Prognostic impact of presenting symptoms of patients with hepatocellular carcinoma.

Introduction: It is not known if the nature, number and duration of presenting symptoms at diagnosis of hepatocellular carcinoma impact on overall survival. This study examines whether the presenting symptoms of hepatocellular carcinoma have a significant impact on prognosis. Methods: The study cohort comprised 725 patients with symptomatic hepatocellular carcinoma seen in our department since October 1983. Another 545 patients were diagnosed on surveillance or from incidental findings. Presenting symptoms at diagnosis were documented. A survival census was performed on 31 October 2015 with the national registry of deaths. Presenting symptoms were examined for association with overall survival using multivariable Cox regression analysis. Survival analysis was done by Kaplan-Meier method with log-rank testing. Bivariate Pearson correlation was used to look for any association between duration of symptoms and overall survival. Results: Patients with symptomatic hepatocellular carcinoma had a significantly shorter survival than those diagnosed incidentally or on screening (94.0 vs. 786.0 days, P < 0.001). Survival was shorter in patients presenting with fluid retention (56.0 vs. 118.0 days, P < 0.001), jaundice (48.0 vs. 94.0 days, P = 0.017) and two or more symptoms (P = 0.010). Pain was associated with better survival (P < 0.001). On multivariable Cox regression analysis, only fluid retention (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.30-1.87) and jaundice (HR 1.36, 95% CI 1.07-1.74) were independently associated with shorter survival. There was no significant relationship between the duration of symptoms and overall survival. Conclusion: Patients with hepatocellular carcinoma who present with fluid retention or jaundice have significantly shorter overall survival. This is useful in assessing patients at the time of diagnosis.

Endoscopic retrograde cholangiopancreatography-related complications: risk stratification, prevention, and management

Endoscopic retrograde cholangiopancreatography (ERCP) plays a crucial role in the management of pancreaticobiliary disorders. Although the ERCP technique has been refined over the past five decades, it remains one of the endoscopic procedures with the highest rate of complications. Risk factors for ERCP-related complications are broadly classified into patient-, procedure-, and operator-related risk factors. Although non-modifiable, patient-related risk factors allow for the closer monitoring and instatement of preventive measures. Post-ERCP pancreatitis is the most common complication of ERCP. Risk reduction strategies include intravenous hydration, rectal nonsteroidal anti-inflammatory drugs, and pancreatic stent placement in selected patients. Perforation is associated with significant morbidity and mortality, and prompt recognition and treatment of ERCP-related perforations are key to ensuring good clinical outcomes. Endoscopy plays an expanding role in the treatment of perforations. Specific management strategies depend on the location of the perforation and the patient’s clinical status. The risk of post-ERCP bleeding can be attenuated by preprocedural optimization and adoption of intra-procedural techniques. Endoscopic measures are the mainstay of management for post-ERCP bleeding. Escalation to angioembolization or surgery may be required for refractory bleeding. Post-ERCP cholangitis can be reduced with antibiotic prophylaxis in high risk patients. Bile culture-directed therapy plays an important role in antimicrobial treatment.

Factors Associated With Relapse and Treatment of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease in the United Kingdom.

