Tehran University Medical Journal

RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer: a review article

Safura Pakizehkar

Medullary thyroid cancer accounts for 5-10% of thyroid carcinomas. RET proto-oncogene mutations occur in all of the hereditary MTCs and about 66% of the sporadic MTCs. So, the detection of the RET mutations is necessary for rapid and proper diagnosis and treatment. This systematic review seeks to find a comprehensive list of RET gene mutations in the diagnosis of medullary thyroid cancer.
The previous studies on RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer were searched in the major databases including PubMed, Scopus, Medline, Embase and NCBI between 2010 and 2021.
Missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene have the highest frequency in MTCs. The most common mutations in FMTC, are in codons 609, 611, 618, and 620 in exon 10, codon 768 in exon 13, codon 804 in exon 14, and codon 634 in exon 11. In the case of MEN2A, RET gene mutations have been observed in exons 5, 8, 10, 11, with the highest mutations in exons 10 (codons 609, 611, 618, and 620) and exon 11 (codons 630 and 634). Moreover, M918T mutation in exon 16 and A883F mutation in exon 15 have been detected in 95% and 5% of the patients with MEN2B respectively. In the case of MTC, the M918T mutation in exon 16 is the most common mutation, which is associated with a poor prognosis. RET genetic screening is crucial for an exact approach to the diagnosis and treatment of MTC. Anyone with MTC, even without a family history of MEN2, should be genetically tested for the RET mutations to confirm or rule out the inherited disease and, if necessary, preventive thyroidectomy. This systematic review provided a comprehensive list of the reported mutations in the RET gene for the diagnosis of medullary thyroid cancer.

Study of knee range of motion after soft tissue repair in both flexion and extension during total knee arthroplasty: a randomized clinical trial

Mehdi Raei

Background: The patient's position during the recovery time after arthroplasty surgery can be a factor in reducing complications and improving patients’ condition. Therefore, this study was performed to compare the knee range of motion after soft tissue repair in both flexion and extension positions of total knee arthroplasty.
Methods: This study is a double-blind clinical trial. The study population was all candidates for total knee arthroplasty surgery in Al-Zahra and Kashani hospitals in Isfahan from July 2011 to September 2012. The sample size was selected using the statistical formula of 88 patients and randomly divided into two groups of flexion and extension. In the first group during the knee soft tissue repair, the knee was in flexion and in the second group it was in extension and then it was repaired. Information such as age, sex, body mass index and surgical position were recorded in the checklist. The knee range of motion was measured at the end of the first, second, fourth, eighth and twelfth weeks and recorded in a checklist. In order to compare the pattern of changes in mean knee range of motion over time in the two groups, mixed linear models and conventional marginal models to generalized estimator equations were used by STATA software.

Results: The results showed that there was no significant difference between the flexion and extension groups in knee range of motion. In both groups, the mean knee range of motion increased with time (P<0.001). The mean scores of knee function after the end of the twelfth week in the flexion and extension groups were 141.04±23.19 and 143.09±22.34, respectively, and this difference was not significant.
Conclusion: Soft tissue repair in a particular position is not so effective on the outcome that we want to institutionalize it by spending a considerable amount of budget for training surgeons.

Evaluation role of beta-2 adrenoceptor agonist and antagonist in the expression of gap junction genes (connexin 37/43) in cumulus cells of women with poor ovarian response

Farideh Zafari Zangeneh

Background: Connexon is a membrane structural protein in the gap junctions. These cellular connections are responsible for transporting ions and messenger molecules to the oocyte. This study aimed to investigate the role of beta-2-adrenoceptors in the process of follicle growth based on the expression of the two connexins 37/43 in the gap junctions that have a primary role in the mitotic resumption and oocyte maturation.
Methods: This case-control study was conducted from April 2019 to November 2020 at the Reproductive Health Research Center of Tehran Imam Khomeini Hospital was performed on women with the poor ovarian response (POR) and control (women donate eggs) groups. Both groups had entry criteria with a body mass index under 28 m²/kg and 20-45 years old. Exit criteria were including no drug use except ovarian stimulants and no illness. The diagnosis was made agreeing to the Bologna model criterion. Ovulation stimulation cycle was performed, and then after the puncture, cumulus cells were isolated by enzyme and were freezing in -80 centigrade until the time of inserting into the cell culture medium. Isoproterenol (agonist) and propranolol (antagonist) at a concentration of 100 nM were added to the culture medium as the beta-2 adrenoceptors selective drugs. After culture, RNA extraction was performed and the concentration was read by Nanodrop, and then cDNA was synthesized. Gene expression was determined by real-time PCR.

