Variable presentations of six conjunctival/limbal ocular surface squamous neoplasia (OSSN) cases: How good is our clinical judgment evidenced by the correlation to the histopathological findings and diagnosis?

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) may have atypical or unusual presentations and may attain large sizes especially in cases of delayed presentation resulting in late diagnosis, treatment, and eventual guarded visual prognosis. We are reporting an interesting cases series of OSSN with variable clinical presentations to highlight the importance of the pre-operative clinical judgment and tissue diagnosis. PRESENTATION OF CASES: Six patients (4 females and 2 males; mean age 59 years; range 42-79 years) were included with suspicious conjunctival lesions. The maximum dimension of the lesions was 17 mm. The initial suspected pre-operative clinical diagnosis -other than OSSN- included pterygium/pinguecula (n = 2), benign squamous papilloma (n = 1), cyst versus pyogenic granuloma (n = 1), and lymphoma (n = 1). This work has been reported in line with the PROCESS criteria. DISCUSSION: The final histopathological diagnosis was unexpectedly invasive squamous cell carcinoma (SCC) in 4, one SCC in-situ, and squamous dysplasia in one. The primary treatment included MMC 0.02 % for 2 cycles for chemo-reduction in one of the cases where OSSN was suspected. Excisional biopsy was performed eventually for all lesions with application of one or more of the following modalities: MMC 0.02 %, absolute alcohol 99 %, and cryotherapy to the conjunctival margin. No tumor recurrence was noted in any of the patients after an average period of follow-up of 26 months. Even though the outcome was good, tumor-related morbidity and delay in the referral by general ophthalmologists are to be considered. CONCLUSION: Conjunctival OSSN has wide presentation clinically and can be challenging in terms of diagnosis. Histopathological evaluation is essential for a definitive diagnosis and treatment. Accurate clinical diagnosis might affect the management plan with consideration for topical therapeutic modalities, however, these cases are best managed by wide excision using the no-touch technique and double-freeze-thaw cryotherapy to the conjunctiva with consideration of topical chemotherapy.

Pediatricians' Awareness of Pediatric Psoriasis in the Makkah Region, Saudi Arabia.

Background Psoriasis is an autoimmune disease characterized by the typical appearance of red, thickened, scaly patches on the skin (plaques). These plaques can vary in size and distribution from person to person. In some individuals, it may affect small areas of skin, while in others, large areas covering their body may be involved. Patients with psoriasis might be identified by pediatricians before being seen by dermatologists, highlighting the need for pediatricians to be aware and knowledgeable about pediatric psoriasis. Objective To evaluate the knowledge and management of pediatric psoriasis among pediatricians and pediatric residents in the Makkah region, Saudi Arabia. Methods This was a cross-sectional study using a questionnaire targeted at pediatricians. It inquired about sociodemographic details, knowledge of psoriasis risk factors, diagnosis, management, comorbidity screening, and indications for consulting a dermatologist. The knowledge score cut-off was set at 60%, with scores below this threshold considered indicative of poor knowledge and scores above it reflecting good knowledge. Results A total of 139 participants completed the questionnaire; 103 (74.1%) were from Jeddah, 101 (72.7%) were pediatric residents, 118 (84.9%) were general pediatricians, and 18 (15.1%) were in subspecialties. About a third, 49 (35.3%), reported having seen a child with psoriasis. Most participants, 84 (60.4%), had a good knowledge level regarding psoriasis. The vast majority, 119 (85.6%), stated that topical therapies are the first-line treatment; 105 (75.5%) reported being confident in diagnosing psoriasis, and having previously seen a patient with psoriasis was associated with certainty in diagnosis (p-value=0.048); 82 (59%) referred patients to dermatologists. Physician position (p-value=0.049) and being in a general specialty (p-value=0.048) were associated with higher knowledge. Conclusion Overall, participants had good knowledge of pediatric psoriasis and its management. However, there is still a need for improvement.

Knowledge of and attitude toward attention-deficit/ hyperactivity disorder (ADHD) assessed among primary schoolteachers of Makkah City in Saudi Arabia.