Importance: Longer-term outcomes and risk factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well established. Objective: To investigate longer-term risk of relapse and factors associated with this risk among patients with MOGAD. Design, Setting, and Participants: This large, single-nation, prospective cohort study was conducted among 276 patients with MOGAD at 5 health care centers in the UK. Data from January 1973 to March 2020 were collected from 146 patients at Oxford and its outreach sites, 65 patients at Liverpool, 32 patients at a children's hospital in Birmingham, 22 patients at a children's hospital in London, and 11 patients at Cardiff, Wales. Data were analyzed from April through July 2020. Main Outcomes and Measures: Risk of relapse and annualized relapse rate were evaluated according to different baseline features, including onset age, onset phenotype, and incident vs nonincident group, with the incident group defined as patients diagnosed with antibodies against myelin oligodendrocyte glycoprotein before a second attack. Time to next relapse among patients experiencing relapse was measured and compared between the maintenance therapy subgroup and each first-line treatment group. The no-treatment group was defined as the off-treatment phase among patients who were relapsing, which could occur between any attack or between the last attack and last follow-up. Results: Among 276 patients with MOGAD, 183 patients were identified as being part of the incident group. There were no differences in mean (SD) onset age between total and incident groups (26.4 [17.6] years vs 28.2 [18.1] years), and female patients were predominant in both groups (166 [60.1%] female patients vs 106 [57.9%] female patients). The most common presentation overall was optic neuritis (ON) (119 patients among 275 patients with presentation data [43.3%]), while acute disseminated encephalomyelitis (ADEM), brain, or brainstem onset was predominant among 69 patients aged younger than 12 years (47 patients [68.1%]), including 41 patients with ADEM (59.4%). In the incident group, the 8-year risk of relapse was 36.3% (95% CI, 27.1%-47.5%). ON at onset was associated with increased risk of relapse compared with transverse myelitis at onset (hazard ratio [HR], 2.66; 95% CI, 1.01-6.98; P = .047), but there was no statistically significant difference with adjustment for a follow-on course of corticosteroids. Any TM at onset (ie, alone or in combination with other presentations [ie, ON or ADEM, brain, or brain stem]) was associated with decreased risk of relapse compared with no TM (HR, 0.41; 95% CI, 0.20-0.88; P = .01). Young adult age (ie, ages >18-40 years) was associated with increased risk of relapse compared with older adult age (ie, ages >40 years) (HR, 2.71; 95% CI, 1.18-6.19; P = .02). First-line maintenance therapy was associated with decreased risk of relapse when adjusted for covariates (prednisolone: HR, 0.33; 95% CI, 0.12-0.92; P = .03; prednisolone, nonsteroidal immunosuppressant, or combined: HR, 0.51; 95% CI, 0.28-0.92; P = .03) compared with the no-treatment group. Conclusions and Relevance: The findings of this cohort study suggest that onset age and onset phenotype should be considered when assessing subsequent relapse risk and that among patients experiencing relapse, prednisolone, first-line immunosuppression, or a combination of those treatments may be associated with decreased risk of future relapse by approximately 2-fold. These results may contribute to individualized treatment decisions.

Safety and side effect profile of Pfizer-BioNTech COVID-19 vaccination among healthcare workers: A tertiary hospital experience in Singapore

INTRODUCTION@#Vaccination remains a key strategy to living endemically with COVID-19. The Pfizer-BioNTech COVID-19 vaccine was first granted interim authorisation for use in Singapore in December 2020. With overseas studies published about the safety and side effect profiles of mRNA COVID-19 vaccines focusing mainly on non-Asian populations, we described the side effects of Pfizer-BioNTech COVID-19 vaccination experienced by the healthcare workers (HCWs) in a tertiary hospital in Singapore.@*METHODS@#Data were obtained from the Occupational Health Clinic (OHC) at the National University Hospital in Singapore, which monitored staff for any adverse effects within 30 minutes post vaccination on-site and any adverse effects after that. A cross-sectional study among the vaccinated HCWs was conducted using an online survey, which established basic demographics, histories of allergies or atopic disorders, and adverse events encountered after dose 1 and dose 2 of vaccination.@*RESULTS@#No anaphylaxis was reported. Most common symptom was giddiness (32.7%) experienced by HCWs within 30 minutes. Adverse events attended post-vaccination by OHC were generally mild and self-limiting. From the survey, odds of experiencing an adverse event after dose 2 was significantly higher than after the first dose, especially for fever/chills (odds ratio [OR] 22.5). Fever/chills, injection site reactions, headache, aches and pains, and feeling unwell were significantly more common in HCWs below 60 years compared to those ≥60 years. An allergy to food (adjusted OR 2.7) and a history of eczema/sensitive skin (adjusted OR 2.6) were associated with a skin reaction not at injection site.@*CONCLUSION@#The side effects experienced after Pfizer-BioNTech COVID-19 vaccines are generally self-limiting and mild, with no anaphylaxis reported.

