Τετάρτη 2 Ιανουαρίου 2019

Urology



A novel intraoperative physician-assigned grading score to predict postoperative return of potency at 1 year after robotic-assisted laparoscopic prostatectomy Highly accessed articlep. 61
Rajesh R Bajpai, Shirin Razdan, Marcos A Sanchez, Sanjay Razdan
DOI:10.4103/iju.IJU_158_18  
Introduction: We examined a novel method of grading nerve sparing in robotic-assisted laparoscopic radical prostatectomy to better predict the potency outcomes of patients at 1-year after surgery. This grading (scale) was based on the surgeon's criteria of intraoperative findings during completion of nerve sparing. This grading was then analyzed statistically to validate its association with potency outcomes. Methods: We devised a study module based on measurable visual cues intraoperatively where the surgeon risk stratified the surgery into four grades depending on the completeness of nerve sparing, keeping in mind the known parameters influencing potency outcomes. A novel grading scale was then proposed and used in this study for the same. We prospectively collected data and retrospectively analyzed 425 patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) at a high-volume center by a single surgeon. Results: At 1 year of follow-up, it was found that age, laterality of nerve preservation, weight of prostate, and the surgeon-assigned grading were all statistically significant independent predictors of return of potency in terms of satisfactory penetrative intercourse >50% of times and Sexual Health Inventory for Men ≥17. However, prostate-specific antigen was found not to be a predictor of the same. Conclusions: Intraoperative physician-assigned grading was found to be the single most significant predictor of the return of potency at 1-year post-RALP.
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Renal transplantation into optimized abnormal lower urinary tract – Impact on graft outcomes, patient survival, and complicationsp. 67
Selvin Theodore Jayanth, Anuj Deep Dangi, Rajiv Paul Mukha, Santosh Kumar, Santosh Varughese, Vinoi G David, Anna Valson, J Chandrasingh, Antony Devasia, Nitin Kekre
DOI:10.4103/iju.IJU_203_18  
Introduction: Literature regarding the outcomes of renal transplant in patients with abnormal lower urinary tracts (LUTs) is conflicting. The study aimed to determine the graft outcomes and complications of renal transplantation in an optimized abnormal LUT as compared to those with a normal LUT. Materials and Methods: In this single-center retrospective-matched cohort study, we identified 31 patients with an optimized abnormal LUT in our transplant database between 2006 and 2016 (Group A) and selected an equal number of matched controls (Group B). The primary outcome was graft survival, and secondary outcomes were overall survival and complications.Results: The median age was 24 years (range: 12–45), and the median duration of follow-up was 36 months in both groups. On Kaplan–Meier analysis, the estimated mean graft survival was 106 months (confidence interval [CI]: 91-120) in Group A versus 128 months (CI:117-139) in Group B (P = 0.47, log-rank analysis). On subgroup analysis of Group A, augmented bladders had the poorest mean survival (81 months, CI: 56–106), P = 0.09). The mean estimated patient survival was comparable between Group A and B (109 months, CI: 96–122 versus 139 months, CI: 134–144), P = 0.13). Infective complications (27 episodes vs. 1) and re-admissions (77 vs. 30) were significantly higher in Group A (P = 0.04 and P < 0.01). Clean intermittent catheterization was a risk factor for infections (63% vs. 37%, P = 0.033, odds ratio: 5). Conclusions: The graft and overall survival was comparable at 3 years in both groups. Infective complications were higher in Group A.
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CASE REPORTSTop

Carbon dioxide insufflation to control intractable bleeding during transurethral resection of bladder tumorp. 73
Minoru Kobayashi, Takao Kamai
DOI:10.4103/iju.IJU_263_18  
We describe a method to manage severe bleeding during transurethral resection (TUR) of a giant bladder tumor, in which vision was impaired by the bleeding. The use of carbon dioxide gas as an alternative to irrigation fluid for bladder inflation provided a better view to safely control the intractable bleeding.
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Urethral metastasis with neuroendocrine differentiation in a patient with prostate cancer treated with hormone deprivationp. 75
Karamveer Sabharwal, Anant Kumar, Andleeb Abrari
DOI:10.4103/iju.IJU_175_18  
Adenocarcinoma prostate treated with hormone deprivation may evolve into a neuroendocrine differentiated tumor. Usually visceral metastasis are seen in neuroendocrine tumors. We present a case of neuroendocrine differentiated urethral metastasis from a hormone deprived prostate cancer.
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Symmetrical peripheral gangrene of all four limbs: An unusual complication of ureteroscopyp. 78
Pankaj N Maheshwari, Nick Okwi, Anant P Pore
DOI:10.4103/iju.IJU_33_18  
Ureteroscopy (URS) is a commonly performed and a safe urological intervention. However, potentially serious infective complications are possible after URS. A young nondiabetic woman developed severe Gram-negative septicemia after ureteroscopy for a lower ureteric calculus. The sepsis progressed to symmetrical peripheral gangrene of all the four limbs. She required left below-elbow amputation, right below-knee amputation, and loss of all toes and digits of the other two limbs.
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UROLOGICAL IMAGESTop

Prominent swelling on erection: Perineal angiomyxoma as a rare entityp. 81
Shantanu Tyagi, Ravimohan Suryanarayan Mavuduru, Girdhar S Bora, Sudheer Kumar Devana, Aditya Prakash Sharma
DOI:10.4103/iju.IJU_221_18  
Perineal angiomyxoma is a rare entity, more commonly seen in females. We report a case of a 44 year old male who presented with a perineal swelling which became prominent with penile erections. Magnetic Resonance Imaging (MRI) revealed a T1 hypointense and T2 hyperintense midline lesion (4.6 × 2.5 × 5 cm) in relation to corpus spongiosum, with ill defined fat planes with the bulbospongiosus muscle and progressive enhancement on dynamic contrast sequence. A differential diagnosis of soft tissue sarcoma or hemangioma was made and the mass was completely excised via a midline perineal incision. The histopathology revealed features consistent with angiomyxoma.
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VIDEOTop

Casale's tube with VQZ stoma: An alternative to "double Monti"p. 83
Nikhil Khattar, Anurag Singla, Rajeev Sood, Arif Akhtar, Dushiant Sharma
DOI:10.4103/iju.IJU_194_18  
In situations requiring an ileal segment for performing a Mitrofanoff cathetrisable urinary diversion, occasionally a "Double Monti" is needed to achieve a length for the cathetrisable channel to conveniently reach the abdomen of an adult. Casale's tube is an alternative where it can provide a jointless tube with adequate length. The video demonstrates the procedure in an adult with a neurogenic acontractile bladder who had developed a panurethral stricture because of years of self catheterization. "VQZ" technique of stoma formation is helpful in prevention of stenosis.
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UROSCANTop

Olaparib: Transcending mutational barriersp. 85
Abhishek Chandna
DOI:10.4103/iju.IJU_292_18  
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Biochemical recurrence after radical prostatectomy: Current status of its use as a treatment endpoint and early management strategies
Barrett Z McCormick, Ali M Mahmoud, Stephen B Williams, John W Davis

Indian Journal of Urology 2019 35(1):6-17

Prostate cancer is one of the most common urological malignancies managed by a practicing urologist. Treatment strategies are varied, but radical prostatectomy (RP) remains a viable and commonly used option for many patients. A continuing challenge in the management is how to approach a patient who has biochemical recurrence (BCR) after RP. There are no consensus guidelines on the appropriate strategy, and the current recommendations, although useful, are at times confusing. The natural history of BCR is heterogeneous. Published studies aid in the clinician&#39;s ability to predict patients most likely to recur; however, this remains inexact. In addition, recent changes in the recommendations for disease screening, as well as technological advances, have added to the already challenging task of the clinician. The objective of this review is to provide an up-to-date summary of the definitions, diagnosis, and management strategies of BCR after RP. This narrative review was conducted by searching Medline for all relevant articles in English with the key terms of biochemical recurrence, prostate cancer, management, and other relevant terms. Information was compiled and reviewed for relevance to the article. Consideration was given to all articles with sufficient evidence including systematic review, retrospective studies, and clinical trials.