Background: One of the most prevalent pediatric medical conditions is attention-deficit/hyperactivity disorder (ADHD). It is characterized by symptoms of hyperactivity, impulsivity, and/or inattention. The first people to notice a child's ADHD symptoms are typically their teachers, who may then offer data that are typically helpful in its diagnosis. The purpose of this study was to assess teachers' knowledge of ADHD, its causes and etiology, as well as the key demographic factors that influence said knowledge. Method: The study was conducted among schoolteachers of primary schools located in different regions of Makkah City, Kingdom of Saudi Arabia. We used a stratified random sampling technique to collect our sample, with the inclusion criteria being teachers who were working in a primary school and who were directly involved in teaching students. Data analysis was performed using the IBM SPSS Statistics software version 21. Results: We received 335 responses to our questionnaire. The age of the participants ranged from 18 to 59 years, with the mean age being 40.2 ± 13.8 years. About 66.9% of teachers were women. Most of the teachers in this sample had a bachelor's degree (73.4%), and only 21.8% had diplomas. Regarding the years of teaching experience, 34.6% had teaching experience exceeding 20 years, whereas 20.6% had less than five years of teaching experience. Regarding general knowledge of the teachers, (5.4%) of the teachers had a good level of knowledge. Only 63.6% of teachers were aware that ADHD students frequently struggled with task and activity organization, and only 7.5% of teachers had good knowledge of ADHD treatment, compared to 40.9% who had a good awareness of symptoms and diagnosis. Only the teachers' education level was significantly associated with their knowledge level of ADHD: 25% of teachers with a postgraduate degree had an overall good level of knowledge versus 2.7% of those with a diploma (P = 0.006). Conclusion: The findings of this study lead to the conclusion that elementary school instructors have an inadequate understanding of ADHD. Some teachers misunderstand the signs and general facts associated with ADHD, thereby indicating the need for further training in this area.

Assessment of Knowledge and Attitudes Toward Palliative Care and End-of-Life Decision-Making in Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Palliative care in Saudi Arabia has witnessed significant recent progress through the establishment of the Saudi Society for Palliative Care and the National Palliative Care Program. The objective of this study was to assess knowledge and attitudes regarding palliative care and end-of-life decision-making in Saudi Arabia's Eastern and Central provinces among individuals residing in these regions. METHODS: Utilizing a cross-sectional survey-based research design, we assessed knowledge and attitudes regarding palliative care and end-of-life decision-making in Saudi Arabia's Eastern and Central provinces. Participants were recruited through purposive sampling via social media. Data collection included demographic information, palliative care knowledge, attitudes toward palliative care, and cultural influences on end-of-life decisions. RESULTS: A total of 710 participants completed the survey, resulting in a response rate of 85%, with a balanced gender distribution, predominantly aged 25-54. Over half were healthcare providers, many possessing more than 15 years of healthcare experience. A substantial proportion had received formal palliative care training and had personal involvement in end-of-life decisions. While most participants demonstrated a good understanding of palliative care, knowledge gaps, especially regarding its timing, persisted. Generally, participants felt at ease discussing end-of-life care and believed in palliative care's effectiveness. Cultural influences on end-of-life decisions were perceived both positively and negatively, with some facing cultural challenges in palliative care. CONCLUSIONS: This study underscores a promising understanding of palliative care in Saudi Arabia alongside persistent misconceptions. It highlights the necessity for targeted education to rectify misperceptions, particularly concerning the initiation timing of palliative care. Cultural factors strongly impact end-of-life decisions, emphasizing the need for culturally sensitive healthcare discussions and provider training.

Large Ovarian Cystadenoma in an Adolescent Girl: A Case Report.

Ovarian cystadenomas are rare neoplastic tumors arising from the ovarian surface epithelium. While commonly observed in adult women, their occurrence in adolescents is exceedingly uncommon. The management of large ovarian cystadenomas in this age group poses unique challenges due to acute presentations and potential complications. We present the case of a 16-year-old girl who presented with sudden, severe abdominal pain and distension. Imaging revealed a 15 cm complex cystic mass originating from the right ovary, consistent with a cystadenoma. Urgent surgical intervention led to the right salpingo-oophorectomy, confirming the benign nature of the tumor. This report highlights the importance of a comprehensive approach to diagnosing and managing rare ovarian neoplasms in adolescents. Timely recognition, appropriate imaging, histopathological evaluation, and surgical intervention are crucial for optimal outcomes and reducing potential complications.