Sinus and Anterior Skull Base Surgery during the COVID-19 pandemic: Systematic review, Synthesis and YO-IFOS position.

PurposeThe COVID-19 pandemic has caused significant confusion about healthcare providers and patients pandemic-specific risks related to surgery. The aim of this systematic review is to summarize recommendations for sinus and anterior skull base surgery during the COVID-19 pandemic. MethodsPubMed/MEDLINE, Google Scholar, Scopus and Embase were searched by two independent otolaryngologists from the Young Otolaryngologists of IFOS (YO-IFOS) for studies dealing with sinus and skull base surgery during COVID-19 pandemic. The review also included unpublished guidelines edited by Otolaryngology-Head and Neck Surgery or Neurosurgery societies. Perioperative factors were investigated including surgical indications, preoperative testing of patients, practical management in operating rooms, technical aspects of surgery and postoperative management. The literature review was performed according to PRISMA guidelines. The criteria for considering studies or guidelines for the review were based on the population, intervention, comparison, outcome, timing and setting (PICOTS) framework. Results15 international publications met inclusion criteria. Five references were guidelines from national societies. All guidelines recommended postponing elective surgeries. An algorithm is proposed that classifies endonasal surgical procedures into three groups based on the risk of postponing surgery. Patients COVID-19 status should be preoperatively assessed. Highest level of personal protective equipment (PPE) is recommended, and the use of high-speed powered devices should be avoided. Face-to-face postoperative visits must be limited. ConclusionsSinus and skull base surgeries are high-risk procedures due to potential aerosolization of SARS-CoV-2 virus. Protection of health care workers by decreasing exposure and optimizing use of PPE is essential with sinus and anterior skull base surgery.

Improving perioperative pain management: a preintervention and postintervention study in 7 developing countries.

INTRODUCTION: The burden of untreated postoperative pain is high. OBJECTIVE: This study assessed feasibility of using quality improvement (QI) tools to improve management of perioperative pain in hospitals in multiple developing countries. METHODS: The International Pain Registry and Developing Countries working groups, from the International Association for the Study of Pain (IASP), sponsored the project and PAIN OUT, a QI and research network, coordinated it, and provided the research tools. The IASP published a call about the project on its website. Principal investigators (PIs) were responsible for implementing a preintervention and postintervention study in 1 to 2 surgical wards in their hospitals, and they were free to choose the QI intervention. Trained surveyors used standardized and validated web-based tools for collecting findings about perioperative pain management and patient reported outcomes (PROs). Four processes and PROs, independent of surgery type, assessed effectiveness of the interventions. RESULTS: Forty-three providers responded to the call; 13 applications were selected; and PIs from 8 hospitals, in 14 wards, in 7 countries, completed the study. Interventions focused on teaching providers about pain management. Processes improved in 35% and PROs in 37.5% of wards. CONCLUSIONS: The project proved useful on multiple levels. It offered PIs a framework and tools to perform QI work and findings to present to colleagues and administration. Management practices and PROs improved on some wards. Interpretation of change proved complex, site-dependent, and related to multiple factors. PAIN OUT gained experience coordinating a multicentre, international QI project. The IASP promoted research, education, and QI work.

Proof-of-concept preparation and characterization of dual-drug amorphous nanoparticle complex as fixed-dose combination of poorly soluble drugs.

OBJECTIVES: To carry out a proof-of-concept study on the development of dual-drug amorphous nanoparticle complex (nanoplex in short) as a potential formulation platform for fixed-dose combination (FDC) of poorly-soluble drugs. SIGNIFICANCE: FDC has been proven effective in improving patient compliance for treatment that requires complex multidrug regimen. Currently, there is growing interest to develop FDC of poorly-soluble drugs due to the increased number of drugs exhibiting poor solubility thus low bioavailability. METHODS: The dual-drug nanoplex was prepared by electrostatically-driven co-complexation of drug molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and itraconazole (ITZ) as the model poorly-soluble drugs. RESULTS: We first verified that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their distinct thermal behaviors and dissolution characteristics. Depending on the preparation condition, the dual-drug nanoplex exhibited size and zeta potential of 160-410 nm and -35-50 mV, respectively. The individual drug payloads were readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ nanoplex, however, exhibited diminished CIP supersaturation generation, thus lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ supersaturation level. CONCLUSION: Dual-drug nanoplex was successfully prepared with a high degree of control over its physical characteristics. Nevertheless, whether dual-drug nanoplex always exhibits diminished solubility enhancement compared to its single-drug counterparts needs to be investigated using different poorly-soluble drugs.

Real time near-infrared Raman spectroscopy for the diagnosis of nasopharyngeal cancer.

Near-infrared (NIR) Raman spectroscopy has been investigated as a tool to differentiate nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue in an ex-vivo setting. Recently, we have miniaturized the fiber-optic Raman probe to investigate its utility in real time in-vivo surveillance of NPC patients. A posterior probability model using partial linear square (PLS) mathematical technique was constructed to verify the sensitivity and specificity of Raman spectroscopy in diagnosing NPC from post-irradiated and normal tissue using a diagnostic algorithm from three significant latent variables. NIR-Raman signals of 135 sites were measured from 79 patients with either newly diagnosed NPC (N = 12), post irradiated nasopharynx (N = 37) and normal nasopharynx (N = 30). The mean Raman spectra peaks identified differences at several Raman peaks at 853 cm-1, 940 cm-1, 1078 cm-1, 1335 cm-1, 1554 cm-1, 2885 cm-1 and 2940 cm-1 in the three different nasopharyngeal conditions. The sensitivity and specificity of distinguishing Raman signatures among normal nasopharynx versus NPC and post-irradiated nasopharynx versus NPC were 91% and 95%; and 77% and 96% respectively. Real time near-infrared Raman spectroscopy has a high specificity in distinguishing malignant from normal nasopharyngeal tissue in vivo, and may be investigated as a novel non-invasive surveillance tool in patients with nasopharyngeal cancer.

Minimally invasive carcinosarcoma ex pleomorphic adenoma: A case report and literature review with cytohistological correlation.

BACKGROUND: Carcinosarcoma of the salivary glands is a rare neoplasm, and the minimally invasive form constitutes a subgroup with a more favorable prognosis. The cytomorphologic features of this neoplasm can be appreciated on fine-needle aspiration biopsy. METHODS AND RESULTS: We present a patient with a minimally invasive carcinosarcoma ex non-recurrent pleomorphic adenoma (Ca ex PA) who underwent initial fine-needle aspiration biopsy followed by surgical resection. The tumor was composed predominantly of a light microscopic pleomorphic high-grade sarcoma exhibiting partial myoepithelial immunohistochemical features, with a minor component of in situ and invasive salivary duct carcinoma (10%). A limited area with features of a hyalinized pleomorphic adenoma was identified. CONCLUSION: This is the third case report of the cytological features of Ca ex PA of the salivary gland, with histologic correlation. It further illustrates the oncogenic relationship between epithelial and myoepithelial elements in the early stages of carcinosarcomatous transformation. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2483-E2489, 2016.

Strategies in fed-batch cultivation on the production performance of Lactobacillus salivarius I 24 viable cells.

The potential use of fed-batch cultivation (FBC) for improvement of the production of Lactobacillus salivarius I 24 biomass for subsequent use as probiotics was studied using a 2-L stirredtank bioreactor. Three different constant feeding rates (0.1, 0.05, and 0.033 L/h) were applied in FBCs and their effect on carbon metabolism was evaluated. The carbon flux for cell built-up with reduction in lactic acid synthesis was observed in the fed-batch as compared to the batch cultivation mode. The viable cell number obtained in the constant FBC (CFBC) operated at a feeding rate of 0.05 L/h was 8 times higher (10.7×1010 CFU/mL) than that recorded in the batch cultivation. This gave the viable cell yield based on glucose consumed for CFBC of 26 times higher (11.3×1012 CFU/gGlucose) than the batch cultivation. This study demonstrated CFBC, which is simple with minimal use of process control equipment, has an industrial potential for improvement of probiotic production.

Potential natural sensitizers extracted from the skin of Canarium odontophyllum fruits for dye-sensitized solar cells.

Possibility of use of dye extract from skin samples of a seasonal, indigenous fruit from Borneo, namely Canarium odontophyllum, in dye sensitized solar cells (DSSCs) are explored. Three main groups of flavonoid pigments are detected and these pigments exhibit different UV-vis absorption properties, and hence showing different light harvesting capabilities. When applied in DSSCs. The detected pigment constituents of the extract consist of aurone (maritimein), anthocyanidin (pelargonidin) and anthocyanidin (cyanidin derivatives). When tested in DSSC, the highest conversion efficiency of 1.43% is exhibited by cyanidin derivatives, and this is followed by conversion efficiencies of 0.51% and 0.79% for aurone and pelargonidin, respectively. It is shown that individual pigments, like cyanidin derivatives and pelargonidin, exhibit higher power conversion efficiency when compared to that of C.odontophyllum skin pigment mixture (with a conversion efficiency of only 0.68%). The results indicate a possibility of masking effects of the pigments when used as a mixture. The acidification of C.odontophyllum skin pigments with concentrated hydrochloric acid improves the conversion efficiency of the mixture from 0.68% to 0.99%. The discussion in this paper will draw data and observations from the variation in absorption and adsorption properties, the HOMO-LUMO levels, the energy band gaps and the functional group compositions of the detected flavonoids.

The prevalence of fatigue and associated health and safety risk factors among taxi drivers in Singapore

<p><b>INTRODUCTION</b>Driver fatigue is one of the biggest health and safety concerns within the road transport sector. This study aimed to find out the prevalence of fatigue among taxi drivers in Singapore, to better understand the general working and health conditions of this group of people and to determine the risk factors associated with fatigued driving.</p><p><b>METHODS</b>A total of 340 taxi drivers were randomly selected for participation in this self-administered questionnaire survey, with height and weight measurements. The response rate was 68.2%. The survey consisted of four main categories: personal particulars; social habits; work patterns and sleep profile; and Epworth Sleepiness Scale, which was used to estimate the level of daytime sleepiness and fatigue. Multiple logistic regression analysis was used to estimate the adjusted odd ratios and 95% confidence intervals associated with the risk factors related to fatigue among the taxi drivers.</p><p><b>RESULTS</b>A high proportion of the taxi drivers were obese and had self-reported hypertension, diabetes mellitus and high cholesterol. Driver fatigue was associated with very poor/poor self-rating of the quality of sleep, having an additional part-time job, drinking three or more caffeinated drinks daily, and driving more than 10 hours a day.</p><p><b>CONCLUSION</b>We hope that the findings of the present study will improve the awareness regarding the work and health conditions of taxi drivers, and contribute toward the effort to achieve a healthier workforce. A lower prevalence of fatigued driving will lead to lower risks of road traffic accidents, decreased economic loss, increased productivity, and safer roads for all.</p>

Extensive Necrotizing Fasciitis after Fat Grafting for Bilateral Breast Augmentation: Recommended Approach and Management

No abstract available.

TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR+ head and neck cancer cells.

Toll-like receptor 3 (TLR3) agonists have been extensively used as adjuvants for anticancer vaccines. However, their immunostimulatory effects and precise mechanisms of action in the presence of antineoplastic monoclonal antibodies (mAbs) have not yet been evaluated. We investigated the effect of TLR3 agonists on cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against head and neck cancer (HNC) cells, as well as on dendritic cell (DC) maturation and cross-priming of epidermal growth factor receptor (EGFR)-specific CD8+ T cells. The cytotoxic activity of peripheral blood mononuclear cells (PBMCs) or isolated natural killer (NK) cells expressing polymorphic variants (at codon 158) of the Fcγ receptor IIIa (FcγIIIa) was determined in 51Cr release assays upon incubation with the TLR3 agonist poly-ICLC. NK cell stimulation was measured based on activation and degranulation markers, while DC maturation in the presence of poly-ICLC was assessed using flow cytometry. The DC-mediated cross priming of EGFR-specific CD8+ T cells was monitored upon in vitro stimulation with tetramer-based flow cytometry. TLR3-stimulated, unfractionated PBMCs from HNC patients mediated robust cetuximab-dependent ADCC, which was abrogated by NK-cell depletion. The cytolytic activity of TLR3-stimulated NK cells differed among cells expressing different polymorphic variants of FcγRIIIa, and NK cells exposed to both poly-ICLC and cetuximab expressed higher levels of CD107a and granzyme B than their counterparts exposed to either stimulus alone. Poly-ICLC plus cetuximab also induced a robust upregulation of CD80, CD83 and CD86 on the surface of DCs, a process that was partially NK-cell dependent. Furthermore, DCs matured in these conditions exhibited improved cross-priming abilities, resulting in higher numbers of EGFR-specific CD8+ T cells. These findings suggest that TLR3 agonists may provide a convenient means to improve the efficacy of mAb-based anticancer regimens.

The effects of prosocial video games on prosocial behaviors: international evidence from correlational, longitudinal, and experimental studies.

Although dozens of studies have documented a relationship between violent video games and aggressive behaviors, very little attention has been paid to potential effects of prosocial games. Theoretically, games in which game characters help and support each other in nonviolent ways should increase both short-term and long-term prosocial behaviors. We report three studies conducted in three countries with three age groups to test this hypothesis. In the correlational study, Singaporean middle-school students who played more prosocial games behaved more prosocially. In the two longitudinal samples of Japanese children and adolescents, prosocial game play predicted later increases in prosocial behavior. In the experimental study, U.S. undergraduates randomly assigned to play prosocial games behaved more prosocially toward another student. These similar results across different methodologies, ages, and cultures provide robust evidence of a prosocial game content effect, and they provide support for the General Learning Model.

Pseudocyst of the auricle: a histologic perspective.

OBJECTIVE: The aim of the study is to describe the histologic spectrum in the pseudocyst of the auricle and to identify any consistent histologic features of this condition. STUDY DESIGN: A prospective study was performed in which the tissue specimen from patients with pseudocyst of the auricle treated at the Department of Otolaryngology, Singapore General Hospital during a 1-year period was sent for histology. METHODS: Consecutive patients with pseudocyst of the auricle who were treated had their tissue specimen sent for histology. These specimens were independently reviewed by one consultant pathologist. RESULTS: All 16 specimens revealed an intracartilaginous cyst devoid of epithelial lining. Interestingly, there were consistent perivascular mononuclear infiltrates of lymphocytes evident in the connective tissue layer just superficial to the anterior segment of the cartilage. CONCLUSION: Pseudocyst of the auricle is a benign condition predominantly affecting young Asian males. Histology characteristically reveals an intracartilaginous cyst devoid of epithelial lining, and there are no pathognomonic features. We postulate that an inflammatory response is crucial to the development of this condition on the basis of a consistent perivascular inflammatory response seen in all our specimens.