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Background: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy., Methods: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks., Results: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%)., Conclusion: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel. Concentrations of HA and o-/m-/p-MHAs were normalized to those of creatinine and used to analyze urine samples of 160 operating room (OR) healthcare personnel, including administrative staff, surgical nurses, nurse anesthetists, and surgeons. The results showed that the five analytes could be accurately separated and exhibited good linearity (r > 0.9992). The rate of recovery was between 86% and 106%, and the relative standard deviation was less than 5%. Urine from administrative staff presented the highest median concentration of hippuric acid (0.25 g/g creatinine); this was significantly higher than that found in the urine of surgeons (0.15 g/g). The concentrations of urinary o-/m-/p-MHAs in surgical nurses were higher than those in administrative staff, nurse anesthetists, and surgeons. Furthermore, the type, sex, and age of healthcare personnel were associated with changes in urine HA and o-/m-/p-MHA concentrations. Healthcare personnel should be aware of the risk of exposure to surgical smoke., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The composition and concentration distribution of volatile organic compounds (VOCs) in surgical smoke had seldomly been reported. This study aimed to investigate the profile of VOCs and their concentration in surgical smoke from breast surgery during electrocautery in different tissues, electrosurgical units, and electrocautery powers., Methods: Thirty-eight surgical smoke samples from 23 patients performed breast surgery were collected using evacuated stainless steel canisters. The concentrations of 87 VOCs in surgical smoke samples were analyzed by gas chromatography-mass spectrometry. The human tissues, electrosurgical units, and electrocautery power were recorded., Results: The median level of total VOCs concentrations in surgical smoke samples from mammary glands (total VOCs: 9953.5 ppb; benzene: 222.7 ppb; 1,3-butadiene: 856.2 ppb; vinyl chloride: 3.1 ppb) using conventional electrosurgical knives were significantly higher than that from other tissues (total VOCs: 365.7-4266.8 ppb, P < 0.05; benzene: 26.4-112 ppb, P < 0.05; 1,3-butadiene: 15.6-384 ppb, P < 0.05; vinyl chloride: 0.6-1.8 ppb, P < 0.05) using different electrosurgical units. A high methanol concentration was found in surgical smoke generated during breast surgery (641.4-4452.5 ppb) using different electrosurgical units. An electrocautery power of ≥ 27.5 watts used for skin tissues produced a higher VOCs concentration (2905.8 ppb)., Conclusions: The surgical smoke samples collected from mammary glands using conventional electrosurgical knives had high VOCs concentrations. The carcinogens (including benzene, 1,3-butadiene, and vinyl chloride) and methanol were found in the surgical smoke samples from different electrosurgical units. The type of electrosurgical unit and electrocautery power used affected VOCs concentrations in surgical smoke., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Alginate hydrogels have been investigated for a broad variety of medical applications. The ability to assemble hydrogels at neutral pH and mild temperatures makes alginate a popular choice for the encapsulation and delivery of cells and proteins. Alginate has been studied extensively for the delivery of islets as a treatment for type 1 diabetes. However, poor stability of the encapsulation systems after implantation remains a challenge. In this paper, alginate was modified with 2-aminoethyl methacrylate hydrochloride (AEMA) to introduce groups that can be photoactivated to generate covalent bonds. This enabled formation of dual crosslinked structure upon exposure to ultraviolet light following initial ionic crosslinking into bead structures. The degree of methacrylation was varied and in vitro stability, long term swelling, and cell viability