Clinical presentation and angiographic findings of acute myocardial infarction in young adults in Jazan region.

BACKGROUND: There is a paucity of information about the clinical features and angiographic findings in young patients with acute myocardial infarction (MI), especially in the Arab Peninsula countries. OBJECTIVE: The aim of this study was to assess the proposed risk factors, clinical presentation, and angiographic findings of acute myocardial infarction in young adults. METHODS: This prospective study included young (range, 18 to 45 years) patients who presented with acute MI based on clinical evaluation, laboratory investigation, and electrocardiogram, and they underwent a coronary angiography procedure. KEY FINDINGS: Data of 109 patients with a diagnosis of acute MI were collected. Patients' mean age was 39.98 ± 7.52 years (range, 31 to 45 years), and 92.7% (101) were male. Smoking was the highest risk factor in 67% of patients, obesity and overweight in 66%, sedentary lifestyle in 64%, dyslipidaemia in 33%, and hypertension in 28%. Smoking was the most common risk factor for acute MI in males (p = 0.009), whereas sedentary lifestyle was the most common risk factor in females (p = 0.028). Chest pain typical of acute MI was the most common presenting symptom in 96% of patients (p < 0.001). On admission, 96% of patients were conscious, and 95% were oriented. On angiography, the left anterior descending artery (LAD) was affected in 57%, the right coronary artery (RCA) was affected in 42%, and the left circumflex artery (LCX) was affected in 32% of patients. The LAD was severely affected in 44%, the RCA was severely affected in 25.7%, and the LCX was severely affected in 19.26% of patients (p < 0.001). CONCLUSION: Smoking, obesity, sedentary lifestyle, dyslipidaemia, and hypertension were the most common risk factors for acute MI. Smoking was the most common risk factor in males and sedentary lifestyle in females. The LAD was the most commonly affected coronary artery, followed by the RCA and LCX arteries, with the same order for severity of stenosis.

Seasonal Influenza Vaccination Among Saudi Children: Parental Barriers and Willingness to Vaccinate Their Children in the Makkah Region.

INTRODUCTION: The influenza virus produces everything from seasonal epidemics to unexpected pandemics, making its prevention and management a worldwide public health challenge. The main method to prevent and control seasonal influenza is vaccination. Children responded quite successfully to influenza vaccinations, particularly live vaccines. Despite the strong recommendations and effectiveness of seasonal influenza vaccinations in children, some parents still hesitate and refuse to give their children the shot. OBJECTIVE: This study, given the importance of knowing the factors that contribute to parents' refusal of influenza vaccine, also aims to assess parental barriers and willingness to vaccinate their children in the Makkah region of Saudi Arabia. METHODOLOGY: This is a descriptive cross-sectional study conducted among Saudi parents in the Makkah region. For data collection, an online survey was conducted between December 1, 2022, and February 11, 2023. RESULTS: In total, 334 of the parents participated in our study. The result shows that there is a significant association between parents' gender and receiving the flu vaccine, with significantly more females (52.4%). Regarding the willingness to get the vaccine, the majority of the parents reported that they will get the vaccine and vaccinate their children, and the most common barrier that prevents parents from vaccinating their children is that they do not need it because they are healthy (21.48%). Furthermore, there is a strong relationship between educational level and knowledge about seasonal influenza vaccination; the majority of parents at each level of education have poor knowledge regarding influenza vaccines. In addition, nearly all of our participants (96.7%) believed the information provided by the Saudi Ministry of Health as well as the advice of their physicians. CONCLUSION: This study highlights the need to increase awareness, educate the parents in the Makkah region about the importance of the influenza vaccine, and encourage them to vaccinate their children.

A Cross-Sectional Study on Public Awareness About Child Sexual Abuse in Makkah, Saudi Arabia.