Results: The findings of connexin expression in the three study groups: without the drug (P<0.001), propranolol (P<0.001), and isoproterenol (P<0.001) were significant compared to the control group. Isoproterenol decreased expression but propranolol increased it (P<0.001).
Conclusion: These findings confirm the important role of connexins 37 and 43 in cumulus cleft junctions that propranolol was able to increase its expression. Therefore, we suggest firstly these two connexins can be an effective target for oocyte growth and maturation. Secondly, propranolol could be a new treatment for women with POR and be effective in assisted reproductive technology (ART).

The prediction of lymphedema via the combination of the selected data mining algorithms

Peiman Bayat

Background: Breast cancer is the second leading cause of cancer death in women, after lung cancer. Due to the importance of predicting this disease, the use of data mining methods in medical research is more significant than before. Data mining algorithms can be a great help in preventing the development of lymphedema in patients. The aim Of this study was to create a diagnosis system that can predict the probability of lymphedema in breast cancer patients.
Methods: In the present study, the factors of lymphedema in 1117 patients with breast cancer have been collected. The likelihood of developing lymphedema is predicted using ensemble learning via 5 heterogeneous classification algorithms, feature selection and the genetic algorithm (The Two-layer Ensemble Feature Selection method). After collecting the data of patients with breast cancer from 2009 to 2018, and data preprocessing using the optimized ensemble learning algorithm and feature selection, we will examine the likelihood of developing lymphedema for the new patient. Finally, the factors affecting the disease have been extracted. Excluding the time of collecting statistical data, the period of the study was from September 2019 to February 2021. This study is performed at Seyed Khandan Rehabilitation Center, Tehran, Iran.
Results: The results of algorithms showed that the accuracy of the ensemble learning method with selected classification algorithms (SVM with RBF kernel) is 87% and the accuracy of the ensemble learning with feature selection method is 90%. According to the final evaluation of the proposed method, the most effective risk factors for lymphedema have been extracted.
Conclusion: Unfortunately, treatment and diagnosis are not without complications, and one of the most important of these complications in breast cancer is lymphedema in the upper extremities, which can affect the quality of life in patients. It is essential to have a method that can accurately suggest to a specialist whether a new patient will develop lymphedema in the future or how likely it is to develop it, using patient’s own clinical and demographic characteristics.

Assessing the role of enema in improving outcomes and complications of benign gynecological laparoscopy: a randomized clinical trial

Azam Barkhordarinasab

Background: mechanical bowel preparation (MBP) is a common practice before laparoscopic gynecologic surgeries but the role and efficacy of preparation have been questioned. this study assesses visualization and bowel handling in a group of patients who receive MBP and the control group and thereafter; compares the results.
Methods: We designed and conducted this randomized, single-blinded and controlled trial on patients who underwent advanced gynecologic laparoscopic surgeries. This clinical trial was carried out between July 2020 and January 2021. The patients were enrolled from l the laparoscopic office. 120 women aged 18-65 years undergoing level 2 and 3 benign gynecologic laparoscopic surgeries were randomized to bowel preparation with a normal saline enema (n=60) or non-bowel preparation (n=60) groups. Our patients underwent level 2 and 3 of benign laparoscopic gynecologic surgeries with or without MBP. The visualization and bowel handling were assessed by the primary surgical team and a questionnaire was later obtained. The outcomes included intraoperative surgical view and bowel handling, preoperative and post-operative patient signs and symptoms. The patients were also assessed in respect to discomfort prior and after the surgery, this assessment was obtained using a questionnaire. The gathered data was analyzed using IBM’s SPSS v26 software.

Results: there was no difference in intraoperative visualization and bowel handling between the two groups. We also found no clinical improvements in respect to discomfort and symptoms. MBP even increased the distention rate amongst patients (P-value=0/04). We tried to evaluate whether MBP had any effects on haemorrhage and blood loss during the surgery and to assess this we compared hemoglobin levels before and after the surgery. We compared the subtracted values between the two groups and found no significant difference (T-test=1.135, P=0/259) (see table 4). However, hospitalization duration was about 5 hours longer in the group who received MBP.
Conclusion: MBP with normal saline enema does not improve intraoperative visualization and bowel handling. And it also does not reduce patient complication rates and post-operative symptoms either. MBP also increases hospitalization duration and puts extra pressure on the healthcare system. Therefore, a normal saline enema is not recommended before benign gynecologic laparoscopic surgeries.

