited, with 100 subjects in each arm. There was no significant difference in incidence of moderate or severe AD, and total incidence of AD at 12 months between the treatment and control groups. There was a lower mean SCORAD in the treatment group than in the control group, but no significant difference in TEWL, SC hydration, and skin pH. No significant side-effects were reported. CONCLUSIONS: The early use of moisturisers in 'at-risk' infants does not reduce the incidence of moderate-to-severe AD and overall incidence of AD in infancy.

Transcervical Transtracheal Resection of Cervical Esophageal Smooth Muscle Tumor.

Cervical esophageal smooth muscle tumors are traditionally resected via lateral transcervical with or without video-assisted thoracoscopic approaches. Exposure is frequently limited, however, with risks of recurrent laryngeal nerve and posterior tracheal wall injury and jeopardization of cervical tracheal and cervical esophageal blood supply. We herein describe an anterior transcervical transtracheal approach to counter some of the aforementioned problems and avoid morbidities associated with thoracoscopic surgery when resecting smooth muscle tumors arising from the cervical esophagus.

Tracheostomy during COVID-19 pandemic-Novel approach.

BACKGROUND: This study describes a novel approach in reducing SARS-CoV-2 transmission during tracheostomy. METHODS: Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented. RESULTS: Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%-100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%-10.0%) and 3.3% (6.7%-10.0%), respectively. No droplet contamination was noted on all face shields. CONCLUSION: Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.

Clinical characteristics and treatment outcome of adenoid cystic carcinoma in the external auditory canal.

BACKGROUND: This study reviewed the clinical manifestations, pathological findings, and treatment outcomes of adenoid cystic carcinoma (ACC) in the external auditory canal (EAC). METHODS: This was a retrospective review of 12 patients with a diagnosis of ACC in the EAC seen in a single institution over a 30-year period. Data on the demographics, clinical presentation, treatment strategy, and outcome, as well as the pathological features of ACC, were reviewed and analyzed. RESULTS: The male-to-female ratio was 1:3 and the mean patient age was 55.9 years. The most common clinical presentation was otalgia (75%). Ten patients underwent surgical interventions, including radical mastoidectomy in five patients, wide excision in three, and lateral temporal bone resection in two. Adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT) was performed in case of incomplete resection. Two patients underwent non-surgical treatments: radiotherapy in one and CCRT in the other. Microscopic perineural invasion was not associated with otalgia or histological subtype. The mean follow-up period was 84.6 months. Local recurrence occurred in 33% of patients. One-quarter of patients had distant metastasis, and all had lung metastasis. The 5-year overall survival rate for these patients was 82.5%. CONCLUSION: EAC ACC should be included in the differential diagnosis when a patient presents with otalgia and a mass in EAC for more than 6 months, particularly if the patient is a middle-aged female. Otalgia might not be associated with perineural invasion or histological subtype. The lung is the most common site of distant metastasis in patients with EAC ACC. Further studies should determine the optimal treatment protocol for this rare malignancy.

Comparing the Potential for Irritation of a Ceramide-Based Moisturizer with a Urea-Based Moisturizer for Pediatric Atopic Dermatitis.

INTRODUCTION: Moisturizers are one of the mainstays of the topical treatment of atopic dermatitis (AD). One of the adverse effects of moisturizers is skin irritation, especially on excoriated AD skin. We compared the potential for irritation of two commercially available moisturizer products for the treatment of AD: a ceramide-based moisturizer (Ceradan® Cream; Hyphens Pharma Pte Ltd, Singapore) and a urea 5% moisturizer (Aqurea Lite Cream; ICA Pharma Pte Ltd, Singapore). METHODS: We performed a prospective single-blind randomized controlled study recruiting AD patients aged between 8 and 16 years with symmetrical or near symmetrical scratch marks (excoriations) of at least grade 2 to 3 severity score, according to the Eczema Area and Severity Index (EASI), over bilateral antecubital fossae. Subjects were randomized to receive the ceramide-based moisturizer to either the left or right antecubital fossa or urea 5% cream to the other antecubital fossa. Subjects were asked to grade the immediate skin irritation of both creams on a standard visual analogue scale (VAS) and which cream they would prefer to use as a daily moisturizer. Primary outcome was the mean irritant score of each cream, and secondary outcome was the subjects' preference of either cream as their daily moisturizer. RESULTS: A total of 42 participants were enrolled with a mean age of 11 years 5 months. The ceramide-based cream had a significantly lower mean VAS score (mean 0.69, SD = 1.63) for irritation compared with urea 5% cream (1.43, SD = 1.64) (p = 0.035). More participants also preferred the ceramide-based cream over urea 5% cream (62% versus 38%) as their daily moisturizer, but this did not reach statistical significance (p = 0.164). CONCLUSIONS: A ceramide-based moisturizer may be considered as a suitable choice for children to minimize irritation from moisturizer treatment for AD.

Conservation of personal protective equipment for head and neck cancer surgery during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery. METHODS: Fifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented. RESULTS: Forty-five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery. CONCLUSION: Face shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.

Selection of human induced pluripotent stem cells lines optimization of cardiomyocytes differentiation in an integrated suspension microcarrier bioreactor.

BACKGROUND: The production of large quantities of cardiomyocyte is essential for the needs of cellular therapies. This study describes the selection of a human-induced pluripotent cell (hiPSC) line suitable for production of cardiomyocytes in a fully integrated bioprocess of stem cell expansion and differentiation in microcarrier stirred tank reactor. METHODS: Five hiPSC lines were evaluated first for their cardiac differentiation efficiency in monolayer cultures followed by their expansion and differentiation compatibility in microcarrier (MC) cultures under continuous stirring conditions. RESULTS: Three cell lines were highly cardiogenic but only one (FR202) of them was successfully expanded on continuous stirring MC cultures. FR202 was thus selected for cardiac differentiation in a 22-day integrated bioprocess under continuous stirring in a stirred tank bioreactor. In summary, we integrated a MC-based hiPSC expansion (phase 1), CHIR99021-induced cardiomyocyte differentiation step (phase 2), purification using the lactate-based treatment (phase 3) and cell recovery step (phase 4) into one process in one bioreactor, under restricted oxygen control (< 30% DO) and continuous stirring with periodic batch-type media exchanges. High density of undifferentiated hiPSC (2 ± 0.4 × 106 cells/mL) was achieved in the expansion phase. By controlling the stirring speed and DO levels in the bioreactor cultures, 7.36 ± 1.2 × 106 cells/mL cardiomyocytes with > 80% Troponin T were generated in the CHIR99021-induced differentiation phase. By adding lactate in glucose-free purification media, the purity of cardiomyocytes was enhanced (> 90% Troponin T), with minor cell loss as indicated by the increase in sub-G1 phase and the decrease of aggregate sizes. Lastly, we found that the recovery period is important for generating purer and functional cardiomyocytes (> 96% Troponin T). Three independent runs in a 300-ml working volume confirmed the robustness of this process. CONCLUSION: A streamlined and controllable platform for large quantity manufacturing of pure functional atrial, ventricular and nodal cardiomyocytes on MCs in conventional-type stirred tank bioreactors was established, which can be further scaled up and translated to a good manufacturing practice-compliant production process, to fulfill the quantity requirements of the cellular therapeutic industry.

Vulvar lymphangiectasia secondary to gastrointestinal tuberculosis infection in a teenager.

We report a rare presentation of vulvar lymphangiectasia that developed secondary to gastrointestinal tuberculosis in a teenager, and its spontaneous resolution after anti-tuberculous treatment was completed.

Rumpel-Leede Phenomenon-An alarming rash with benign etiology in 4 healthy infants.

The Rumpel-Leede phenomenon (RLP) is a rare clinical presentation and in some cases shown to be related to serious systemic conditions. In children, it has been described in association with idiopathic thrombocytopenic purpura and Henoch-Schönlein purpura. We present a series of pediatric cases of RLP with mechanical etiologies that had a benign course. We propose minimal investigations for pediatric RLP cases who are systemically well and have a clear suggestive history of a mechanical cause.

Factors influencing quality of life in children with atopic dermatitis and their caregivers: a cross-sectional study.

Better understanding of atopic dermatitis' effect on quality of life could enhance current management and therapeutic strategies. Studies investigating factors related to the health-related quality of life (HRQOL) of children with atopic dermatitis and their caregivers are limited. This cross-sectional study included 559 children (<16 years) with atopic dermatitis and their caregivers. Disease severity was associated with infants' HRQOL (moderate: IRR: 1.42, 95% CI 1.20-1.67; severe: IRR: 1.72, 95% CI 1.32-2.24). Age and disease severity were associated with children's HRQOL (age: IRR: 0.99, 95% CI 0.98-1.00; moderate: IRR: 1.08, 95% CI 1.02-1.14). Quality of life subdomains itching/scratching, emotional distress and sleep disturbance were most reported and increased with higher disease severity. Both caregivers' mental and physical health were negatively affected by children's HRQOL (physical: IRR: 0.99, 95% CI 0.99-1.00; mental: IRR: 0.98, 95% CI 0.97-0.99). Sociodemographic characteristics (gender, ethnicity, educational attainment of carers, number of children) did not demonstrate significance in children's HRQOL model. In conclusion, current atopic dermatitis diagnostics and treatment have to be extended to the factors influencing both children' as their caregivers' quality of life and adapting management accordingly. Itching/scratching, emotional distress and sleep disturbance deserve attention. Sociodemographic characteristics in children's HRQOL models also merit attention in further research.

Simultaneous auricular reconstruction and transcutaneous bone conduction device implantation in patients with microtia.

BACKGROUND/PURPOSE: The Bonebridge (BB) is a newly designed transcutaneous bone conduction hearing implant. We describe, for the first time, simultaneous BB implantation and different surgical techniques of auricular reconstruction for microtia patients with aural atresia/stenosis. METHODS: Ten patients with unilateral or bilateral microtia underwent BB implantation combined simultaneously with either total auricular reconstruction using bespoke hand-carved Medpor framework or second stage auricular projection using autologous costal cartilage framework. Auditory aided and unaided sound fields were evaluated using (1) a pure-tone average (PTA4), (2) a speech reception threshold (SRT), and (3) a Speech Discrimination Score (SDS) at a sound level of 65 dB SPL. RESULTS: All patients and their families were satisfied with the aesthetic outcome of their constructed ears with no requests for further revision. No major complications were encountered. One patient developed minor partial skin graft epidermolysis that healed uneventfully, and another patient had a three month period of auditory acclimatization to the BB device that resolved. Postoperatively, the mean aided PTA4 decreased by 35.35 dB, while the SRT was 54.5 dB HL unaided and 28 dB HL with use of a BB sound processor. The SDS increased by 16.4%-65 dB SPL. CONCLUSION: Simultaneous BB implantation during either total auricular reconstruction or framework projection for microtia patients who have aural atresia/stenosis is feasible and safe. This approach reduces operative stages, thereby minimizing schooling/occupational disruption and time to total microtia reconstruction and auditory rehabilitation.