BACKGROUND: Child sexual abuse is a very serious and dangerous problem. It has long-term consequences and may impact children and follow them into adulthood. Without exception, regardless of their cultures and religious beliefs, all communities are vulnerable to child sexual abuse (CSA). OBJECTIVE: Our aim in this study is to assess the level of public (caregivers) awareness of CSA in Makkah and Jeddah, Saudi Arabia. METHODOLOGY: A cross-sectional study was conducted in Makkah and Jeddah. The target populations were Saudi parents, caregivers, and teachers who are in daily contact with children. The participants were selected randomly (n=417), and were requested to complete a questionnaire that was later analyzed using the IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. RESULTS: 369 from 417 responders were females (88.5%), while 48 were males (11.5%). About 90.2% of the responders acknowledged the existence of the child sexual abuse problem. About 95.7% of the caregivers were aware of physical, social, and psychological consequences of child sexual abuse. In contrast, only 33.8% of the responders were aware of existence of social agencies and organizations that provide supportive services to the victims of child sexual abuse. CONCLUSION: In conclusion, the study found a high rate of awareness in the caregivers who recognize the problem of child sexual abuse (CSA) and are aware of its magnitude and impact on children's well-being. However, these results demonstrate the need for more education of the public about the mandatory laws regarding child sexual abuse.

Management and clinical outcomes of patients with homozygous familial hypercholesteremia in Saudi Arabia.

We report the incidence, patient characteristic with clinical outcomes in patients with homozygous familial hypercholesterolemia (HoFH) in Saudi Arabia. This is a retrospective and prospective, single center study which included 37 patients 14 years and older enrolled and followed up between 2018-2021 for three years. 46% were females, 78% were offspring of consanguineous marriage. LDLR mutation was in 78% and LDL-C/LDLRAP in 3% of patients. Mean LDL-C at the first presentation was 14.2±3.7 mmol/L, average Dutch lipid score was 20.9±6.24. LDL apheresis was performed on 70% of patients. Most patients were on ezetimibe (92%), high-dose statins ( 84%) and  PCSK9 inhibitors (32%). 48.6% had aortic stenosis, out of which 30% had severe aortic stenosis. Ten underwent aortic valve surgery (5 mechanical valve, 3 Ross procedure, 1 aortic valve repair, 1 bioprosthetic valve) and one had transcatheter aortic valve implantation (TAVI). Coronary artery bypass surgery (CABG) was performed on 32% and percutaneous intervention (PCI) on 11% of patients. HoFH patients have complex diseases with high morbidity and mortality, and benefit from a highly specialized multidisciplinary clinic to address their clinical needs. Although there are several therapeutic agents on the horizon, early diagnosis, and treatment of HoFH remain critical to optimize patient outcomes.

Effects of COVID-19 on Pediatric Cancer Care: A Multicenter Study of 11 Middle Eastern Countries.

During the COVID-19 pandemic, major challenges are facing pediatric cancer centers regarding access to cancer centers, continuity of the anti-cancer therapy, hospital admission, and infection protection precautions. Pediatric oncologists actively treating children with cancer from 29 cancer centers at 11 countries were asked to answer a survey from May 2020 to August 2020 either directly or through the internet. COVID-19 pandemic affected the access to pediatric cancer care in the form of difficulty in reaching the center in 22 (75.9%) centers and affection of patients' flow in 21 (72.4%) centers. Health care professionals (HCP) were infected with COVID-19 in 20 (69%) surveyed centers. Eighteen centers (62%) modified the treatment guidelines. Care of follow-up patients was provided in-hospital in 8(27.6%) centers, through telemedicine in 10 (34.5%) centers, and just delayed in 11 (38%) centers. Pediatric oncologists had different expectations about the future effects of COVID-19 on pediatric cancer care. Seventy-six percent of pediatric oncologists think the COVID-19 pandemic will increase the use of telemedicine. Fifty-five percent of pediatric oncologists think if the COVID-19 pandemic persists, we will need to change chemotherapy protocols to less myelosuppressive ones. Collaborative studies are required to prioritize pediatric cancer management during COVID-19 era.

De Novo Mutation of the ADAMTS13 Gene with Mesenteric Ischemia in an Infant with Congenital Thrombotic Thrombocytopenic Purpura.