Evaluation of immunogenicity of recombinant influenza nucleoprotein (NP) for universal vaccine

Mohammadreza Zolfaghari

Background: Influenza vaccines based on conserved proteins are being developed persistently. The conserved protein vaccines based on Nucleoprotein (NP) are highly protected vaccines against influenza viruses that can be used as a Universal vaccine. Aluminum hydroxide (Alum) is the most common adjuvant used in vaccine formulation to improve immunization by altering the epitopes’ folds. However, due to its toxic effects on the nervous system, especially in infants and young children exposed to multiple vaccine injections during brain development, it is better to use more desirable options such as carbohydrate-based adjuvants. Sucrose ester (SE) is a carbohydrate and non-ionic surfactant that is compatible with the human body and environmentally friendly. This study evaluated the immunogenicity of recombinant NP molecule prepared in a prokaryotic with the accompaniment of sucrose ester adjuvant against lethal influenza virus challenge in a Balb/c mice model.
Methods: The recombinant vector of PET-28a-NP was used to produce NP molecule. The vaccines containing an NP with or without Alum or sucrose ester adjuvants were injected into the mice. The Effectiveness and immunogenicity were examined by evaluating the humeral immunity induction by Immunoglobulin G (IgG), and its subunits production, and cellular immunity induction by Interferon-Gamma (IFN-γ) and Interleukin-4 (IL-4) production by ELISA Method and also animal’s surveillance was documented. The study took part at the Influenza and other respiratory viruses department of Pasteur institute of Iran in November 2018.
Results: The animals’ surveillance in the Np group was 57.1%, NP+SE was (71.4%), and NP+SE was 64.28%. Also, IgG and its subunits, IL4, and IFN-γ production in both Alum and SE combined vaccines compared to NP alone were significant.

Conclusion: In combination with the carbohydrate adjuvant containing sucrose ester compared to the formulation with alum adjuvant, the NP could provide proper and considerable protection and immunity against the homologous strain (H1N1) of the Influenza A virus. It is recommended that SE usage as an adjuvant results in an adequate immune response and less toxic effect.

Comparison of the analgesic effect before and after injection of hyaluronic acid in patients with knee osteoarthritis in Amir A'alam hospital

Mehdi Sanatkar

Background: One of the most important issues for patients with osteoarthritis is reducing pain and returning them to normal life. In addition to losing weight and improving daily activities, pain management treatments may be needed. One of these treatments is the injection of hyaluronic acid gel into the knee joint, which has been studied in this study.

Methods: In this study, 61 patients with knee osteoarthritis were included and the Then, they received the injection of hyaluronic acid gel, and the intensity of pain, range of motion of the knee joint, and inflammation of the knee joint were measured. The numeric rating scale was used to measure pain intensity, and movement angle was used to measure the range of motion
Results: The mean age of patients in this study was 60.52±11.77 years. Pre-injection pain index in patients was 7.90±0.99, which decreased to 5.49±1.91 on the third day, 5.98±1.98 on the seventh day and 3.77±2.91 on the 30th day (P<0.001). The amplitude of painless movement based on the degree before injection in patients was 38.85±19.44 which increased to 60.25±21.65 on the third day to 65.25±22.65 on the seventh day and to 71.07±24.17 on the 30th day (P<0.001). Inflammation rate was reported before injection in 29 patients which decreased to 6 patients on the third day after injection (P=0.009).
Conclusion: Injection of hyaluronic acid into the joint has analgesic effects and significantly improves the function and range of motion of patients. It is recommended that hyaluronic acid could be considered as a suitable drug in the treatment process of these patients. Considering that using this method, which is a useful treatment method in reducing patients' pain and improving their function, we recommend this method, especially in the elderly and without the need for surgery.

Bartholin gland cancer in a young woman: a case report

Leila Pourali

Background: With 6,020 new cases and 1,150 deaths annually in the United States, vulvar cancer is uncommon, resulting in age-adjusted incidence rates of 2.8 and 1.7 per 100,000 in white and black women, respectively. Vulvar cancer represents about 4% to 6% of malignancies of the female genital tract and 0.6% of all cancers in women. Vulvar cancer predominantly affects postmenopausal women, and it is the most common anogenital cancer in women with more than 70 years of age. HPV infection is associated with a significant number of vulvar cancers. Bartholin Gland carcinoma is a rare form of vulvar malignancy that accounts for less than 5% of all vulvar cancers and 0.001% of all genital cancers. The aim of this study was to report a rare case of Bartholin's cancer in a young patient.
Case Report: The patient was a 37-year-old woman p2l2 (history of two pregnancy and two delivery) who had complains of severe pain in perineal area and was referred to the gynecology emergency clinic, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran, in June 2020. In past medical history she had no previous history of medical illnesses or surgical interventions. She had swelling and pain in perineal area since one year ago. Bartholin Gland abscess was diagnosed and she received some oral antibiotics, but did not improve. On the last examination under anesthesia, a firm mass of about 3 cm was palpated in the third distal part of posterior vagina which was at the site of Bartholin Gland and was necrotic. The pathologic report of the mass biopsy confirmed the diagnosis of squamous cell carcinoma. The patient was underwent chemo radiation therapy. At a follow up visit about 5 month later she was cured completely and there was not any symptom of recurrence or metastasis.
Conclusion: In dealing with any patient with diagnosis of Bartholin Gland abscess, in the case of resistance to medical treatment, further evaluation and biopsy of the mass should be considered to rule out Bartholin's gland cancer.

Persistent hiccups as an atypical presentation of covid-19: a brief report

Hosein Pormasoumi

Background: coronavirus disease (COVID-19) as an emerging infectious disease started in China in 2019. By increasing the number of patients and spreading to all countries, it was considered a pandemic disease. COVID-19 became an international concern. Patients affected by coronavirus (SARS-Cov-2) reported different symptoms. Most signs and symptoms were related to the respiratory system. To our knowledge, the onset of Covid-19 with chronic hiccups was reported in two patients. The aim of this study was to assess the onset of symptoms of Covid-19 disease in patients in a hospital in Zabol, Iran.
Methods: This study is a retrospective descriptive cross-sectional study which was performed from March to June 2021. The study setting was a hospital affiliated with Zabol Medical University. The study population included all patients diagnosed with Covid-19. A total of 350 patients were selected by the census. For data gathering, we used Patient’s records including demographic information, clinical examination records, and para-clinical tests results. We used descriptive statistics and SPSS ver. 20 for data analysis and management.

Results: A total of 350 patients were diagnosed with Covid-19. The number of 232 (66.28%) patients were hospitalized for receiving hospital care. 118(33.72%) were recommended to stay at home and receive care. Inpatients included 119(51.29%) male and 113(48.71%) female. The mean age of patients was 41.75(±15.6) years. The main complaint of 349(99.71%) patients was respiratory problems. A 44-year-old male patient with a history of 8 years of diabetes had chronic hiccups.
Conclusion: according to our findings, unexpected signs and symptoms should be considered during the pandemic event. By identifying different symptoms of the disease, the provision of health services from diagnosis to care and treatment is improved. Since Covid-19 disease is an emerging disease and all its dimensions have not been identified yet, a thorough examination of patients who are referred to medical centers can help identify and reporting different cases.

Comparison of ureteral opening distance from midline in children with vesicoureteral reflux and healthy children: a brief report

Fatemeh Karami Robati

Background: Vesicoureteral reflux (urinary reflux) is one of the most common congenital anomalies in children. This study aimed to compare the ureteral opening distance from the midline in children with vesicoureteral reflux (VUR) and healthy children
Methods: This cross-sectional study was performed on the children with pyelonephritis who were referred to Afzalipour Hospital in Kerman, Iran from August 2019 to August 2020. Twenty children with vesicoureteral reflux (urinary reflux) and twenty healthy children were randomly selected. Then children with vesicoureteral reflux (urinary reflux) and healthy children were divided into two groups. The distance from the ureter to the midline in these children was then measured by a radiologist with a Philips affinity 70 ultrasound machine.

Results: In both groups (healthy children and ones with vesicoureteral reflux), ninety-five percent of the children were girls. The mean age of the children in the second group (the children with urinary reflux) was 5.8±2.58 years and the mean age of the children in the first group (the healthy children) was 4.75±1.54 years. The mean age difference between the children with urinary reflux and healthy children was not statistically significant (P=0.127). The mean distance of the ureter from the midline in children with vesicoureteral reflux was 11.44±2.60 mm and the mean distance of the ureter from the midline in healthy children was 9.32±2.74 mm. The mean difference distance of the ureter from the midline in children with vesicoureteral reflux (VUR) and healthy children was statistically significant (P=0.002).
Conclusion: Considering that the distance between the ureter and the midline in patients with urinary reflux is significantly longer than non-reflux ureters, it can be used as a non-invasive method for the diagnosis of vesicoureteral reflux (urinary reflux) in children.

Rethinking mental health policy-making in Iran: a letter to the editor

Ahmad Ali Noorbala