examined. At low levels of the methacrylation, the beads could be formed by first ionic crosslinks followed by exposure to ultraviolet light to generate covalent bonds. The methacrylated alginate resulted in more stable beads and cells were viable following encapsulation. Alginate microbeads, ionic (unmodified) and dual crosslinked, were implanted into a rat omentum pouch model. Implantation was performed with a local injection of 100 µl of 50 µg/ml of Lipopolysaccharide (LPS) to stimulate a robust inflammatory challenge in vivo. Implants were retrieved at 1 and 3 weeks for analysis. The unmodified alginate microbeads had all failed by week 1, whereas the dual-crosslinked alginate microbeads remained stable up through 3 weeks. The modified alginate microbeads may provide a more stable alternative to current alginate-based systems for cell encapsulation., Statement of Significance: Alginate, a naturally occurring polysaccharide, has been used for cell encapsulation to prevent graft rejection of cell transplants for people with type I diabetes. Although some success has been observed in clinical trials, the lack of reproducibility and failure to reach insulin dependence for longer periods of time indicates the need for improvements in the procedure. A major requirement for the long-term function of alginate encapsulated cells is the mechanical stability of microcapsules. Insufficient mechanical integrity of the capsules can lead to immunological reactions in the recipients. In this work, alginate was modified to allow photoactivatable groups in order to allow formation of covalent crosslinks in addition to ionic crosslinking. The dual crosslinking design prevents capsule breakdown following implantation in vivo., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hydrogels are considered to be attractive cell-matrix for chondrocytes due to their similarity in properties to the natural cartilage. However, the formation of chondrocyte cell clusters in hydrogels has been mostly limited to naturally-derived or relatively fast degrading materials. In this study, a series of diblock copolymer poly(ethylene glycol)-poly(alanine) (mPEG-PA) was synthesized and investigated as injectable biomimic hydrogels for the culturing of chondrocytes. Depending on the poly(alanine) chain length, afforded hydrogels exhibited variable mechanical property and microarchitecture due to difference in secondary structure arrangement. After 21days of culture, cell clusters were observed in all hydrogels with longer PA chains and these hydrogels supported more homogenous and established clustering as well as significantly higher glycosaminoglycan and collagen deposition. Interestingly, scanning electron microscopy revealed a distinct micron range fibrillar-like microarchitecture that may be responsible for maintaining chondrocyte phenotype and matrix production. In addition, micrographs revealed the presence of collagen fibrils and an extensive extracellular matrix network. Therefore, it is reasonable to conclude that mPEG-PA hydrogels possess the desirable properties for chondrocyte cluster formation and serve as potential candidate in cartilage tissue engineering., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Using a case study to discuss the effects of traditional Chinese medicine (TCM) treatments on Type 1 diabetes mellitus., Clinical Features: A 4-year-old girl with sudden polyuria and nocturia (fasting plasma glucose level: 270mg/dL) was diagnosed with type 1 diabetes. Although multiple daily insulin injections were applied, her plasma glucose levels were still unstable. Therefore, she received a complementary TCM therapy by taking modified Liu-Wei-Di-Huang-Wan (3.0g/day; three times daily) for 3 months. After the treatments, her plasma glucose levels appeared to be more stable. HbA 1c 6.5% and insulin injections were reduced to only once a day., Conclusions: The results suggest that complementary TCM therapy has the ability to assist some patients with type 1 diabetes mellitus in controlling their plasma glucose levels., (Copyright © 2016. Published by Elsevier Ltd.)

Introduction: Little is known about the costs of treating burn patients after a mass casualty event. A devastating Color Dust explosion that injured 499 patients occurred on June 27, 2015 in Taiwan. This study was performed to investigate the economic effects of treating burn patients at a single medical center after an explosion disaster., Methods: A detailed retrospective analysis on 48 patient expense records at Chang Gung Memorial Hospital after the Color Dust explosion was performed. Data were collected during the acute treatment period between June 27, 2015 and September 30, 2015. The distribution of cost drivers for the entire patient cohort (n=48), patients with a percent total body surface area burn (%TBSA)≥50 (n=20), and those with %TBSA <50 (n=28) were analyzed., Results: The total cost of 48 burn patients over the acute 3-month time period was $2,440,688, with a mean cost per patient of $50,848 ±36,438. Inpatient ward fees (30%), therapeutic treatment fees (22%), and medication fees (11%) were found to be the three highest cost drivers. The 20 patients with a %TBSA ≥50 consumed $1,559,300 (63.8%) of the total expenses, at an average cost of $77,965±34,226 per patient. The 28 patients with a %TBSA <50 consumed $881,387 (36.1%) of care expenses, at an average cost of $31,478±23,518 per patient., Conclusions: In response to this mass casualty event, inpatient ward fees represented the largest expense. Hospitals can reduce this fee by ensuring wound dressing and skin substitute materials are regionally stocked and accessible. Medication fees may be higher than expected when treating a mass burn cohort. In preparation for a future event, hospitals should anticipate patients with a %TBSA≥50 will contribute the majority of inpatient expenses., Competing Interests: Statement Research reported in this publication was supported in part by grants from the University of Michigan Medical School Student Biomedical Research Program (to John-Michael Muller), and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number 2 K24-AR053120-06 (to Dr. Kevin C. Chung). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors listed in this manuscript report no conflicts of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Pluronic F-127 (PF127) is a thermosensitive polymer that has been widely recognized as a potential candidate for various bio-applications. However, in hydrogel form, its rapid disintegration and inhospitality toward cells have significantly limited its usage. As a means to increase the integrity and cell compatibility of a PF127 hydrogel, we propose the introduction of stabilizing secondary structures to the gel network by the addition of secondary structure-forming oligo-alanine and oligo-phenylalanine. Results indicate that increasing the oligo(peptides) attached to PF127 led to a significant decrease in the gelation concentration and temperature. A selected oligo(peptide)-modified PF127 was capable of forming a stable hydrogel network at 5% and suffered only 20% weight loss after 7days of incubation in media. Scanning electron microscopy (SEM) revealed comparably more interconnected morphology in modified hydrogels which may be attributed to the presence of secondary structures, as verified by circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. Nuclear magnetic resonance (NMR) provided insights into the extensive interactions at the micelle core, which is the key to altered gelation behavior. Furthermore, modified hydrogels maintained structural integrity within culturing media and supported the proliferation of encapsulated chondrocytes. In addition, in vivo residence time was extended to well beyond 2weeks after oligo(peptide) modification, thereby broadening the application scope of the PF127 hydrogel to encompass long-term drug delivery and cell culturing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Wound healing and skin tissue engineering are mediated, in part, by interactions between cells and the extracellular matrix (ECM). A subset of the ECM, basement membranes (BM), plays a vital role in regulating proper skin healing and function., Methods: ECM-rich, tissue-specific hydrogels were extracted and assembled from dermis samples. These hydrogels contain BM proteins vital to skin regeneration, including laminin β3, collagen IV, and collagen VII. The extracts could be assembled to form hydrogels by either temperature or pH mechanism, with the mechanical properties and structure varying with the mechanism of assembly. A wound healing model was developed to investigate the ability of these hydrogels to enhance healing with a single application in vivo., Results: The pH, but not temperature gels were easily applied to the wounds. There were no signs of increased inflammation due to the application of the hydrogels. The width of granulation tissue at the first week was reduced (p = 0.064) relative to controls with the application of hydrogel. There were no changes in wound closure rates or vessel density., Conclusions: Dermis-derived hydrogels contain BM proteins important for skin regeneration. They can be easily applied, but their poor mechanical strength and rapid degradation may hinder their biological effects.

Objective: To identify the risk factors for postoperative morbidities in elderly patients (≧65 years old) who underwent head and neck tumor ablation followed by immediate free tissue transfer., Methods: We performed a retrospective analysis of 1012 patients who underwent free tissue transfer after head and neck cancer ablation between 2007 and 2010. A total of 167 patients aged 65 and older were identified. These patients were divided into two age-related subgroups: patients aged between 65 and 70 years in one cohort and patients older than 70 years in the second cohort. The demographic and operative variables as well as postoperative medical and surgical morbidities were analyzed., Results: The older group had significantly prolonged ICU stay (p = 0.014) and hospital stay (p = 0.039). The same group also had higher rates of intraoperative blood transfusion ≧2 units (p = 0.019), unplanned reintubation (p < 0.001), medical (p = 0.004), and surgical (p < 0.001) complications. The intraoperative blood loss of >220 mL was a significant predictive factor for postoperative medical morbidities (odds ratio [OR] 2.25; 95% confidence interval [CI], 1.01-5.03; p = 0.048). The age of >70 years was an independent risk factor for postoperative medical and surgical morbidity (OR [95% CI]: 4.08 [1.67-9.99] and 3.48 [1.56-7.78], p = 0.002, respectively)., Conclusions: Age over 70 years and intraoperative blood loss of >220 mL are significant risk factors for predicting postoperative morbidity, and a thorough pre-treatment evaluation and care for elderly patients are required., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Osteoporotic patients with existing fractures are at substantially higher risk of subsequent fractures than those free of fractures. Given the lack of head-to-head comparison trials, indirect comparison of various antiosteoporosis treatments may be an alternative way to develop a preliminary idea. The objective of this study is to conduct a systematic review of antiosteoporosis treatment clinical trials that have investigated on patients with existing fractures. All the results of randomized placebo-controlled trials of the available antiosteoporosis treatments, including bisphosphonates, selective estrogen receptor modulators, calcitonin, strontium ranelate, and agents derived from parathyroid hormone, on patients with existing fractures were summarized. All the antiosteoporotic agents had significant efficacy in increasing lumbar spine bone mineral density and reduction in the occurrence of any new vertebral fractures. All interventions provided gains in quality-adjusted life-years compared with patients without treatment. The results from an indirect comparison must be interpreted with caution due to heterogeneous study design, discrepancies of disease severity at baseline, and differences in analytical methodologies. The devastating complications subsequent to osteoporotic fractures create medical and financial burdens; therefore, treatment of patients with osteoporotic fractures should be positioned in the top priority in the utilization of medical resources., (Copyright © 2012. Published by Elsevier B.V.)

Background: Oral submucous fibrosis is a collagen disorder affecting the submucosal layer and can severely limit mouth opening. The use of bilateral forearm flaps to fill buccal defects following trismus release has proven to be effective and reliable. However, it requires the sacrifice of radial arteries from both forearms. We have developed a technique that allows for the harvest of two independent flaps from a single forearm donor site., Methods: Two separate flaps are designed on the same radial artery and concomitant vein pedicle. The distal flap is marked in the standard fashion and the proximal skin paddle is designed in the middle third of the forearm, based on septocutaneous branches of the radial artery. The two flaps are elevated and subsequently divided into two independent free flaps. Between June 2004 and June 2007, a total of 16 flaps were harvested from eight donor sites for buccal mucosa defects following trismus release. Improvements in mouth opening and buccal pliancy were evaluated by comparing preoperative and postoperative inter-incisal distance (IID) and maximal mouth capacity., Results: All flaps survived completely, and all donor sites were closed primarily, except for one. The mean flap size was 6.6x2.6cm (range: 6x2.5cm-7x3cm), mean pedicle length was 5.7cm, mean ischaemia time was 46min and mean total operating time was 8h 45min. At an average of 19.8 months follow-up, the inter-incisal distance averaged 29.13mm, an increase of 20.88mm compared with the preoperative measurement. The maximal mouth capacity averaged 55.63cc, an increase of 9.38cc compared with the preoperative measurement., Conclusion: Two independent small flaps can be harvested safely from one radial forearm donor site. This approach is a useful option for reconstruction of bilateral buccal defects, particularly following submucous fibrosis release. The donor-site morbidity is minimal and limited to one forearm., (Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Oral submucous fibrosis causes health-related and social problems for affected patients. Free flap reconstruction has proved effective for maintaining mouth opening after release of fibrosis. Two independent free flaps from separate donor sites, such as bilateral forearm flaps or bilateral anterolateral thigh (ALT) flaps, were traditionally required for reconstruction. The former option sacrifices one of the two major arteries in the forearm. Both options are time consuming and required two donor sites. To eliminate these disadvantages, we developed a technical modification that allows harvesting of two independent flaps from one ALT thigh based on one descending branch of the lateral circumflex femoral artery (d-LCFA). Eighteen flaps from nine donor sites were harvested for post-release reconstruction of oral submucous fibrosis. Mean flap size was 4.1 x 7.5 cm, mean pedicle length was 7.6 cm, mean ischaemia time was 104 min and mean total operation time was 13 h and 19 min. All donor sites were closed primarily, with one exception. One flap failed and was replaced with a contralateral ALT flap. One patient developed a wound infection and another developed a seroma at the recipient site. Four flaps required secondary de-bulking in three patients. The improvement in mouth opening was evaluated by inter-incisor distance (IID): mean preoperative IID was 9.6mm (range: 0-20mm), mean follow-up time was 16.2 months (range: 10-33 months); mean postoperative IID was 23.8mm and mean improvement in IID was 15.3mm (range: 10-27 mm). In conclusion, two independent flaps can be harvested from d-LCFA of the same thigh, instead of from both thighs, to reconstruct bilateral buccal defects after release of submucous fibrosis and/or contracture., ((c) 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Several authors have cited liver cirrhosis as a risk factor for surgery but no study performed statistical correlation between flap outcome and severity of liver cirrhosis in patients with head and neck cancer. We performed a retrospective analysis of 3108 patients who underwent free tissue transfer after head and neck cancer ablation between January 2000 and December 2008. Liver cirrhosis was identified in 62 patients. Forty-two patients (67.7%) were classified as having Child's class A cirrhosis, seventeen (27.4%) as having class B, and three (4.9%) as having class C cirrhosis. The overall complete flap survival rate was 90.3% (56/62). The flap-related complications of patients with Child's class A, B, and C were 38.1% (16/42), 47.1% (8/17), and 100% (3/3), respectively and showed no significant difference between these three groups (p=0.2758). The rate of postoperative neck hematoma was 14.5%; the risk of postoperative neck hematoma was significantly higher in patients with more advanced liver cirrhosis (p=0.0003). The recipient-site complications of patients with Child's class A cirrhosis, Child's class B, and Child's class C cirrhosis were 35.7%, 41.1%, and 66.6%, respectively, with no significant difference among the three groups. The statistical analysis demonstrated that diabetes mellitus is significantly associated with a negative prognosis for free flap reconstruction (p=0.0364). The flap survival rate and patency of microvascular anastomosis have no association with liver cirrhosis. To achieve a superior surgical outcome, preoperative optimization and a multidisciplinary team responsible for the evaluation and treatment of head and neck cancer patients with cirrhosis are necessary.