INTRODUCTION: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare autosomal recessive disease characterized by ADAMTS13 deficiency or a severe decrease in its activity that is caused by homozygous or combined heterozygous mutations in its encoding gene. Here, we describe a de novo genetic mutation of the ADAMTS13 gene and a rare complication of cTTP in a neonate. Case Presentation. A full-term baby boy developed tachypnea, bradycardia, and oxygen desaturation at 2 h of life and was shifted to the newborn intensive care unit. He was oliguric in the first 24 h of life and had one episode of epistaxis. Blood-stained urine was observed in the urine catheter, and a coffee-ground-colored fluid was drained from the orogastric tube. Histopathological analysis revealed gastric perforation with features of ischemic insult. On day 8, genetic analysis confirmed the diagnosis of autosomal recessive familial thrombotic thrombocytopenic purpura and revealed a unique homozygous deletion mutation on exon 23 of ADAMTS13: c.2883del p.(Cys962Alafs ∗ 3). CONCLUSION: cTTP is a rare life-threatening autosomal recessive disease with a high mortality rate. Early detection and initiation of aggressive treatment with plasma infusion could be a life-saving strategy in such cases.

Hereditary Hemochromatosis Associated With Idiopathic Refractory Aplastic Anemia in a Five-Year-Old Boy: A Case Report.

Hereditary hemochromatosis (HH) is a multisystem disease characterized by iron overload and various clinical presentations, including cirrhosis, diabetes mellitus, and heart failure. HH can be caused by the human homeostatic iron regulator (HFE) and non-HFE gene mutations. Aplastic anemia is a rare, life-threatening bone marrow failure in which fat replaces pluripotent stem cells, resulting in pancytopenia and hypoplasia of bone marrow. We present a case of a five-year-old-boy who initially presented with a large ecchymosis located at the right side of the chest and abdomen. These started suddenly after minor trauma. Later, he was diagnosed with idiopathic aplastic anemia and treated with immunosuppressive therapy (IST). As part of the workup for pancytopenia, we ordered whole exome sequencing (WES) and diagnosed the patient with autosomal recessive hereditary hemochromatosis (ARHH). The ARHH is caused by HFE pathogenic gene mutation variant (c.187C>G p homozygous genotype). After six months of IST, he still had persistent disease. Human leukocyte antigen (HLA) typing showed he has a sister who is a full match but also has ARHH. Because of this, a haploidentical hematopoietic stem cell transplantation (hHSCT) from the father was performed. The hHSCT had a successful outcome. We suggest that in children with idiopathic aplastic anemia, physicians should be aware of the possibility of co-existing hereditary hemochromatosis or secondary hemochromatosis. Serum ferritin and transferrin saturation should also be measured regularly in order to detect early hemochromatosis.

Circumcision in Hemophilia: A Multicenter Experience.

BACKGROUND: Hemophiliac patients and their families have social pressure to undergo circumcision, despite the potential complications. The objective of this study was to report our experience in the circumcision of hemophilia patients. MATERIALS AND METHODS: We included 35 patients with hemophilia who had circumcision in 3 centers from January 2010 to August 2019. Their age ranged between 0.3 months and 8 years. Hemophilia a was classified as mild (n=3), moderate (n=4), and severe (n=28). Patients received 2 doses of factor VIII concentrate 50µ/kg, 1 hour before the procedure and 12 hours after it. RESULTS: Four neonates were diagnosed with hemophilia after circumcision because of prolonged bleeding. Two patients with severe hemophilia A had bleeding after hospital discharge (6.5%). They received additional factor concentrate, and 1 patient had an extra stitch. Two patients had wound gaping (6.5%), and 1 patient had a wound infection (3.2%). CONCLUSION: Hemophilia is not an absolute contraindication for circumcision. Circumcision of hemophilic children should be performed under appropriate conditions in hemophilia centers. Bleeding is not frequent but could be serious.

Indolent keratitis due to fungus of Malbranchea species. A case report.