Female underactive bladder – Current status and management
Tammer Yamany, Marlie Elia, Jason Jihoon Lee, Ajay K Singla

Indian Journal of Urology 2019 35(1):18-24

Underactive bladder (UAB) is defined by the International Continence Society as a symptom complex characterized by a slow urinary stream, hesitancy, and straining to void, with or without a feeling of incomplete bladder emptying sometimes with storage symptoms. Until recently, the topic has received little attention in the literature probably due to a lack of consistent definitions and diagnostic criteria. We performed a literature review to identify articles related to the diagnosis and management of UAB, specifically in female patients. UAB is a common clinical entity, occurring in up to 45&#37; of females depending on definitions used. Prevalence increases significantly in elderly women and women who live in long-term care facilities. The exact etiology and pathophysiology for developing UAB is unknown, though it is likely a multifactorial process with contributory neurogenic, cardiovascular, and idiopathic causes. There are currently no validated questionnaires for diagnosing or monitoring treatment for patients with UAB. Management options for females with UAB remain limited, with clean intermittent catheterization, the most commonly used. No pharmacotherapies have consistently been proven to be beneficial. Neuromodulation has had the most promising results in terms of symptom improvement, with newer technologies such as stem-cell therapy and gene therapy requiring more evidence before widespread use. Although UAB has received increased recognition and has been a focus of research in recent years, there remains a lack of diagnostic and therapeutic tools. Future research goals should include the development of targeted therapeutic interventions based on pathophysiologic mechanisms and validated diagnostic questionnaires.


Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study
Smita Pattanaik, Harbhupinder Singh Sandhu, Ravimohan Suryanarayan Mavuduru, Shrawan Kumar Singh, Arup Kumar Mandal

Indian Journal of Urology 2019 35(1):25-33

Introduction: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. Methods: Men &#8805;45 years of age, with an International Prostate Symptom Score (IPSS) &#8805;8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. Results: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P &#60; 0.05) as compared to the baseline. However, there were no significant differences between the two drugs with respect to extent of observed effect and which drug was prescribed 1st in the sequence respectively (P &#62; 0.05). Significant period effect was observed (P &#60; 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. Conclusion: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa.


Changes in blood pressure, blood sugar, and quality of life in patients undergoing pheochromocytoma surgery: A prospective cohort study
Pradeep Prakash, Rashmi Ramachandran, Nikhil Tandon, Rajeev Kumar

Indian Journal of Urology 2019 35(1):34-40

Introduction: Pheochromocytoma surgery is associated with significant hemodynamic and metabolic changes that require post-operative monitoring. We prospectively evaluated the trends of blood pressure, blood sugar, body mass index (BMI), and quality of life (QoL) changes in a cohort of patients undergoing pheochromocytoma surgery to determine the minimum duration of monitoring and assess factors that could predict these changes. Materials and Methods: Consecutive patients undergoing surgery for pheochromocytoma over a 20-month period were included in this ethics review board-approved, prospective cohort study. Blood pressure and sugar levels were serially monitored using a fixed protocol in the perioperative period and subsequently at 3 months after surgery. BMI and QoL (using World Health Organization Quality of Life [WHOQOL-BREF] questionnaire) were recorded at baseline and 3 months. Changes were compared and assessed for the predictive factors. Results: Twenty-six patients undergoing 31 procedures were included in the study of whom 8 (30&#37;) developed hypotension and 4 (15&#37;) developed hypoglycemia after surgery. All hypotension episodes occurred within 6 hours of surgery. However, while 3 of the 4 patients who developed hypoglycemia manifest in the first 4 h after surgery, one occurred after 12 h. Occurrence of hypotension correlated with preoperative 24-h urinary vanillylmandelic acid (VMA) levels (P &#61; 0.02) and the total daily dose of prazosin (P &#61; 0.04). Out of 21 hypertensive patients, 7 (33&#37;) had persistent hypertension (HTN) at 3 months and this was associated with age (P &#61; 0.04) and diabetes mellitus (DM) at presentation (P &#61; 0.04). Among six diabetic patients, 1 (16&#37;) had persistent DM. There was significant increase in the BMI (P &#60; 0.0001) and in WHOQOL-BREF scores postoperatively. Conclusions: Hypotension occurs in 30&#37; patients and hypoglycemia in 15&#37; after pheochromocytoma surgery. Hypotension occurs immediately but hypoglycemia may manifest upto 12h after surgery. Older, diabetic patients are more likely to have persistent HTN. Surgery results in increase in BMI and improvement in QoL.


Urethral stricture after bipolar transurethral resection of prostate – truth vs hype: A randomized controlled trial
Bharath N Kumar, Anand Srivastava, Tapan Sinha

Indian Journal of Urology 2019 35(1):41-47

Introduction: Bipolar transurethral resection of prostate (B-TURP) was introduced as an alternative procedure to minimize the surgical complications of monopolar TURP (M-TURP). However, there are concerns about increased incidence of stricture urethra (SU) post B-TURP. This study was designed to analyze the incidence of SU among patients undergoing M-TURP versus B-TURP. Materials and Methods: This is a randomized controlled, single-blinded study; randomization was performed using a stratified permuted randomization algorithm (1:1 ratio) and only the patients were blinded. Both M-TURP and B-TURP were performed with a 26 Fr resectoscope; the electrosurgical generators were Karl Storz Autocon II 400 and Olympus UES-40 SurgMaster (TUR in saline [TURIS] method), respectively. Follow-up visits were scheduled at 3, 6, and 12 months post surgery and patients with lower urinary tract symptoms and a maximum urinary flow rate of &#60;10 ml/sec on uroflowmetry underwent retrograde urethrography to assess for development of SU. Results: Forty patients were randomised to each arm. None developed SU in the monopolar group, whereas there were three cases in the bipolar group (P &#61; 0.2). Among these three patients, two belonged to the failed medical management subgroup and one to the refractory urinary retention subgroup (P &#61; 1.0). Conclusion: The incidence of SU following B-TURP using the TURIS system was comparable to the conventional M-TURP. Moreover, the incidence of SU was same for both the techniques when sub-grouped according to the indication for surgery that is failed medical management versus refractory urinary retention.


Comparison of antegrade percutaneous versus retrograde ureteroscopic lithotripsy for upper ureteric calculus for stone clearance, morbidity, and complications
Amilal Bhat, Vikash Singh, Mahakshit Bhat, Nikhil Khandelwal, Akshita Bhat

Indian Journal of Urology 2019 35(1):48-53

Introduction: The optimal management of upper ureteric calculus remains controversial. We compare the outcomes of antegrade percutaneous ureterolithotripsy (APCUL) with retrograde ureteroscopic lithotripsy (URSL) for upper ureteric calculus with respect to stone clearance, morbidity, and complication rates. Materials and Methods: This prospective study was carried out from December 2014 to June 2016. A total of 117 patients with upper ureteric calculus sized (10&#8211;20) mm who underwent APCUL or URSL were included in the study. Results: APCUL and URSL were performed in 64 and 53 patients, respectively. The mean age and stone size were comparable between the two groups. The stone clearance rate at 1-month follow-up was 93.75&#37; in the antegrade group and 81.13&#37; in the retrograde group (P &#61; 0.036). Mean anaesthesia time was significantly longer for the APCUL group while the actual mean operative time was significantly longer for the URSL group (P &#60; 0.001). The overall complication rate was higher in antegrade group (P &#61; 0.804), whereas most of the major complications (Clavien Grade III or more) occurred only in the URSL group (P &#61; 0.007). Blood transfusion was required only in the APCUL group (7.8&#37; versus 0&#37;; P &#61; 0.50). In the URSL group, stone retropulsion occurred in four patients, of which three subsequently required shock wave lithotripsy and one required percutaneous nephrolithotomy in a second sitting. Conclusion: APCUL has better stone-free rates as compared to URSL for an upper ureteric calculus of size 10&#8211;20 mm. Although the postoperative minor complications are higher in the antegrade group, severe complications occurred only in the retrograde group. Hence, antegrade approach can be considered as the preferred option to achieve better stone clearance in a single sitting with acceptable morbidity and complication rates.


Are we ready for urological subspecialty-based practice in India? The resident's perspective
Ashwin Sunil Tamhankar, Ravindra Sabnis, Gagan Gautam

Indian Journal of Urology 2019 35(1):54-60

Introduction: In the current era, every broad specialty has diversified into many subspecialties including urology, which is one of the most dynamic fields. The concept of early sub-specialization relies on excelling in a niche area of interest. While this concept is appealing to the most, no formal evaluation of our residency programs has ever been conducted with regard to their adequacy in terms of equipping residents to make informed sub-specialization choices. We performed a survey amongst urological residents, in an attempt to gather information on some unanswered questions related to our residency training programs and the concept of sub-specialization. Methods: Using the Delphi principles, we conducted a survey consisting of 46 questions, amongst the Indian Urological residents (n &#61; 85), to assess the overall exposure to various subspecialties during their residency program, and the inclination of residents towards them. Results: Residents get a fair exposure to endourology, uro-oncology, female urology and reconstructive urology during their residency. However, the same did not hold true for pediatric urology, andrology and laparoscopic/robotic surgery. 90&#37; of the residents expressed an inclination towards academic practice, while 76.5&#37; were interested in sub-specialization. 60&#37; of the residents felt that they had obtained adequate exposure during residency to make a decision in this regard. Less than 20&#37; were inclined towards female urology, andrology or pediatric urology as a career option. Conclusion: There is a growing interest and inclination amongst Indian Urological residents to attain expertise in sub-specialised fields. However, our current residency programs need consolidated efforts to ensure an adequate exposure to all the aspects of Urology, especially in the subspecialties of pediatric urology, andrology and minimally invasive urology. Training should be optimized to a level, which enables the residents to take a well informed decision regarding their choice of subspecialised career path.

Septic cavernous sinus thrombosis as a complication of sphenoid sinusitis.Isolated sphenoid sinusitis is a rare disorder and may present with severe complications due to its proximity to the orbital and intracranial areas. We report a 13-year-old boy hospitalized for septic shock with fever of unknown origin. Facial palsy was later noted. Brain magnetic resonance imaging showed a sphenoid mass and right cavernous sinus and internal jugular vein thrombosis. Biopsy revealed chronic rhinosinusitis. Complete recovery followed by an incision/drainage procedure and antibiotic treatment. Acute sphenoid sinusitis should be included in the differential diagnosis of septic manifestations mimicking central nervous system infection or cranial nerve palsy.

Introduction Top


Acute paranasal sinusitis is a common disorder in the pediatric population, and orbital complications, mostly resulting from ethmoid sinusitis, account for 80% of cases[1]. Intracranial complications such as meningitis and cavernous sinus thrombosis accounted for only 13% of cases and were mainly secondary to frontal sinusitis and rarely induced by sphenoiditis[1]. We herein report a 13-year-old boy who presented with fever of unknown origin, septic shock accompanied by right neck pain, and facial palsy due to sphenoiditis-induced right cavernous sinus and internal jugular vein thrombosis. Complete recovery followed by an incision/drainage procedure and antibiotic treatment. Acute sphenoiditis should be included in the differential diagnosis of septic manifestations mimicking central nerve system (CNS) infection or cranial nerve palsy.


  Case Report Top


A 13-year-old boy with a pertinent medical history of only allergic rhinitis was hospitalized for septic shock with fever of unknown origin. He had gone diving 10 days prior to admission (PTA). Six-day PTA, he had a fever (38°C) followed by headache, nausea, and vomiting but no diarrhea. Pertinent serologic examination at another hospital revealed white blood cells (WBCs) 10,170/μL, segments 92.6%, and C-reactive protein (CRP) 28.67 mg/dL. The chest radiograph and urinalysis showed no abnormalities. The family refused a lumbar puncture. Intravenous (IV) penicillin was given and the fever gradually subsided. Four-day PTA, right neck pain occurred without a history of trauma or any particular findings in the aforementioned area. One-day PTA, the fever rose to 39°C; right neck pain progressed and he became drowsy. Upon admission, his body temperature was 36.9°C, pulse rate 96/min, respiratory rate 18/min, and blood pressure 70/30 mmHg. Physical examination showed no abnormalities except tenderness on the right side of the neck level II of the submandibular angle without nuchal rigidity, cervical lymphadenopathy, wound, or skin discoloration. Dopamine was given for his shock status on admission. Laboratory data were WBC – 7510/μL, bands – 49%, segments – 32%; platelets – 13,000/μL; CRP – 31.21 mg/dL; slightly elevated fibrinogen/D-dimer; and a normal prothrombin time/activated partial thromboplastin time (PT/aPTT). Fiberscopic examination revealed no evidence of deep neck infection. Under suspicion of atypical infection, IV penicillin and levofloxacin were started and his clinical condition improved. Dopamine was discontinued on the 2nd hospital day (HD), and his fever subsided on the 5th HD. However, right neck pain persisted accompanied by right peripheral facial palsy and ptosis but no visual impairment. Tests for serum Lyme antibody IgG and IgM were normal. Brain magnetic resonance imaging (MRI) on the 6th HD showed a right sphenoid sinus mucocele with a right cavernous sinus and internal jugular vein thrombosis [Figure 1]. Endoscopic incision/drainage was performed. Pathology revealed chronic sphenoiditis. Blood cultures grew Peptostreptococcus; anaerobic pus cultures grew Prevotella loescheii, both sensitive to penicillin. Pus acid-fast stain and tuberculosis cultures were negative. After completing a 4-week course of penicillin and ceftriaxone (levofloxacin was shifted to ceftriaxone due to elevating liver enzymes), he was discharged with full recovery of cranial nerve palsy and no neck pain.
Figure 1: Axial slice on a T1-weighted image after gadolinium–diethylenetriaminepentacetate administration focusing on the cavernous sinus (a), jugular fossa (b), and coronal section of the jugular vein level (c). There is nonenhancement in the right cavernous and sigmoid venous sinus, contiguous with the jugular vein, compatible with sphenoiditis-resultant right cavernous sinus thrombosis and deep venous thrombosis of the right cerebrum and neck. T2-weighted image axial section at the mid sphenoid level (d). There is mucus in the right sphenoid sinus (white arrow), right mastoiditis, and a bright signal in the right sigmoid sinus and jugular fossa indicating nonflow void in the venous sinus and jugular vein

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  Discussion Top


A thromboembolic event is rare in the pediatric population. Central venous catheter-related thrombosis is the most common etiology of pediatric venous thrombosis followed by infection, inflammation, hypercoagulability, malignancy, and dehydration[2]. Our patient had no medical history of any inflammatory disease or thromboembolic events. Likewise, he had no central venous catheter insertion during hospitalization. Clinical and laboratory data showed no evidence of malignancy or dehydration. There was no thrombocytosis and PT/aPTT levels were normal, which were not consistent with hypercoagulation syndrome. His urinalysis was normal, excluding hypercoagulable state-induced thromboembolic complications of nephrotic syndrome. Thus, infection (sphenoiditis)-related right cavernous sinus and internal jugular vein thrombosis were most likely in our case.

The sphenoid sinus has been referred as the "neglected sinus" and is absent until the age of 1 year. It becomes visible through imaging and is clinically relevant between the ages of 5 and 15[3]. The low incidence of isolated sphenoiditis compared with infection in other paranasal sinuses may be due to fewer drainage problems secondary to few mucous secreting cells along the pseudostratified ciliated epithelium lining of the sphenoid sinus[4]. Thus, isolated sphenoid sinusitis (ISS) is uncommon, affecting only 1–2.7% of patients with paranasal sinusitis[5].

The diagnosis of ISS is usually missed or delayed until neurological symptoms become apparent [6],[7]. In acute cases, 86% of patients have headaches, followed by nasal (35%) and ocular (30%) symptoms[8]Staphylococcus aureus is responsible for 24% of acute sphenoiditis, followed by Streptococcal species. Anaerobes (Peptostreptococcus, PrevotellaFusobacterium, and Porphyromonas species), Gram-negative bacilli (Klebsiella pneumoniaeEscherichia coli, and Pseudomonas aurigunosa)[3], and fungal pathogens (Aspergillus xavus and Aspergillus fumigatus) are mostly encountered in chronic sphenoiditis[9]. Diving/swimming is associated with acute severe sphenoid sinusitis, whereas allergic rhinitis is related to acute nonsevere forms[3]. Our patient had allergic rhinitis. This may have caused sinusitis leading to sphenoid mucocele formation. Minor trauma and forceful entry of water into the nose during diving may aggravate the progression of sphenoiditis, causing intracranial complications from right cavernous sinus and internal jugular vein thrombosis.

There are many recent reports of ISS presenting with headache and ipsilateral oculomotor nerve or abducens nerve palsy [6],[7]. Because indistinct nasal symptoms are often encountered, ISS is difficult to diagnose in the acute stage, so a high index of suspicion is necessary for early and accurate diagnosis. Neurological symptoms including headache which does not respond to symptomatic treatment or septic manifestations mimicking CNS infections, tumors, or vascular diseases require further evaluation to exclude sphenoiditis. Another important disease in the differential diagnosis of child cranial nerve VII palsy is Lyme disease, and bilateral facial nerve palsy is virtually pathognomonic of this disease. However, the serum Lyme antibody test in our patient was negative. High-resolution computed tomography or MRI is the diagnostic study of choice for ISS[10]. Antibiotics for uncomplicated cases include the amoxicillin-clavulanate, cephalosporins, or fluoroquinolons, and treatment is given for about 4 weeks. Immediate surgical drainage is indicated for symptoms occurring >24 h or the presence of neurological/ocular complications, with transnasal endoscopic sphenoidotomy currently used most frequently[3].

In conclusion, acute sphenoiditis should be included in the differential diagnosis of headache not responding to symptomatic treatments or for septic signs and symptoms mimicking CNS infections or cranial nerve palsy.

Declaration of patient consent

The authors certify that the patient and his parents have obtained an appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient and his parents understand that his name and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.  

http://www.tcmjmed.com/article.asp?issn=1016-3190;year=2019;volume=31;issue=1;spage=63;epage=65;aulast=Chen

Tzu Chi Medical Journal

Female genital mutilation; culture, religion, and medicalization, where do we direct our searchlights for it eradication: Nigeria as a case study
Olalekan Olugbenga Awolola, NA Ilupeju

Tzu Chi Medical Journal 2019 31(1):1-4

Female genital mutilation (FGM) is a form of violence against the girls and the women and also an infringement into the rights of the women in the society. It is practiced mostly in Africa, but migration has revolutionized its spread to almost all parts of the world. The government and the constituted authorities, our traditional rulers, the legislative, the judiciary, and the law enforcement agents have the machineries to stop this inhuman behavior, but they lack the will and the necessary information about the incidence and consequences of FGM. The review involved Internet and literature search mostly those written on the African continent and some that were specific to Nigeria from 1999 to 2018. This article reviewed the spread, the obstetrics and the gynecological complications, the roles of the traditional circumcisers, and the negative and the positive roles of the caregivers, especially its medicalization in the abandonment of FGM in Nigeria. The article also looked critically at the best ways to achieve zero tolerance to FGM. To achieve the targeted zero tolerance to FGM, the identified factors have to be tackled holistically. 


The roles of anti-citrullinated protein antibodies in the immunopathogenesis of rheumatoid arthritis
Hui-Chun Yu, Ming-Chi Lu

Tzu Chi Medical Journal 2019 31(1):5-10

Rheumatoid arthritis (RA) is a common systemic autoimmune disease. Its major manifestation is persistent joint inflammation, which can lead to bone destruction and severe disability. The immunopathogenesis of RA is very complex, involving both innate and adaptive immune systems. Recently, the discovery of anti-citrullinated protein antibodies (ACPAs) has revolutionized the diagnosis and our understanding of the immunopathogenesis of RA. The presence of ACPAs is also closely linked to the disease activity of RA. Therefore, it is reasonable to believe that ACPAs and protein citrullination are key issues for the development of RA. We have summarized the recent study results in this review. The first theory concerning the pathogenesis of RA proposed that ACPAs link the well-known genetic and environmental risk factors for developing RA. However, due to the close association between joint inflammation and ACPAs, a more direct role of ACPAs in the immunopathogenesis of RA is anticipated. Within the past 10 years, many studies, including some of our own, have shown that ACPAs can promote an inflammatory response through complement activation, formation of neutrophil extracellular traps, and direct binding to key players, including monocytes, osteoclasts, and osteoblasts, in the mediation of bone destruction in the joints of RA patients. We also present some new perspectives and issues that need to be further investigated. 


Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig model
Kun-Chi Wu, Yu-Hsun Chang, Hwan-Wun Liu, Dah-Ching Ding

Tzu Chi Medical Journal 2019 31(1):11-19

Objectives: Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. Materials and Methods: The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC&#8211;HA coculture. Two healthy female minipigs weighing 30&#8211;40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig&#39;s rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 &#215; 106 cells) and HA composite (4&#37;) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. Results: The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4&#37; and 25&#37; of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. Conclusion: Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials. 


Human leukocyte antigen-A*33:03-B*58:01-DRB1*15:140, a deduced probable human leukocyte antigen haplotype in association with a human leukocyte antigen low-incidence allele DRB1*15:140 in Taiwanese individuals: A case analysis
Kuo-Liang Yang, Zheng-Zhong Zheng

Tzu Chi Medical Journal 2019 31(1):20-22

Objective: Human leukocyte antigen (HLA)-DRB1&#42;15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1&#42;15:140 and to deduce a probable HLA-DRB1&#42;15:140-associated HLA haplotype in Taiwanese individuals. Materials and Methods: A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer&#39;s protocols. Results: The DNA sequence of HLA-DRB1&#42;15:140 is identical to DRB1&#42;15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1&#42;15:02:01:01 where a G in DRB1&#42;15:02:01:01 is replaced by an A in DRB1&#42;15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1&#42;15:02:01:01 is replaced by an asparagine (N) in DRB1&#42;15:140. We deduced the probable HLA haplotype associated with DRB1&#42;15:140 in Taiwanese to be HLA-A&#42;33:03-B&#42;58:01-DRB1&#42;15:140. Conclusion: Information on the ethnicity and distribution of DRB1&#42;15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele. 


Osteocalcin and carotid–femoral pulse wave velocity in patients on peritoneal dialysis
Po-Jui Chi, Yu-Li Lin, Jen-Pi Tasi, Chih-Hsien Wang, Jia-Sian Hou, Chung-Jen Lee, Bang-Gee Hsu

Tzu Chi Medical Journal 2019 31(1):23-28

Objective: Vascular calcification is a cardiovascular risk factor in dialysis patients. Vascular calcification involves a complex process of biomineralization resembling osteogenesis, which leads to arterial stiffness. Osteocalcin is the most abundant noncollagenous protein in the bone matrix. It is synthesized in the bone by osteoblasts and reflects the rate of bone formation. The aim of this study was to evaluate the relationship between serum osteocalcin levels and the carotid&#8211;femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. Materials and Methods: Serum intact osteocalcin and cfPWV were measured in 62 PD patients. Those with CfPWV values &#62;10 m/s were defined as the high central arterial stiffness group, while those with values &#8804;10 m/s were regarded as the low central arterial stiffness group, according to the European Society of Hypertension and of the European Society of Cardiology guidelines. Results: Seventeen of the 62 PD patients (27.4&#37;) were in the high central arterial stiffness group. The high central arterial stiffness group were older (P &#61; 0.002), had a longer PD vintage (P &#61; 0.018), and had higher serum osteocalcin levels (P &#61; 0.001) than those in the low group. Multivariate logistic regression analysis showed that the osteocalcin level (odds ratio: 1.069, 95&#37; confidence interval (CI): 1.005&#8211;1.137, P &#61; 0.035), PD vintage (odds ratio: 1.028, 95&#37; CI: 1.010&#8211;1.048, P &#61; 0.003), and age (odds ratio: 1.081, 95&#37; CI: 1.005&#8211;1.162, P &#61; 0.035) were independently associated with central arterial stiffness in PD patients. Among these patients, cfPWV (&#961;: 0.216, P &#61; 0.001) values and log-transformed intact parathyroid hormone (&#961;: &#8722;&#39;0.447, P &#60; 0.001) levels were independently associated with the osteocalcin level in PD patients after multivariate forward stepwise linear regression analysis. Conclusion: Older PD patients with a longer PD vintage and higher serum osteocalcin levels had higher central arterial stiffness as measured by cfPWV. The serum osteocalcin level is an independent marker of central arterial stiffness in PD patients. 


Ovo-lactovegetarian diet as a possible protective factor against gallbladder polyps in Taiwan: A cross-sectional study
Hao-Wen Liu, Cheng-Yu Chen

Tzu Chi Medical Journal 2019 31(1):29-34

Objective: Gallbladder polyps (GBPs) are an increasingly common incidental finding and 3&#37; to 8&#37; of GBPs become malignant. A poor prognosis is expected in patients with gallbladder cancer. No studies have considered the relationship between diet and the development of GBPs in the Taiwanese population. The objective of this study was to investigate whether a vegetarian diet protects against GBP development. Materials and Methods: This cross-sectional study included 11,717 individuals who received a health checkup at Taipei Tzu Chi Hospital (New Taipei City, Taiwan) between October 2011 and October 2016. All individuals completed questionnaires that collected data about their characteristics, dietary patterns, and lifestyle. Physical examinations were conducted, and blood chemistry tests were performed. The presence of GBPs was determined using ultrasonography. We subsequently evaluated the association between diet and GBP prevalence using multivariate analysis. Results: The prevalence of GBPs for the entire group was 8.3&#37;. GBPs were significantly less common in the vegetarian groups (vegans 9.0&#37;, ovo-lacto vegetarians 7.5&#37;, and semi-vegetarians 7.2&#37;) compared with the omnivore group (9.6&#37;) (P &#61; 0.002). Step-wise logistic regression revealed that an ovo-lacto vegetarian diet was a possible protective factor (odds ratio &#61; 0.83, P &#61; 0.015). Conclusions: The study findings showed a strong negative association between an ovo-lacto vegetarian diet and GBP occurrence. 


Treatment outcomes for multidrug-resistant tuberculosis in Eastern Taiwan
Chih-Bin Lin, Hung-Chieh Sun, Chen-Yuan Chiang, Che-Wei Wu, Hsu-Wen Chou, Tao-Qian Tang, Jen-Jyh Lee

Tzu Chi Medical Journal 2019 31(1):35-39

Objectives: The objective of this study is to evaluate the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) under special programmatic management in Eastern Taiwan over the past 10 years. Materials and Methods: All newly diagnosed MDR-TB patients and MDR-TB patients enrolled previously with persistent positive cultures were included in this study, from May 2007 to April 2017, in Eastern Taiwan. A panel of pulmonologists designed the initial MDR-TB regimens. Subsequently, regimens were adjusted according to drug susceptibility test results for second-line drugs. Mobile teams were organized for treatment support, and several measures were adapted to safeguard effective treatment support. Results: A total of 178 patients with bacteriological confirmed pulmonary MDR-TB were identified, of whom 167 had treatment outcomes when the study was conducted. Of these 167 patients, 120 (71.9&#37;) were cured, 11 (6.5&#37;) completed therapy (78.4&#37; had successful treatment), 25 (15.0&#37;) died, 9 (5.4&#37;) had treatment failure, none were transferred out, and 2 (1.2&#37;) were lost to follow-up. Surgery was performed on 8 (4.8&#37;). Conclusions: This is an analysis of the treatment outcomes after adopting the Directly Observed Treatment, Short-course Plus program to treat MDR-TB patients in Eastern Taiwan. We had a low proportion of loss-to-follow-up, resulting in a high treatment success rate. This program serves as an effective model in providing quality care to patients with MDR-TB. 


Prognosticators of hepatocellular carcinoma with intrahepatic vascular invasion
Yuan-Chen Lo, Feng-Chun Hsu, Shih-Kai Hung, Kuo-Chih Tseng, Yu-His Hsieh, Moon-Sing Lee, Chih-Wei Tseng, Hon-Yi Lin, Liang-Cheng Chen, Wen-Yen Chiou

Tzu Chi Medical Journal 2019 31(1):40-46

Objective: The prognosis of intrahepatic vascular invasion, including unilateral or main portal vein tumor thrombosis (PVTT) and hepatic vein thrombosis, is still poor. Many patients with intrahepatic vascular invasions never receive radiotherapy (RT). In recent years, more conformal RT techniques such as intensity-modulated RT (IMRT) have been developed and applied to treat other cancers and have significantly improved treatment results and decreased side effects. The purpose of this study is to evaluate the treatment results in patients with intrahepatic vascular invasion and explore the role of IMRT in these treatments. Materials and Methods: There were a total of 73 patients with newly diagnosed AJCC stage IIIB hepatocellular carcinoma (HCC), with either PVTT or hepatic vein tumor thrombosis between 2007 and 2015 in our hospital. IMRT was used for all patients who received RT. Prognostic factors, including treatment modalities, liver function, and comorbidities, were analyzed using univariate and multivariate analysis with the Cox model. Survival time was analyzed using the Kaplan&#8211;Meier method. Results: The longest follow-up time was 45.3 months. The median age was 67 years. Univariate analyses indicated that IMRT, transarterial chemoembolization (TACE), target therapy (sorafenib), tumor size, Child-Pugh class, and ascites were significantly associated with overall survival (OS). In multivariate analysis, IMRT (hazard ratio [HR], 0.495; P &#61; 0.019), sorafenib (HR, 0.340; P &#61; 0.013), tumor size (HR, 2.085; P &#61; 0.020), and Child-Pugh class (P &#61; 0.004), were independent prognostic predictors for patients with intrahepatic vessel invasion, but TACE and ascites were not. The outcomes of patients who had different treatment modalities were significantly different (P &#60; 0.001). Patients who received IMRT with TACE had the best outcomes. Patients who received an RT dose above 5400 cGy had better outcomes than those who with a dose below 5400 cGy, although the results were not significantly different (P &#61; 0.248). Conclusion: IMRT is an important treatment component for patients with intrahepatic vascular invasion. Combined treatment modalities, such as IMRT with TACE, could improve the outcomes of HCC patients with intrahepatic vessel invasion. 


Medium-term clinical outcomes of laminoplasty with adjunct short anterior fusion in multilevel cervical myelopathy
Tsung-Chiao Wu, Kuang-Ting Yeh, Ru-Ping Lee, Tzai-Chiu Yu, Ing-Ho Chen, Cheng-Huan Peng, Kuan-Lin Liu, Jen-Hung Wang, Wen-Tien Wu

Tzu Chi Medical Journal 2019 31(1):47-51

Objectives: Expansive open-door laminoplasty (EOLP) is effective for multilevel cervical spondylotic myelopathy (MCSM). When MCSM is combined with one- or two-level segmental kyphosis, instability, or major anterior foci, EOLP with short-segment anterior cervical fusion (ACF) results in good short-term neurological recovery and can preserve postoperative range of motion (ROM). The objective of this study was to evaluate the medium-term clinical outcomes of this procedure and to analyze the risk factors affecting the neurological function at the last follow-up. Materials and Methods: A total of 87 patients were enrolled in this retrospective study conducted from January 2007 to May 2011. These patients exhibited MCSM with combined short segmental kyphosis, instability, or major anterior pathology, and received EOLP and short-segment anterior fusion. The follow-up period lasted at least 60 months. The radiographic outcomes were collected from plain radiographs with dynamic views checked preoperatively and at the last follow-up. Neurological status and visual analog scale scores for neck pain were evaluated. Logistic regression analysis was then applied to determine the correlation between radiographic parameters and rates of neurological recovery. Results: The mean Japanese Orthopedics Association recovery rate at the last follow-up was 77.8&#37;. The improvement in functional scores and reduction in neck pain were statistically significant. The most influential risk factor affecting neurologic recovery was preoperative functional status. Conclusions: EOLP followed by short-segment ACF is a favorable treatment for patients with MCSM with concomitant short-segment kyphosis, instability, or major anterior pathology. 


Magnetic resonance angiography determined variations in the circle of Willis: Analysis of a large series from a single center
Reddy Ravikanth, Babu Philip

Tzu Chi Medical Journal 2019 31(1):52-59

Objective: The purpose of this study is to evaluate and describe the prevalence and patterns of arterial variants in the circle of Willis (CW) seen in noncontrast three-dimensional time-of-flight magnetic resonance angiography in a series of patients with cerebral vascular accidents (CVAs). Materials and Methods: A descriptive study was undertaken in 200 patients who presented for screening for CVA in the Department of Radiodiagnosis and Imaging, St. John&#39;s Medical College Hospital, Bengaluru, from September 2014 to September 2016. Results: The most common types of CW in a single subject were anterior variant Type A and posterior variant Type E. Type A in the anterior circulation is the normal adult pattern. There is a single anterior communicating artery. The internal carotid artery bifurcates into the precommunicating segment of the anterior cerebral artery and middle cerebral artery. Type E in the posterior circulation is hypoplasia or absence of both posterior communicating arteries and isolation of the anterior and posterior parts of the circle at this level. Overall, CW variants were slightly more common in women than in men. Conclusion: Our findings show that the configuration of the CW may vary greatly in the general population. The wide range in the morphology of CW warrants further research on various races and larger populations to confirm the influence of genetic, regional, environmental, and hemodynamic factors or their combination. 


REVIEW ARTICLES - CLINICAL 

Female genital mutilation; culture, religion, and medicalization, where do we direct our searchlights for it eradication: Nigeria as a case studyp. 1
Olalekan Olugbenga Awolola, NA Ilupeju
DOI:10.4103/tcmj.tcmj_127_18  
Female genital mutilation (FGM) is a form of violence against the girls and the women and also an infringement into the rights of the women in the society. It is practiced mostly in Africa, but migration has revolutionized its spread to almost all parts of the world. The government and the constituted authorities, our traditional rulers, the legislative, the judiciary, and the law enforcement agents have the machineries to stop this inhuman behavior, but they lack the will and the necessary information about the incidence and consequences of FGM. The review involved Internet and literature search mostly those written on the African continent and some that were specific to Nigeria from 1999 to 2018. This article reviewed the spread, the obstetrics and the gynecological complications, the roles of the traditional circumcisers, and the negative and the positive roles of the caregivers, especially its medicalization in the abandonment of FGM in Nigeria. The article also looked critically at the best ways to achieve zero tolerance to FGM. To achieve the targeted zero tolerance to FGM, the identified factors have to be tackled holistically.
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The roles of anti-citrullinated protein antibodies in the immunopathogenesis of rheumatoid arthritisp. 5
Hui-Chun Yu, Ming-Chi Lu
DOI:10.4103/tcmj.tcmj_116_18  
Rheumatoid arthritis (RA) is a common systemic autoimmune disease. Its major manifestation is persistent joint inflammation, which can lead to bone destruction and severe disability. The immunopathogenesis of RA is very complex, involving both innate and adaptive immune systems. Recently, the discovery of anti-citrullinated protein antibodies (ACPAs) has revolutionized the diagnosis and our understanding of the immunopathogenesis of RA. The presence of ACPAs is also closely linked to the disease activity of RA. Therefore, it is reasonable to believe that ACPAs and protein citrullination are key issues for the development of RA. We have summarized the recent study results in this review. The first theory concerning the pathogenesis of RA proposed that ACPAs link the well-known genetic and environmental risk factors for developing RA. However, due to the close association between joint inflammation and ACPAs, a more direct role of ACPAs in the immunopathogenesis of RA is anticipated. Within the past 10 years, many studies, including some of our own, have shown that ACPAs can promote an inflammatory response through complement activation, formation of neutrophil extracellular traps, and direct binding to key players, including monocytes, osteoclasts, and osteoblasts, in the mediation of bone destruction in the joints of RA patients. We also present some new perspectives and issues that need to be further investigated.
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ORIGINAL ARTICLES - BASICTop

Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig modelp. 11
Kun-Chi Wu, Yu-Hsun Chang, Hwan-Wun Liu, Dah-Ching Ding
DOI:10.4103/tcmj.tcmj_87_18  
Objectives: Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. Materials and Methods: The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC–HA coculture. Two healthy female minipigs weighing 30–40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig's rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 × 106 cells) and HA composite (4%) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. Results: The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4% and 25% of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. Conclusion: Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials.
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Human leukocyte antigen-A*33:03-B*58:01-DRB1*15:140, a deduced probable human leukocyte antigen haplotype in association with a human leukocyte antigen low-incidence allele DRB1*15:140 in Taiwanese individuals: A case analysisp. 20
Kuo-Liang Yang, Zheng-Zhong Zheng
DOI:10.4103/tcmj.tcmj_72_18  
Objective: Human leukocyte antigen (HLA)-DRB1*15:140 is a low-frequency allele in the HLA-DRB1 locus. The aim of this study is to confirm the ethnicity of DRB1*15:140 and to deduce a probable HLA-DRB1*15:140-associated HLA haplotype in Taiwanese individuals. Materials and Methods: A total of 1815 healthy unrelated Taiwanese individuals and 14,562 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exons 1 and 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. Results: The DNA sequence of HLA-DRB1*15:140 is identical to DRB1*15:02:01:01 in exons 1 and 2, except at residue 91 of DRB1*15:02:01:01 where a G in DRB1*15:02:01:01 is replaced by an A in DRB1*15:140 (codon 2; GAC->AAC). The nucleotide substitution in exon 1 introduces a one amino acid substitution at residue 2 where an aspartic acid (D) in DRB1*15:02:01:01 is replaced by an asparagine (N) in DRB1*15:140. We deduced the probable HLA haplotype associated with DRB1*15:140 in Taiwanese to be HLA-A*33:03-B*58:01-DRB1*15:140. Conclusion: Information on the ethnicity and distribution of DRB1*15:140 and its deduced probable HLA haplotype in association with the low-incidence allele is of value for HLA-testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.
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ORIGINAL ARTICLES - CLINICAL RESEARCHTop

Osteocalcin and carotid–femoral pulse wave velocity in patients on peritoneal dialysisp. 23
Po-Jui Chi, Yu-Li Lin, Jen-Pi Tasi, Chih-Hsien Wang, Jia-Sian Hou, Chung-Jen Lee, Bang-Gee Hsu
DOI:10.4103/tcmj.tcmj_12_18  
Objective: Vascular calcification is a cardiovascular risk factor in dialysis patients. Vascular calcification involves a complex process of biomineralization resembling osteogenesis, which leads to arterial stiffness. Osteocalcin is the most abundant noncollagenous protein in the bone matrix. It is synthesized in the bone by osteoblasts and reflects the rate of bone formation. The aim of this study was to evaluate the relationship between serum osteocalcin levels and the carotid–femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. Materials and Methods: Serum intact osteocalcin and cfPWV were measured in 62 PD patients. Those with CfPWV values >10 m/s were defined as the high central arterial stiffness group, while those with values ≤10 m/s were regarded as the low central arterial stiffness group, according to the European Society of Hypertension and of the European Society of Cardiology guidelines. Results: Seventeen of the 62 PD patients (27.4%) were in the high central arterial stiffness group. The high central arterial stiffness group were older (P = 0.002), had a longer PD vintage (P = 0.018), and had higher serum osteocalcin levels (P = 0.001) than those in the low group. Multivariate logistic regression analysis showed that the osteocalcin level (odds ratio: 1.069, 95% confidence interval (CI): 1.005–1.137, P = 0.035), PD vintage (odds ratio: 1.028, 95% CI: 1.010–1.048, P = 0.003), and age (odds ratio: 1.081, 95% CI: 1.005–1.162, P = 0.035) were independently associated with central arterial stiffness in PD patients. Among these patients, cfPWV (ρ: 0.216, P = 0.001) values and log-transformed intact parathyroid hormone (ρ: −'0.447, P < 0.001) levels were independently associated with the osteocalcin level in PD patients after multivariate forward stepwise linear regression analysis. Conclusion: Older PD patients with a longer PD vintage and higher serum osteocalcin levels had higher central arterial stiffness as measured by cfPWV. The serum osteocalcin level is an independent marker of central arterial stiffness in PD patients.
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Ovo-lactovegetarian diet as a possible protective factor against gallbladder polyps in Taiwan: A cross-sectional studyp. 29
Hao-Wen Liu, Cheng-Yu Chen
DOI:10.4103/tcmj.tcmj_16_18  
Objective: Gallbladder polyps (GBPs) are an increasingly common incidental finding and 3% to 8% of GBPs become malignant. A poor prognosis is expected in patients with gallbladder cancer. No studies have considered the relationship between diet and the development of GBPs in the Taiwanese population. The objective of this study was to investigate whether a vegetarian diet protects against GBP development. Materials and Methods:This cross-sectional study included 11,717 individuals who received a health checkup at Taipei Tzu Chi Hospital (New Taipei City, Taiwan) between October 2011 and October 2016. All individuals completed questionnaires that collected data about their characteristics, dietary patterns, and lifestyle. Physical examinations were conducted, and blood chemistry tests were performed. The presence of GBPs was determined using ultrasonography. We subsequently evaluated the association between diet and GBP prevalence using multivariate analysis. Results:The prevalence of GBPs for the entire group was 8.3%. GBPs were significantly less common in the vegetarian groups (vegans 9.0%, ovo-lacto vegetarians 7.5%, and semi-vegetarians 7.2%) compared with the omnivore group (9.6%) (P = 0.002). Step-wise logistic regression revealed that an ovo-lacto vegetarian diet was a possible protective factor (odds ratio = 0.83, P = 0.015). Conclusions: The study findings showed a strong negative association between an ovo-lacto vegetarian diet and GBP occurrence.
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Treatment outcomes for multidrug-resistant tuberculosis in Eastern Taiwanp. 35
Chih-Bin Lin, Hung-Chieh Sun, Chen-Yuan Chiang, Che-Wei Wu, Hsu-Wen Chou, Tao-Qian Tang, Jen-Jyh Lee
DOI:10.4103/tcmj.tcmj_18_18  
Objectives: The objective of this study is to evaluate the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) under special programmatic management in Eastern Taiwan over the past 10 years. Materials and Methods: All newly diagnosed MDR-TB patients and MDR-TB patients enrolled previously with persistent positive cultures were included in this study, from May 2007 to April 2017, in Eastern Taiwan. A panel of pulmonologists designed the initial MDR-TB regimens. Subsequently, regimens were adjusted according to drug susceptibility test results for second-line drugs. Mobile teams were organized for treatment support, and several measures were adapted to safeguard effective treatment support. Results: A total of 178 patients with bacteriological confirmed pulmonary MDR-TB were identified, of whom 167 had treatment outcomes when the study was conducted. Of these 167 patients, 120 (71.9%) were cured, 11 (6.5%) completed therapy (78.4% had successful treatment), 25 (15.0%) died, 9 (5.4%) had treatment failure, none were transferred out, and 2 (1.2%) were lost to follow-up. Surgery was performed on 8 (4.8%). Conclusions: This is an analysis of the treatment outcomes after adopting the Directly Observed Treatment, Short-course Plus program to treat MDR-TB patients in Eastern Taiwan. We had a low proportion of loss-to-follow-up, resulting in a high treatment success rate. This program serves as an effective model in providing quality care to patients with MDR-TB.
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Prognosticators of hepatocellular carcinoma with intrahepatic vascular invasionp. 40
Yuan-Chen Lo, Feng-Chun Hsu, Shih-Kai Hung, Kuo-Chih Tseng, Yu-His Hsieh, Moon-Sing Lee, Chih-Wei Tseng, Hon-Yi Lin, Liang-Cheng Chen, Wen-Yen Chiou
DOI:10.4103/tcmj.tcmj_14_18  
Objective: The prognosis of intrahepatic vascular invasion, including unilateral or main portal vein tumor thrombosis (PVTT) and hepatic vein thrombosis, is still poor. Many patients with intrahepatic vascular invasions never receive radiotherapy (RT). In recent years, more conformal RT techniques such as intensity-modulated RT (IMRT) have been developed and applied to treat other cancers and have significantly improved treatment results and decreased side effects. The purpose of this study is to evaluate the treatment results in patients with intrahepatic vascular invasion and explore the role of IMRT in these treatments. Materials and Methods: There were a total of 73 patients with newly diagnosed AJCC stage IIIB hepatocellular carcinoma (HCC), with either PVTT or hepatic vein tumor thrombosis between 2007 and 2015 in our hospital. IMRT was used for all patients who received RT. Prognostic factors, including treatment modalities, liver function, and comorbidities, were analyzed using univariate and multivariate analysis with the Cox model. Survival time was analyzed using the Kaplan–Meier method. Results: The longest follow-up time was 45.3 months. The median age was 67 years. Univariate analyses indicated that IMRT, transarterial chemoembolization (TACE), target therapy (sorafenib), tumor size, Child-Pugh class, and ascites were significantly associated with overall survival (OS). In multivariate analysis, IMRT (hazard ratio [HR], 0.495; P = 0.019), sorafenib (HR, 0.340; P = 0.013), tumor size (HR, 2.085; P= 0.020), and Child-Pugh class (P = 0.004), were independent prognostic predictors for patients with intrahepatic vessel invasion, but TACE and ascites were not. The outcomes of patients who had different treatment modalities were significantly different (P < 0.001). Patients who received IMRT with TACE had the best outcomes. Patients who received an RT dose above 5400 cGy had better outcomes than those who with a dose below 5400 cGy, although the results were not significantly different (P = 0.248). Conclusion: IMRT is an important treatment component for patients with intrahepatic vascular invasion. Combined treatment modalities, such as IMRT with TACE, could improve the outcomes of HCC patients with intrahepatic vessel invasion.
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Medium-term clinical outcomes of laminoplasty with adjunct short anterior fusion in multilevel cervical myelopathyp. 47
Tsung-Chiao Wu, Kuang-Ting Yeh, Ru-Ping Lee, Tzai-Chiu Yu, Ing-Ho Chen, Cheng-Huan Peng, Kuan-Lin Liu, Jen-Hung Wang, Wen-Tien Wu
DOI:10.4103/tcmj.tcmj_22_18  
Objectives: Expansive open-door laminoplasty (EOLP) is effective for multilevel cervical spondylotic myelopathy (MCSM). When MCSM is combined with one- or two-level segmental kyphosis, instability, or major anterior foci, EOLP with short-segment anterior cervical fusion (ACF) results in good short-term neurological recovery and can preserve postoperative range of motion (ROM). The objective of this study was to evaluate the medium-term clinical outcomes of this procedure and to analyze the risk factors affecting the neurological function at the last follow-up. Materials and Methods: A total of 87 patients were enrolled in this retrospective study conducted from January 2007 to May 2011. These patients exhibited MCSM with combined short segmental kyphosis, instability, or major anterior pathology, and received EOLP and short-segment anterior fusion. The follow-up period lasted at least 60 months. The radiographic outcomes were collected from plain radiographs with dynamic views checked preoperatively and at the last follow-up. Neurological status and visual analog scale scores for neck pain were evaluated. Logistic regression analysis was then applied to determine the correlation between radiographic parameters and rates of neurological recovery. Results: The mean Japanese Orthopedics Association recovery rate at the last follow-up was 77.8%. The improvement in functional scores and reduction in neck pain were statistically significant. The most influential risk factor affecting neurologic recovery was preoperative functional status. Conclusions: EOLP followed by short-segment ACF is a favorable treatment for patients with MCSM with concomitant short-segment kyphosis, instability, or major anterior pathology.
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Magnetic resonance angiography determined variations in the circle of Willis: Analysis of a large series from a single centerp. 52
Reddy Ravikanth, Babu Philip
DOI:10.4103/tcmj.tcmj_167_17  
Objective: The purpose of this study is to evaluate and describe the prevalence and patterns of arterial variants in the circle of Willis (CW) seen in noncontrast three-dimensional time-of-flight magnetic resonance angiography in a series of patients with cerebral vascular accidents (CVAs). Materials and Methods: A descriptive study was undertaken in 200 patients who presented for screening for CVA in the Department of Radiodiagnosis and Imaging, St. John's Medical College Hospital, Bengaluru, from September 2014 to September 2016. Results:The most common types of CW in a single subject were anterior variant Type A and posterior variant Type E. Type A in the anterior circulation is the normal adult pattern. There is a single anterior communicating artery. The internal carotid artery bifurcates into the precommunicating segment of the anterior cerebral artery and middle cerebral artery. Type E in the posterior circulation is hypoplasia or absence of both posterior communicating arteries and isolation of the anterior and posterior parts of the circle at this level. Overall, CW variants were slightly more common in women than in men. Conclusion: Our findings show that the configuration of the CW may vary greatly in the general population. The wide range in the morphology of CW warrants further research on various races and larger populations to confirm the influence of genetic, regional, environmental, and hemodynamic factors or their combination.
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CASE REPORTSTop

Janus kinase 2 V617F mutation in an unrelated peripheral blood stem cell donorp. 60
Shang-Hsien Yang, Hsiang-Lin Wan, Ming-Hui Gu, Tso-Fu Wang
DOI:10.4103/tcmj.tcmj_189_17  
Polycythemia vera (PV) is relatively uncommon in early adulthood, and evidence about the prevalence of the Janus kinase 2 (JAK2) V617F mutation in the general population is limited. Here, we report a previously healthy volunteer peripheral blood stem cell (PBSC) donor who developed symptomatic PV with the JAK2 V617F mutation 2 years after PBSC mobilization and harvest. The characteristic mutation was identified retrospectively in the blood sample of the donor at the confirmation typing stage, which was before granulocyte colony-stimulating factor injection. This report presents a safety issue for both donor and recipient of hematopoietic stem cell transplantation. Clinicians should be aware of this during health workup and postdonation follow-up of unrelated PBSC donors. Any abnormal and/or equivocal laboratory data, especially during the donor workup stage, should not be overlooked.
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A rare case of septic cavernous sinus thrombosis as a complication of sphenoid sinusitisp. 63
Ming-Chun Chen, Yu-Huai Ho, Pau-Nyen Chong, Jui-Hsia Chen
DOI:10.4103/tcmj.tcmj_1_18  
Isolated sphenoid sinusitis is a rare disorder and may present with severe complications due to its proximity to the orbital and intracranial areas. We report a 13-year-old boy hospitalized for septic shock with fever of unknown origin. Facial palsy was later noted. Brain magnetic resonance imaging showed a sphenoid mass and right cavernous sinus and internal jugular vein thrombosis. Biopsy revealed chronic rhinosinusitis. Complete recovery followed by an incision/drainage procedure and antibiotic treatment. Acute sphenoid sinusitis should be included in the differential diagnosis of septic manifestations mimicking central nervous system infection or cranial nerve palsy.
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LETTER TO THE EDITORTop

Dengue fever with chikungunya concurrent infectionp. 66
Pathum Sookaromdee, Viroj Wiwanitkit
DOI:10.4103/tcmj.tcmj_121_18  
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