Study Objective: To compare the difference between laparoscopic uterine vessel occlusion (LUVO) and ultra-minilaparotomy (UMLT) uterine vessel occlusion (UVO) in the management of symptomatic uterine myomas with 2-year follow-up., Design: Observational study (Canadian Task Force classification II-3)., Setting: University-associated hospital., Patients: Ninety-one patients with symptomatic leiomyoma., Interventions: Uterine vessel occlusion via laparoscopy (n=51) or UMLT access (n=40)., Measurements and Main Results: Outcome was determined by comparing operative time, complications, successful operation rate, postoperative pain, time to resumption of a regular diet, time to return to work, 2-year symptom control, relapse of symptoms, and repeat intervention between both groups. There were no statistical differences in 2-year symptom control, relapse of symptoms, repeat intervention, surgical complications, and successful operation rate between the 2 groups; however, LUVO yielded shorter operative time, less operative pain, shorter time to resumption of a regular diet, and earlier return to work, compared with UMLT-UVO., Conclusion: If UVO is chosen for management of symptomatic uterine myoma, both the LUVO and UMLT are acceptable options, with similar therapeutic outcomes; however, LUVO might yield more rapid postoperative recovery.

Objective: To determine the acceptability and effectiveness of a gonadotropin-releasing hormone (GnRH) agonist for the treatment of perimenopausal women with symptomatic uterine myomas., Materials and Methods: The participants included 43 women with symptomatic myomas who wished to retain their uteri. All the women were older than 45 years old, agreed to use the GnRH agonist for menopause induction, and were without any underlying malignancy. They were treated with six courses of GnRH agonist between 2004 and 2005. The definition of re-intervention included: (1) surgical intervention, such as hysterectomy, myomectomy or laparoscopic uterine vessel occlusion, or (2) modification of GnRH agonist use. Modification of GnRH agonist use included either failure to complete a 6-month GnRH agonist treatment course, or re-use of GnRH agonist with/without interruption of continuity. Failure was defined as women who underwent surgical intervention or failed to complete the 6-month GnRH agonist treatment. Evaluations were performed every 6 months, for up to 2 years., Results: Re-intervention rates were 14.0% (n = 6), 23.3% (n = 10) and 32.6% (n = 14), and failure rates were 7.0% (n = 3), 11.6% (n = 5) and 16.3% (n = 7), at the end of the 6-, 12- and 24-month follow-up periods, respectively. Three patients failed to complete the 6-month GnRH agonist treatment, and four received surgical interventions., Conclusion: More than 80% of women in this study benefited from the use of GnRH agonist to produce menopause, suggesting that this can be an alternative choice for managing perimenopausal women with symptomatic uterine myomas.

Ascites is a pathologic accumulation of fluid within the peritoneal cavity, and usually develops as a result of liver disease, congestive heart failure or nephrotic syndrome. Ascites is also a common manifestation of some gynecologic diseases. It is important that health care workers consider gynecologic problems among the potential differential diagnoses in patients presenting with ascites. Various kinds of ovarian diseases, such as epithelial ovarian cancer, benign ovarian fibroma, stromal hyperplasia, ovarian hyperstimulation syndrome, primary peritoneal serous carcinoma, endometriosis and peritoneal tuberculosis, should be kept in mind when women are found to have ascites.

Although many large series of free tissue transfers for head and neck reconstruction have been reported in adults, there are few studies in paediatric patients. Seventy-three free tissue transfers for reconstruction of various defects of the head and neck were performed in 72 paediatric patients between January 1990 and September 2002, at our centre. The average age at the time of reconstruction was 11.8 years (range: 2 to 17 years). Thirty-eight patients were girls and 34 were boys. There were 19 tumour resection defects, 18 congenital oro-nasal fistula defects (cleft palate), 11 posttraumatic defects, nine corrosive pharyngo-oesophageal injuries, eight burn contractures, six hemifacial atrophies and microsomia, and one facial paralysis. Thirty-nine fasciocutaneous flaps, 16 osteoseptocutaneous flaps, 10 muscle or myocutaneous flaps, and eight jejunal flaps were transferred. The mean operative time was 8 h 20 min. All flaps survived, except one partial necrosis, with 98.6% success rate. Five patients (6.8%) required re-exploration. There were two venous and three arterial thromboses. All five flaps were successfully salvaged. The average hospital stay was 18 days. This study confirmed free tissue transfer as a safe, reliable, cost- and time-effective method for the reconstruction of various head and neck defects in children.

The link between hormones and breast cancer growth and development has been recognized for more than a century. Estrogen stimulates the proliferation of breast epithelial cells, and both endogenous and exogenous estrogens have been implicated in the pathogenesis of breast cancer. Classically, estrogen action at target sites around the body is mediated through related but distinct estrogen receptors (ERs), designated ERalpha and ERbeta, to alter gene expression. This accumulating understanding of the mechanism of action of estrogen led ultimately to the design of antiestrogenic agents that work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs). Tamoxifen, a SERM, emerged as the first antiestrogenic agent that is clinically applicable to breast cancer. Tamoxifen became the "gold standard" and established the principles of tumor targeting and identified the appropriate treatment strategy to aid survivorship in breast cancer patients, with enhancement of disease-free survival and a 50% decrease in recurrences observed in ER-positive patients 15 years after diagnosis. However, because of the many adverse events in the use of tamoxifen, some of which have contributed to significant morbidity and mortality, drug modification which has resulted in fewer incidences of adverse events without compromising the therapeutic effect for breast cancer prevention may face an easier road to acceptance. Raloxifene may be a better alternative, since evidence from large clinical trials showed that raloxifene not only decreases the incidence of osteoporosis and related fractures, but also offers benefits for breast cancer prevention. The results from the Study of Tamoxifen and Raloxifene (STAR) trial showed the superiority of raloxifene over tamoxifen, not only for the equal efficacy in the prevention of invasive breast cancer but also for the fewer serious adverse events. Taken together, without other competition so far, raloxifene is recommended for postmenopausal women with osteoporosis who also need breast cancer prevention.

The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor alpha-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cell-mediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT) has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT) might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT) sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT can be used with symptomatic menopausal women, but is worthy of further evaluation because we found the following potential benefits, including (i) low-dose oral EPT appears to be effective for the alleviation of climacteric symptoms; (ii) it has a good tolerability profile with a low incidence of the most common and problematic side effects, such as breast tenderness and an increased mammographic density. Altogether, when compared with the standard dose HT, physicians may prefer to use low-dose HT initially in managing the climacteric symptoms of postmenopausal women. Time will prove.

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, the prolonged use of either single estrogen therapy (ET) or a combination therapy of estrogen and progestogen (EPT) might be associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention and/or treatment of menopause, having associated morbidities but no unwanted effects, are of primary interest in clinical practice. Tibolone (Livial; NV Organon, Oss, The Netherlands) is structurally related to 19-nortestosterone derivatives and is a new postmenopausal regimen with a unique pharmacological profile, licensed for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women. Tibolone exhibits weak estrogenic, progestogenic, and androgenic activities, which in theory might influence the breast. The effect of tibolone on breast tissue, however, is obscure. The purpose of this study was to assess the effects of tibolone on breast safety, and the collected data include preclinical models, clinical observation, and epidemiologic study. Although in vitro studies showed conflicting results (with the majority being favorable effects) regarding the effects of tibolone on breast cells, in vivo studies showed favorable effects of tibolone on the breast in animal models. Similarly, an epidemiologic study indicated an increased risk of breast cancer when tibolone was used to manage climacteric symptoms of postmenopausal women, but accumulated data obtained from radiologic studies (mammography) showed a possible protective effect of tibolone on the breast. Taken together, we conclude that tibolone, if not superior to conventional HT, may be more acceptable to clinicians as a therapeutic drug option for use with symptomatic menopausal women. Only time will tell whether tibolone will be the preferred option.

Three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T might be a cancer susceptible factor for several cancers. In this study, we genotyped 226 head-and-neck squamous-cell carcinoma (HNSCC) patients and 249 controls to examine the association between three SNPs of the DNMT3B promoter and the associated risk of the development and/or metastasizing tendency of HNSCC for the population of Taiwan. We observed that only the T/T genotype (C46359T) was found to be present in both patient and control groups (100% frequency). The alleles frequency of -283CC, -283CT and -283TT among patients and controls was, respectively, 88.1% versus 84.3%, 11.9% versus 15.3%, and 0% versus 0.4%. The allele -597GG was not found in both groups, whereas the allele frequency of -597TT and -597GT for patients and controls was, respectively, 88.1% versus 85.5%, and 11.9% versus 14.5%. For both DNMT3B SNPs, inter-group comparison of the allele frequency between patients and controls and distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis did not reveal any significant difference. In conclusion, the relative distribution of three DNMT3B SNPs among a Taiwanese population can not be used as a stratification marker to predict either an individual's susceptibility to HNSCC and/or the likelihood of cervical metastasis of HNSCC.

Nipple reconstruction is usually the final stage of breast reconstruction and there are over 50 articles that describe different techniques. The majority of methods use local soft tissue as local flaps but they face the disadvantage of reduction in nipple projection after the initial two months. This is particularly troublesome in Asian females who may have wider nipples with prominent projection but small areola surface area. We developed a method to correct this problem using cartilage graft harvested during the initial breast reconstruction operation and banked beneath the skin flap. Using the modified 'top hat' flap, we found that no excess soft tissue is required to compensate for the reduction. We have used this method in 25 cases of nipple reconstruction and have obtained satisfactory result in projection.

We describe three free jejunal flaps that lost their axial blood supply in the early postoperative period--two flaps on the 7th day and the third on the 17th day. At 7 days, reestablishment of axial blood flow was essential to flap survival, whereas after 17 days, vascularization from the recipient bed was adequate to maintain viability. Based on these observations, a conservative approach to flap salvage for cases with pedicle disruption at 17 days or later is recommended.