INTRODUCTION: Keratitis caused by saprophytic fungi is on the rise in rural areas, often caused by ocular trauma with wooden objects. Early detection of causative organisms and sustained, supervised management can prevent visual disabilities. CASE PRESENTATION: A middle-aged patient from a rural, semi-arid region who presented with pain, redness, and a foreign-body sensation in his left eye resulting from a corneal ulcer induced by trauma from a wooden stick. Due to a history of uncontrolled diabetes and progression of his corneal lesions, he was admitted to our institution for treatment of infectious keratitis. Microbiological examination of corneal scrapings revealed thin, septate hyaline hyphae without conidia or conidiophores, and the patient was diagnosed with a fungal keratitis caused by a Malbranchea species. Though the patient initially responded to treatment with topical natamycin, his condition worsened. He was subsequently successfully treated with topical amphotericin B (1 mg/mL) twice hourly and systemic antifungals. Four months after discharge, the patient returned with symptom recurrence. CONCLUSION: We report the case of a patient with a Malbranchea species causing a rare and recurrent fungal keratitis with corneal infiltrates, subsequently cured by medical management with salvaging of his vision. In patients with a suspected fungal keratitis, early treatment is crucial and should be combined with tight glycemic control for as long as 6 months after presentation to avoid recurrence.

Correlation of TTG IgA Level with Small Intestinal Histopathological Changes for Celiac Disease among Adult Saudi Patients.

BACKGROUND AND OBJECTIVES: According to recent guidelines, a diagnosis of celiac disease (CD) can be made without a biopsy, especially in children. There are no enough studies despite high prevalence and differences in genetic, race, and cultures. Therefore, we examined the correlation between tissue transglutaminase (TTG) and duodenal biopsy changes in our region because we are identical and different from others in culture, environment, and habits, and the correlation is same as that in different regions. METHODS: A retrospective cohort study at the Ministry of National Guard Health Affaires (NGHA) health care facilities that are distributed throughout kingdom of Saudi Arabia from April 19, 2015, till March 29, 2018. This study used the BESTCARE system that includes data from all NGHA facilities; data from 513 patients with CD were collected. All patients diagnosed with celiac disease aged 15 years or more, confirmed by improvement on gluten-free diet (GFD), and were not on GFD before endoscopy or serology test or both of them were included in the study, and the TTG IgA level was measured at the same time or within 2-3 months of biopsy date. The exclusion criteria were negative duodenal biopsy, which is less than 2; patients with negative biopsy and negative serology; patients who were on GFD before testing, and any patients known to have immunity diseases or illness causing mucosal changes. The TTG IgA level was measured in IU/ mL and was labeled as negative (<20 IU/mL) and positive (≥ 20 IU/mL) based on the cutoff value. However, Intestinal biopsy findings were identified as Marsh classification groups. RESULTS: One hundred thirty-four patients who met the inclusion criteria were included in the study. Median age of our sample was 24 years (16-37 years). Among these, 99 (73.88%) were female patients, whereas male patients were only 35 (26.12%). Histopathologic investigation of intestinal biopsy were Marsh 0 group was 16 cases (11.9%), Marsh 1 group was 8 cases (6%), Marsh 2 group was 4 cases (3%), Marsh 3a group was 32 cases (23.9%), Marsh 3b group was 64 cases (47.8%), and Marsh 3c group was 10 cases (7.5%). The TTG IgA antibody serology groups were <20 IU/mL in 13 cases (9.7%) and ≥20 IU/mL in 121 cases (90.3%). Among all patients with CD who had negative biopsy (Marsh 0 group), 16 (100%) of them had positive TTG IgA antibody. However, among patients with Marsh 1 group biopsy, 5 (62.5%) cases had negative TTG IgA antibody compared with 3 (37.5%) positive cases. Of the four cases (100%) with Marsh 2 group, all of them had positive TTG IgA antibody. However, in Marsh 3a group biopsy, 3 (9.4%) cases had negative TTG IgA antibody compared with 29 (90.6%) cases with positive TTG IgA antibody. Furthermore, among the patients with Marsh 3b group biopsy, 5 (7.8%) had negative antibody and 59 (92.2%) had positive serology. Of all biopsies of Marsh 3c group, 10 (100 %) had positive TTG IgA antibody. CONCLUSIONS: In perspective of high prevalence of CD in KSA, even more than western countries, we can pretend that positive TTG antibody tests can be applied for the diagnosis of CD without biopsy, particularly in symptomatic patients along with high titer, that is, 5-10 times the upper limit of normal (ULN). However, to validate it further, we need larger prospective studies in which duodenal biopsies should be taken according to recommended protocol and should be interpreted by experienced pathologist. Furthermore, biopsy is still needed in patients who do not show clinical improvement on a gluten-free diet and in cases with mildly or moderately elevated TTG IgA.

