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   Table of Contents - Current issue
Coverpage
October-December 2020
Volume 32 | Issue 4
Page Nos. 305-405

Online since Tuesday, September 29, 2020

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REVIEW ARTICLE - BASIC  

The role of transcription factor caudal-related homeobox transcription factor 2 in colorectal cancer p. 305
Chin-Chia Wu, Ta-Wen Hsu, Chia-Chou Yeh, Hsien-Bing Huang
DOI:10.4103/tcmj.tcmj_49_20  
Colorectal cancer (CRC) is one of the most malignant tumors in humans and causes mass mortality. In the age of precise medicine, more and more subtypes of CRC were classified. The caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor which is implicated in differentiation, proliferation, cell-adhesion, and migration. The loss of CDX2 in immunohistochemical stain was reported to be a prognostic factor of colon cancer, but the clinical application remained controversial. Most of the CRCs expressed or over-expressed CDX2. Homeobox genes can display either an oncogenic or a tumor-suppressing activity. CDX2 regulates the developing intestinal epithelium and CRC by different pathways. The complex regulation of CDX2 and its complex targets cause the difficulties of application for CDX2 in the prediction of prognosis. However, CDX2 is a potential biomarker applied in the precise classification of CRC for personalized medicine. This review partially clarifies the role of CDX2 in CRC.
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REVIEW ARTICLES - CLINICAL Top

Role of hypothyroidism and associated pathways in pregnancy and infertility: Clinical insights p. 312
Arun Koyyada, Prabhakar Orsu
DOI:10.4103/tcmj.tcmj_255_19  
Thyroid disorders are the most common endocrine problems in women. In most of the cases, thyroid can lead to infertility or miscarriages. The etiology of infertility is multifactorial with thyroid disorders as the most common presenting factor, hypothyroidism in particular. Infertility in women can lead to emotional and psychological stress. The prevalence of hypothyroidism during pregnancy is estimated to be 0.3%–0.5%. Hypothyroidism and hyperthyroidism can result in menstrual irregularities and anovulatory cycles, thus affecting the fertility. There is a significant high prolactin (PRL) level in infertile women with hypothyroidism when compared to euthyroid patients, indicating the relation between hypothyroidism and hyperprolactinemia. The amount ofthyrotropin releasing hormone (TRH) from the hypothalamus is markedly increased by inhibition of pyroglutamyl peptidase II, the enzyme catalyzing TRH. Theincreased TRH in hypothyroidism causes increased thyroid-stimulating hormone and PRL secretion by pituitary, leading to infertility and galactorrhea. Inrecent years, a neuropeptide called kisspeptin, encoded by Kiss1 gene, a potent stimulus for GnRH secretion, has been recognized, which suggests a future direction of treatment with kisspeptin and benefits the fertility induction among hyperprolactinemic infertile patients. Untreated hypothyroidism during pregnancy can lead to subfertility, fetal deaths, premature deliveries, and abortions. Therefore, women planning for pregnancy and infertile women should be assessed for thyroid hormones and serum PRL.
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Mirtazapine-associated movement disorders: A literature review p. 318
Jamir Pitton Rissardo, Ana Leticia Fornari Caprara
DOI:10.4103/tcmj.tcmj_13_20  
Mirtazapine (MTZ) is an atypical antidepressant approved by the FDA, which mechanism of action involves the antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3 receptors. In this context, the aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of MTZ-associated movement disorders (MDs). Relevant reports of six databases were identified and assessed by two reviewers without language restriction. Fifty-two reports containing 179 cases from 20 countries were assessed. The mean age was 57 year (range, 17–85). The majority of the individuals were female (60%) and of European origin. The mean time from MTZ start to symptom onset was 7.54 days; the time from management to MD improvement was within one week in 82.60% of the individuals. The MDs associated with MTZ were 69 restless legs syndrome (RLS), 35 tremors, 10 akathisia (AKT), 9 periodic limb MD, 6 dystonia, 4 rapid eye movement sleep behavior disorders, 3 dyskinesia, 2 parkinsonism, and 1 tic, and in the group not clearly identified, 18 restlessness, 15 hyperkinesis, and 1 extrapyramidal symptom. In the literature, the majority of the reports lack important information about the neurological examination. The management should be the MTZ withdrawal, except in RLS that other options are possible. In AKT, the MTZ should not be rechallenge, and if available, the prescription of a benzodiazepine may reduce recovery time.
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Drug-drug interactions between direct-acting antivirals and statins in the treatment of chronic hepatitis C p. 331
Meng-Hsuan Kuo, Chih-Wei Tseng, Chi-Hui Lee, Kuo-Chih Tseng
DOI:10.4103/tcmj.tcmj_247_19  
As the first line of treatment for hepatitis C virus (HCV) infection, direct-acting antivirals (DAAs) have greater efficacy and fewer adverse effects than other treatments; however, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, such as statins. HCV patients are mostly in the need for polypharmacy, particularly the comedication of DAAs and cardiovascular drugs such as statins. This poses a risk of pharmacokinetic interactions between the two classes of drugs that may lead to severe myopathy or even rhabdomyolysis. Therefore, evaluating the severity of the DDIs and managing them is important. A multidisciplinary team-based model of care for HCV patients receiving DAAs can review the pharmacology profiles of other drugs for relevant DDIs with the DAAs, before prescription. Such a model can also follow the patients through the therapeutic cycle to make sure that their medical regimen is safe and effective. This article reviews the comedication rate and DDI-prevalence in HCV patients receiving statins along with the DAAs, details the mechanisms involved, gives recommendations for management, and shares our experience with a multidisciplinary team-based care program for the treatment of HCV patients.
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REVIEW ARTICLE - MEDICAL ETHICS Top

The impact of artificial intelligence on human society and bioethics p. 339
Michael Cheng-Tek Tai
DOI:10.4103/tcmj.tcmj_71_20  
Artificial intelligence (AI), known by some as the industrial revolution (IR) 4.0, is going to change not only the way we do things, how we relate to others, but also what we know about ourselves. This article will first examine what AI is, discuss its impact on industrial, social, and economic changes on humankind in the 21st century, and then propose a set of principles for AI bioethics. The IR1.0, the IR of the 18th century, impelled a huge social change without directly complicating human relationships. Modern AI, however, has a tremendous impact on how we do things and also the ways we relate to one another. Facing this challenge, new principles of AI bioethics must be considered and developed to provide guidelines for the AI technology to observe so that the world will be benefited by the progress of this new intelligence.
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ORIGINAL ARTICLE - BASIC RESEARCH Top

Safrole-induced expression of proinflammatory responses is associated with phosphorylation of mitogen-activated protein kinase family and the nuclear factor-κB/inhibitor of κB pathway in macrophages p. 344
Yung-Lun Ni, Huan-Ting Shen, Min-Wei Lee, Kun-Lin Yeh, Chen-Yu Chiang, Yu-Hsiang Kuan
DOI:10.4103/tcmj.tcmj_78_20  
Objective: Safrole, also called shikimol and Sassafras, is the carcinogenic and phenylpropanoid compound extracted from Sassafras tree and anise, betel, and camphor. Moreover, a high concentration of safrole can be occur in the saliva because of betel nut or areca quid chewing which a common habit observed in Southern and Southeastern Asia. Notably, macrophages are crucial phagocytic cells of the immune system. Nonetheless, to date, no evidence has been reported regarding safrole-induced proinflammatory response and the corresponding mechanism in macrophages. Materials and Methods: In the present study, the cytokines expression, NO generation, protein phosphorylation, and expression were assessed by enzyme-linked immunosorbent assay, Griess reagent, and Western blot assay, respectively. Results: In this study, we determined that safrole induces the generation of nitric oxide and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and IL-6 in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, inhibitor of κB (IκB) degradation was caused by safrole in a concentration-dependent manner. In addition, the phosphorylation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) family, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was induced by safrole began to increase at 10 μM and attained a plateau at 100 μM. Conclusion: These results indicated that safrole induces the expression of proinflammatory responses in macrophages through the NF-κB/IκB pathway and its upstream factor, MAPK family phosphorylation.
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ORIGINAL ARTICLES - CLINICAL RESEARCH Top

Magnetic resonance assessment of medial plica syndrome of knee from child to adult with arthroscopic correlation: A single center experience and literature review p. 351
Reddy Ravikanth, Anoop Pilar, Pooja Majumdar
DOI:10.4103/tcmj.tcmj_150_19  
Objective: Synovial plicae are mesenchymal tissue remnants invaginating into the knee joint. Their classification is based on the location as lateral, mediopatellar, suprapatellar, and infrapatellar. Mediopatellar plica is commonly symptomatic. The purpose of this study was to identify magnetic resonance (MR) characteristics of the medial plica and to correlate with arthroscopy for cause confirmation in patients with painful knee. Materials and Methods: The current study was undertaken over a 2-year period between July 2017 and June 2019 in the department of radiology at a tertiary care hospital in India. MR examinations of the knee joint were performed using QUADKNEE coil on a 1.5-T scanner (Signa, General Electric Medical Systems, Milwaukee, WI, USA). The criteria studied were: presence of the plica, interposition into the femoropatellar joint, intraarticular effusion, and fenestrated aspect. Twenty-two knees (20 patients) diagnosed with mediopatellar plica syndrome on MR imaging (MRI), and with no other knee pathology, were treated with arthroscopic division of plicae. Results: Only two (20.0%) of the ten knees in which the plicae had not been divided have shown improvement and six (85.7%) of the seven knees in which plica had been divided (P < 0.05) have shown improvement. Subsequent division of the plicae resulted in improvement in seven of the eight knees (87.5%) (P < 0.01). Patients presented with crepitus in 9% of cases (2 of 22), instability in 13.6% (3 of 22), pseudo-locking in 45.4% (10 of 22), and quadriceps atrophy in 54.5% (12 of 22). Fourteen knees (63.6%) had Grade 2 plica based on thickness. Twelve knees demonstrated (54.5%) Grade 2 intermediary effusion. Plica was fenestrated in three patients (13.6%). All patients regained full range of motion. Lysholm knee scale scores were compared prior to and postsurgery (preoperative status, 65.22 ± 7.41 vs. postoperative status, 89.43 ± 8.72) which revealed a significant clinical improvement (P < 0.001). Average visual analog scale (VAS) scores (0 – no pain, 10 – excruciating pain) when compared demonstrated a mean improvement was 4 points; from 6 points before surgery and 2 points' postsurgery after a mean follow-up of 3 months. About 68% of patients after arthroscopic resection had an average VAS score of 0 point and were totally pain free. Conclusion: Noninvasive capability of MRI can be used as a screening method in the diagnosis of mediopatellar plica syndrome and should be included in the differential diagnosis of internal derangement of the knee.
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Effects of raw vegan diet on periodontal and dental parameters p. 357
Fazele Atarbashi-Moghadam, Soofieh Moallemi-Pour, Saede Atarbashi-Moghadam, Soran Sijanivandi, Alireza Akbarzadeh Baghban
DOI:10.4103/tcmj.tcmj_161_19  
Objectives: Macronutrients and micronutrients present in different types of diet could influence different aspects of both inflammatory and immune responses; thereby, diets could influence oral health and the periodontal condition. The raw vegan diet is a subset of vegetarianism in which only uncooked plant-derived foods are consumed. The present study's aim was to evaluate the effect of the raw vegan diet on periodontal and dental health parameters. Materials and Methods: A total of 118 participants (59 raw vegans and 59 controls) were interviewed about their level of education and oral health habits. Samples of unstimulated whole saliva were collected for pH analysis, and dental and periodontal parameters were examined. Then, statistical analysis was performed. Results: Raw vegans had better oral hygiene (P = 0.001). The decayed-missing-filling indices were relatively equal in both groups. The probing depth, bleeding on probing (BOP), and simplified oral hygiene index were significantly lower in raw vegans (P = 0.047, P = 0.017, and P = 0.001, respectively). Multiple regression analyses disclosed that probing depth and BOP were significantly related to debris index. Conclusion: Based on this study's results, it can be presumed that the better periodontal condition in raw vegans is a result of their better oral care and lifestyle.
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Assessment of common risk factors and validation of the Gail model for breast cancer: A hospital-based study from Western India p. 362
Naveen Kumar, Vinit Singh, Garima Mehta
DOI:10.4103/tcmj.tcmj_171_19  
Objective: Modified Gail Model is a noninvasive, easy to implement risk estimation tool for absolute breast cancer risk. It was developed with data collected from non African American females and further modified for African-American, the Hispanic, and Native American populations. The use of this model for population outside the US and European country is not yet validated. We evaluated the prevalent risk factors and the effectiveness of the Gail model for risk assessment in our local Indian population. Materials and Methods: A retrospective analysis of a prospectively maintained database was conducted on patients treated between 2008 and 2013. Six hundred and fifty patients were included in each group. Six questions were taken as per the breast cancer risk assessment tool calculator. A value of over 1.67% was taken as a high risk for breast cancer development. Results: The mean age of the participant was 50 ± 21.3 years in cases and 41 ± 16.4 years incontrols. Age and age at first childbirth >30 years were found to be significant and associated with increased risk of breast carcinoma, but the age at menarche, family history, previous breast biopsy, and atypical hyperplasia was no significant. The Gail model was assessed, and sensitivity was 10.30% and 96.30% specificity for our population. Positive and negative predictive values were 73.62% and 51.77%. Conclusion: Our study concluded that the Gail model is not an appropriate risk assessment tool for the population in its present form. For the future application of this model, we need to perform a bigger study with a higher sample size representing a maximum number of local variabilities in the Indian population.
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Significant association factors of bone mineral density in Taiwan adults p. 367
Tzyy-Ling Chuang, Mei-Hua Chuang, Chun-Hung Lin, Shih-Chin Chou, Yuh-Feng Wang
DOI:10.4103/tcmj.tcmj_113_19  
Objective: To examine the biofactors associated with bone mineral density (BMD) in southern Taiwanese adults. Materials and Methods: The medical records of 3242 adults who underwent health examinations between June 2014 and February 2018 at a regional hospital in southern Taiwan were reviewed. The data collected included health history, anthropomorphic characteristics, clinical laboratory results, biochemical parameters, and BMD. The data were used to identify the biofactors associated with BMD/T-scores at the lumbar spine and femoral neck by multivariate linear regression analysis with the stepwise method. Results: The mean age of the patients was 58.1 years, and 71.4% were male. Factors positively correlated with BMD and the T-score included body mass index (BMI), male gender, calcium, and creatinine. Age, alkaline phosphatase (ALP), triiodothyronine, serum thyroxine, low-density lipoprotein cholesterol, and a history of hyperlipidemia were negatively correlated with BMD and the T-score. Conclusion: The associated biofactors reported here were similar to and had similar relationships as the biofactors identified in previous literature reports. Not all of the sites examined for BMD were influenced by the same association factors, except for BMI, male gender, age, and ALP, implying that the bone remodeling processes that shape BMD involve a complex regulatory network and demonstrating that our extracted factors are the most useful for clinical practice.
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Effectiveness of the doula program in Northern Taiwan p. 373
Chia-Chi Chen, Jia-Fu Lee
DOI:10.4103/tcmj.tcmj_127_19  
Objective: The cesarean section rate in Taiwan is 32%–34%, exceeding the rate that the World Health Organization considers reasonable. A doula is a trained woman who provides physical, emotional, and informational support to pregnant women before, during, and after delivery. This study investigated the effectiveness of a new doula program in Northern Taiwan. Materials and Methods: A quasi-experimental research design was employed. Two hundred and twenty women, divided into an experimental group with doula services and a no-doula control group receiving routine hospital care, participated in the present study. Participants' basic information was collected; the study tools were the State-Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale, labor pain visual analog scale, a labor timetable, and Mother's Level of Childbirth Satisfaction Rating Scale, which were distributed to participants during the postpartum hospitalization period. Results: The highest level of satisfaction was with the spouse in the control group and the doula in the experimental group. The results indicated that the childbirth process involved considerable anxiety in both groups. After delivery, the doula group exhibited a greater reduction in anxiety than the control group, but the reduction was not significant; however, a statistically significant difference was identified in the cesarean section (C/S) rate (13.0% vs. 43.2%) and normal spontaneous delivery (NSD) rate (87.0% vs. 56.8%) between the doula and control groups after controlling for the factor of primara. Conclusion: Providing continuous doula program to pregnant women requiring labor support may reduce the C/S rate and increase the NSD rate. The regression model showed that the factors including high prenatal anxiety, total time needed for doula accompaniment, and epidural and analgesics use were associated with labor women receiving C/S. The factors of continuous doula support and oxytocin use were associated with receiving NSD.
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Retrospective analyzing the effects of nerve block on postoperative pain management after total knee arthroplasty p. 380
Yu-Ning Huang, Jen-Hung Wang, Po-Kai Wang
DOI:10.4103/tcmj.tcmj_199_19  
Objective: Total knee arthroplasty (TKA) is usually associated with moderate-to-severe postoperative pain. Our study investigated the possible benefits of the use of nerve blocks (NBs), including pain score reduction, the rescuing dosage of morphine, the timing of ambulation, and the length of stay (LOS) in the hospital. Materials and Methods: We included patients who underwent unilateral primary TKA due to primary knee osteoarthritis under general anesthesia with laryngeal mask airway. The control group only received oral pain medication with rescuing morphine injections, whereas the NB group received oral pain medication with an NB and rescuing morphine injections. We collected data on the patients' basic characteristics, postoperative visual analog scale (VAS), the dosage of rescuing morphine over 3 days, time to ambulation, and LOS in the hospital. Results: The NB group received significantly fewer morphine dose compared with the control group during postoperative days 1 to 3. There were no statistically significant differences between the NB and control groups on days 1 and 2 in the VAS score, and the VAS score was significantly lower in the NB group on postoperative day 3. The NB group had a significantly shorter time to ambulation compared with the control group. LOS did not differ significantly between the NB and control groups. Conclusion: Patients, who underwent TKA under general anesthesia with laryngeal mask airway (LMAGA) receiving NB for postoperative pain, needed less dosage of morphine and had the trend of having lower VAS. There was no association with LOS between two groups, but time to ambulation might be decreased with NB group. Some limitations might need to be further investigated in future study, such as NB regimens, knee function after TKA, muscle power, information after discharge, and NB-related complications.
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Prognostic value of peak lactate during cardiopulmonary bypass in adult cardiac surgeries: A retrospective cohort study p. 386
Hsiao-Hui Yang, Jui-Chih Chang, Jin-You Jhana, Yi-Tso Cheng, Yen-Ta Huang, Bee-Song Chang, Shen-Feng Chao
DOI:10.4103/tcmj.tcmj_215_19  
Objective: Tissue hypoperfusion during cardiopulmonary bypass (CPB) affects cardiac surgical outcomes. Lactate, an end product of anaerobic glycolysis from oxygen deficit, is a marker of tissue hypoxia. In this study, we aimed to identify the prognostic value of blood lactate level during CPB in predicting outcomes in adults undergoing cardiac surgeries. Materials and Methods: We retrospectively reviewed the medical records of patients who underwent cardiac surgeries with CPB from January 2015 to December 2015. Data about the characteristics of patients, preoperative status, type of surgery, and intraoperative lactate levels were collected. The outcomes were in-hospital mortality and complications. The receiver operating characteristics (ROC) curves were used to assess the ability of peak lactate level during CPB in predicting in-hospital mortality. Results: A total of 97 patients, including 61 who underwent emergent or urgent surgery, were enrolled. The types of surgery included coronary artery bypass grafting (CABG, n = 52), valve surgery (n = 27), combined surgery (CABG and valve surgery, n = 4), great vessel surgery (including aortic dissection, n = 9), and others (n = 5). The median CPB time was 139 min (interquartile range = 120–175). The median initial lactate and peak lactate levels during CPB were 0.9 and 4.2 mmol/L, respectively. In-hospital mortality was 14.4%, which was significantly associated with age and peak lactate level in the multivariate logistic regression model. When the peak lactate level during CPB reached 7.25 mmol/L, in-hospital mortality could be predicted with an area under the ROC curve of 0.75 (95% confidence interval: 0.59–0.90; P = 0.003), with a sensitivity of 57% and specificity of 93%.Conclusion: Hyperlactatemia during CPB was associated with increased in-hospital mortality. Thus, early detection of such conditions and aggressive postoperative care are important.
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ORIGINAL ARTICLE - MEDICAL EDUCATION Top

A qualitative study on negative attitude toward electrocardiogram learning among undergraduate medical students Highly accessed article p. 392
May Honey Ohn, Urban D Souza, Khin Maung Ohn
DOI:10.4103/tcmj.tcmj_91_19  
Objective: Negative affect state toward learning has a substantial impact on the learning process, academic performance, and practice of a particular subject, but such attitude toward electrocardiogram (ECG) learning has still received relatively little attention in medical education research. In spite of the significant emphasis in investigating ECG teaching method, the educators would not be able to address ECG incompetency without understanding the negative perception and attitude toward ECG learning. The purpose of this study was to assess the undergraduate students' difficulties in ECG learning and hence help educators design appropriate ECG learning curriculum to instill competent skill in ECG interpretation based on this outcome. Materials and Methods: A total of 324 undergraduate preclinical (year 2) and clinical (year 3–5) medical students participated in this study. The research design used thematic analysis of an open-ended questionnaire to analyze the qualitative data. Results: The thematic analysis detected five major emergent themes: lack of remembering (18.2%), lack of understanding (28.4%), difficulty in applying (3.6%), difficulty in analysis (15.1%), and difficulty in interpretation (17.8%), of which addressing these challenges could be taken as a foundation step upon which medical educators put an emphasis on in order to improve ECG teaching and learning. Conclusion: Negative attitude toward ECG learning poses a serious threat to acquire competency in ECG interpretation skill. The concept of student's memorizing ECG is not a correct approach; instead, understanding the concept and vector analysis is an elementary key for mastering ECG interpretation skill. The finding of this study sheds light into a better understanding of medical students' deficient points of ECG learning in parallel with taxonomy of cognitive domain and enables the medical teachers to come up with effective and innovative strategies for innovative ECG learning in an undergraduate medical curriculum.
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CASE REPORTS Top

Pelvic myoma arising from vaginal cuff after hysterectomy: A case report and literature review p. 398
Yi-Jen Ho, Pei-Chen Li, Chiu-Hsuan Cheng, Dah-Ching Ding
DOI:10.4103/tcmj.tcmj_169_19  
Leiomyomas are the most common benign gynecologic tumors and the most common surgical indication for hysterectomy or myomectomy. Recurrent pelvic leiomyomas or vaginal leiomyomas are rare. We report the case of a 60-year-old woman with a history of a cesarean total hysterectomy 25 years before presenting to us, who developed a pelvic leiomyoma arising from the vaginal cuff. The patient underwent single-port laparoscopic tumor excision and recovered uneventfully.
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Hyperviscosity retinopathy as the initial presentation of aggressive multiple myeloma p. 401
Hua-Hsuan Kuo, Elizabeth P Shen
DOI:10.4103/tcmj.tcmj_214_19  
Multiple myeloma (MM) is a hematologic malignancy resulting from the uncontrolled proliferation of neoplastic plasma cells and the excessive production of monoclonal immunoglobulins, both of which may lead to hyperviscosity retinopathy. Here, we present a 56-year-old male who had progressive painless loss of vision for 1 month. Ophthalmic examination revealed hyperviscosity retinopathy with bilateral central retinal vein occlusion-like appearance. Hematologic assessment revealed immunoglobulin A MM. Although the patient was treated with chemotherapy and autologous stem cell transplantation soon after referral, he did not survive due to the aggressive course of the disease. We highlight the importance of the ophthalmic presentation of MM. Early recognition and referral to an oncologist can lead to timely diagnosis and appropriate management.
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IMAGES IN CLINICAL MEDICINE Top

Xp11 translocation renal cell carcinoma with vertebral metastasis presenting with low back pain and sciatica p. 404
Yen-Chang Chen, Yung-Hsiang Hsu, Cheng-Ling Lee, Pau-Yuan Chang
DOI:10.4103/tcmj.tcmj_70_20  
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CONTENTS INDEX Top

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AUTHOR INDEX Top

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