Effect of Metformin on Doxorubicin-Induced Memory Dysfunction.

Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.

Single-Incision Pediatric Endosurgery Cholecystectomy Performed by Residents in Children with Sickle Cell Disease.

Introduction: Few centers worldwide have advanced single-incision pediatric endosurgery (SIPES) for pediatric age group. Up to our knowledge this is the first study assessing the safety of SIPES cholecystectomy in children with sickle cell disease (SCD) done by surgical residents. Aims: To determine the feasibility, safety, and expediency of SIPES cholecystectomy in children with SCD performed by surgical residents. Materials and Methods: Retrospective study of all SIPES cholecystectomies performed in our unit from April 1, 2011 to March 31, 2018. We compared the outcome of SIPES cholecystectomy done by fellows and residents. SIPES Covidien 5-12 mm port was inserted through umbilicus. Long 50 cm laparoscope, straight regular instruments, and transabdominal gallbladder traction suture were used in all patients. The cystic duct and artery were identified and divided. The gallbladder is then dissected off the liver and extracted from the abdomen through the port. Results: Forty-three SCD patients underwent SIPES cholecystectomy for 7 years. Mean HbS was 37.56%. Mean age was 10 years. Twenty-four cases (56%) and 19 (44%) were performed by 8 fellows and 10 residents, respectively. Nine other procedures were done simultaneously with cholecystectomy and were excluded from the mean operative time (MOT). The MOT for all cases was 85 minutes, 78 minutes for fellows and 94 minutes for residents (P value is <.001). One extra port was inserted in 2 patients at the beginning of the series. Conclusion: SIPES cholecystectomy in children with SCD is safe and feasible if done by residents under supervision. Stepwise training is essential in this challenging surgery. Involving residents with other SIPES procedures and hands-on minimally invasive surgery single port workshops help them in improving their skills.

Is It Safe for Trainees to Perform Single-Incision Pediatric Endosurgery Splenectomy?

INTRODUCTION: Few centers worldwide have advanced single-incision pediatric endosurgery (SIPES) splenectomy. The safety and feasibility of SIPES performed by trainees were not assessed before. SIPES splenectomy is a demanding technique that needs high level of skills. This is the largest series of 39 SIPES splenectomies performed by 14 trainees in one single center. AIMS: To assess the safety, feasibility, and technical challenges of SIPES splenectomy performed by trainees and to compare it with other published series. MATERIALS AND METHODS: Retrospective study of all patients operated with SIPES splenectomy for 7 years. SIPES port was inserted through 1.5 cm umbilical incision. One type of port and straight regular instruments were used in all cases. RESULTS: Forty-nine patients underwent SIPES splenectomy. Eighty percent was done by our trainees. Six cholecystectomies were done simultaneously. Forty-five patients with sickle cell disease, two with thalassemia, one spherocytosis, and one Fanconi's anemia. Mean operative time (MOT) for splenectomy was 182 minutes (130-190) and 251 minutes for splenectomy with cholecystectomy (230-270) depending on severity of adhesions and size of the spleen; P value <.001. Two conversions have to be opened due to bleeding. There is neither wound infection nor incisional hernia up to date. CONCLUSION: SIPES splenectomy is safe and feasible when performed by surgical trainees without adding any morbidity to the patient. Learning curve can quickly improve with more exposure of trainee to different SIPES procedures and hands-on workshops. More than one procedure could be done at the same time. It has excellent cosmesis and almost invisible scar.

Mps1 Phosphorylates Its N-Terminal Extension to Relieve Autoinhibition and Activate the Spindle Assembly Checkpoint.

Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a "prone-to-autophosphorylate" Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells.