Bartter and Gitelman syndromes:Spectrum of clinical manifestations caused by different mutations

Bartter and Gitelman syndromes(BS and GS) are inherited disorders resulting in defects in renal tubularhandling of sodium,potassium and chloride.Previously considered as genotypic and phenotypic heterogeneous diseases,recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition.Although they share some characteristic metabolic abnormalities such as hypokalemia,metabolic alkalosis,hyperplasia of the juxtaglomerular apparatus with hyperreninemia,hyperaldosteronism,the clinical and laboratory manifestations may not always allow distinction between them.Diuretics tests,measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change(< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS,except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists.The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children.Clinical symptoms and biochemical markers of GS and classic form of BS(type III) may overlap and thus genetic analysis may specify the real cause of symptoms.However,although genetic analysis is available,its use remains limited because of limited availability,large gene dimensions,lack of hot-spot mutations,heavy workup time and costs involved.Furthermore,considerable overlap exists between the different genotypes and phenotypes.Although BS and GS usually have distinct presentations and are associated with specific gene mutations,there remains considerable overlap between their phenotypes and genotypes.Thus,they are better described as a spectrum of clinical manifestations caused by different gene mutations.

Metabolic bone disease in the preterm infant: Current state and future directions

Neonatal osteopenia is an important area of interest for neonatologists due to continuing increased survival of preterm infants. It can occur in high-risk infants such as preterm infants, infants on long-term diuretics or corticosteroids, and those with neuromuscular disorders. Complications such as rickets, pathological fractures, impaired respiratory function and poor growth in childhood can develop and may be the first clinical evidence of the condition. It is important for neonatologists managing such high-risk patients to regularly monitor biochemical markers for evidence of abnormal bone turnover and inadequate mineral intake in order to detect the early phases of impaired bone mineralization. Dual-energy X-ray absorptiometry has become an increasingly used research tool for assessing bone mineral density in children and neonates, but more studies are still needed before it can be used as a useful clinical tool. Prevention and early detection of osteopenia are key to the successful management of this condition and oral phosphate supplements should be started as soon as is feasible.

Significance of platelet count in children admitted with bronchiolitis

AIM To determine the true prevalence of thrombocytosis in children less than 2 years of age with bronchiolitis,its association with risk factors,disease severity and thromboembolic complications.METHODS A retrospective observational medical chart review of 305 infants aged two years or less hospitalized for bronchiolitis.Clinical outcomes included disease severity,duration of hospital stay,admission to pediatric intensive care unit,or death.They also included complications of thrombocytosis,including thromboembolic complications such as cerebrovascular accident,acute coronary syndrome,deep venous thrombosis,pulmonary embolus,mesenteric thrombosis and arterial thrombosis and also hemorrhagic complications such as bleeding(spontaneous hemorrhage in the skin,mucous membranes,gastrointestinal,respiratory,or genitourinary tracts).RESULTS The median age was 4.7 mo and 179 were males(59%).Respiratory syncytial virus was isolated in 268(84%),adenovirus in 23(7%) and influenza virus A or B in 13(4%).Thrombocytosis(platelet count > 500 × 109/L) occurred in 88(29%;95%CI:24%-34%),more commonly in younger infants with the platelet count declining with age.There was no significant association with the duration of illness,temperature on admission,white blood cell count,serum C-reactive protein concentration,length of hospital stay or admission to the intensive care unit.No death,thrombotic or hemorrhagic events occurred.CONCLUSION Thrombocytosis is common in children under two years of age admitted with bronchiolitis.It is not associated with disease severity or thromboembolic complications.

Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

BACKGROUND The coronavirus disease 2019(COVID-19),a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide,was described to be frequently accompanied by extrapulmonary manifestations,including liver dysfunction.Liver dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 patients.AIM To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.METHODS The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed.Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways.The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis,fibrosis,non-alcoholic fatty liver disease(NAFLD),and hepatitis A/B/C.Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.RESULTS Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,DNAJB1,IGF2,EGFR,and HDGF.Concordantly,the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling(liver cirrhosis,Fibrosis,NAFLD,and hepatitis A/B/C).Moreover,we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function,including cytochrome P450 family members,ACAD11,CIDEB,GNMT,and GPAM.Consequently,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity.In correspondence with the RNA-seq data analysis,we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction.CONCLUSION Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling,mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.

Profiling cellular bioenergetics, glutathione levels, and caspase activities in stomach biopsies of patients with upper gastrointestinal symptoms

AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions.METHODS: Biopsies were obtained from the stomachs of two groups of patients(n = 40) undergoing fiberoptic endoscopy due to upper gastrointestinal symptoms. In the first group(n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption(cellular respiration), cellular adenosine triphosphate(ATP), glutathione(GSH), and caspase activity. In the second group of patients(n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level.RESULTS: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate(mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min-1 mg-1, ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high andATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration(O2. μmol/L min-1 mg-1) was slightly higher in the corpus than the antrum(0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues(310 ± 135 vs 322 ± 155, P = 0.692).CONCLUSION: The corpus mucosa was metabolically more active than the antrum tissue. The data in this study will help in understanding the pathophysiology of gastric mucosa.

Strongyloides hyper-infection causing life-threatening gastrointestinal bleeding

A 55-year old male patient was diagnosed with strongy- loides hyper-infection with stool analysis and intestinal biopsy shortly after his chemotherapy for myeloma. He was commenced on albendazole anthelmintic therapy. After initiation of the treatment he suffered life- threatening gastrointestinal (GI) bleeding. Repeated endoscopies showed diffuse multi-focal intestinal bleeding. The patient required huge amounts of red blood cells and plasma transfusions and correction of haemostasis with recombinant activated factor Ⅶ. Abdominal aorto-angiography showed numerous micro- aneurysms (‘berry aneurysms’) in the superior and inferior mesenteric arteries’ territories. While the biopsy taken prior to the treatment with albendazole did not show evidence of vasculitis, the biopsy taken after initiation of therapy revealed leukoclastic aggregations around the vessels. These findings suggest that, in addition to direct destruction of the mucosa, vasculitis could be an important additive factor causing the massive GI bleeding during the anthelmintic treatment. This might result from substances released by the worms that have been killed with anthelmintic therapy. Current guidelines advise steroids to be tapered and stopped in case of systematic parasitic infections as they might reduce immunity and precipitate parasitic hyper-infection. In our opinion, steroid therapy might be of value in the management of strongyloides hyper- infection related vasculitis, in addition to the anthelmintic treatment. Indeed, steroid therapy of vasculitis with other means of supportive care resulted in cessation of the bleeding and recovery of the patient.

The Use of Low Molecular Weight Heparin for Venous Thromboembolism Prophylaxis in Medical Patients: How Much Are We Adherent to the Guidelines?

Background: Venous thromboembolism (VTE) is a common complication seen during or after hospitalization that manifests as deep venous thrombosis (DVT) and/or pulmonary embolism (PE). PE is considered the commonest preventable cause of death during and/or after hospitalization. Thus, pharmacological and mechanical methods are used to prevent VTE in hospitalized patients. Despite the availability of guidelines for VTE prophylaxis, it is crucial to assess the adherence and adaptation of the institution to these guidelines. Purpose: This study aimed to investigate adherence to the American College of Chest Physicians (ACCP) 2012 VTE prophylaxis guidelines in hospitalized medical patients in a tertiary care hospital in the United Arab Emirates. Methods: An observational prospective design was utilized in this study. To achieve the purpose, primary and secondary end points were identified to be the core of the investigation. The primary end points were: the incidence of bleeding, VTE, and cardiovascular events. While the secondary end points were: dose and indication validity for prophylaxis, VTE and bleeding risk assessments, adverse drug events (ADE) other than bleeding, appropriate monitoring when on low molecular weight heparin (LMWH) and the presence of contraindication at the time of prescribing LMWH. Results: 16 patients (20%) out of the total 80 met one or more of the primary end points. The vast majority of patients (81.25%) developed bleeding, while VTE was seen in one case only during hospitalization. 11 patients (13.75%) received LMWH while a contraindication was present. 15 patients (18.75%) who were prescribed LMWH had an International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding risk score of ≥7. However, 5 out of 13 patients (38.46%) who developed bleeding had a bleeding score of ≥7, and the relationship between bleeding score of ≥7 and the development of bleeding was statistically significant (p = 0.047). When investigating the doses that were utilized, 40% were prescribed an inappropriate dose. Conclusion: Various factors played a role in the inappropriateness of VTE prophylaxis such as;poor adherence to VTE guidelines, inappropriate dosing and monitoring, and not evaluating the bleeding risk. Hence, to be able to achieve effective VTE prophylaxis, these factors need to be addressed through adherence to and adaptation of the ACCP 2012 VTE prophylaxis guidelines.

Is forced oscillation technique the next respiratory function test of choice in childhood asthma

Respiratory diseases, especially asthma, are common in children. While spirometry contributes to asthma diagnosis and management in older children, it has a limited role in younger children whom are often unable to perform forced expiratory manoeuvre. The development of novel diagnostic methods which require minimal effort, such as forced oscillation technique(FOT) is, therefore, a welcome and promising addition. FOT involves applying external, small amplitude oscillations to the respiratory system during tidal breathing. Therefore, it requires minimal effort and cooperation. The FOT has the potential to facilitate asthma diagnosis and management in preschool children by faciliting the objective measurement of baseline lung function and airway reactivity in children unable to successfully perform spirometry. Traditionally the use of FOT was limited to specialised centres. However, the availability of commercial equipment resulted in its use both in research and in clinical practice. In this article, we review the available literature on the use of FOT in childhood asthma. The technical aspects of FOT are described followed by a discussion of its practical aspects in the clinical field including the measurement of baseline lung function and associated reference ranges, bronchodilator responsiveness and bronchial hyperresponsiveness. We also highlight the difficulties and limitations that might be encountered and future research directions.

First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases:A 2020 Delphi consensus

Ulcerative colitis and Crohn’s disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract.The incidence and prevalence are on the rise worldwide,and the heterogeneity between patients and within individuals over time is striking.The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients.This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence-and expert opinion-based recommendations.Comprehensive up-to-date guidance is provided regarding diagnosis,evaluation of disease severity,appropriate and timely use of different investigations,choice of appropriate therapy for induction and remission phase according to disease severity,and management of main complications.

Prevalence and outcome of acute kidney injury,as defined by the new Kidney Disease Improving Global Outcomes guideline,in very low birth weight infants

AIM To evaluate the prevalence, risk factors and outcome of acute kidney injury(AKI) in very low birth weight(VLBW) infants. METHODS In this retrospective study of VLBW infants, we analyzed the prevalence of AKI, as defined by changes in serum creatinine and urine output, associated risk factors and outcomes.RESULTS A total of 293 VLBW infants(mean gestational age 28.7 wk) were included, of whom 109 weighed less than 1000 g at birth. The overall prevalence of AKI was 11.6%(22% in infants with a birth weight under 1000 g and 5.4% those heavier). A total of 19(55%) affected infants died, with a mortality rate of 58% in infant less than 1000 g and 50% in those heavier. After adjusting for confounding variables, only necrotizing enterocolitis(NEC) remained associated with AKI, with odds ratio of 4.9(95%CI: 1.9-18.6). Blood pressure and glomerular filtration rate(GFR) were not different between affected infants and the others upon discharge from hospital. A normal GFR was documented in all affected infants at one year of age.CONCLUSION Using Kidney Disease Improving Global Outcomes definition of AKI, it occurred in over 10% of VLBW infants,more commonly in infants with lower birth weight. NEC was an independent associated risk factor. Renal function, as defined by GFR, was normal in all surviving affected infants 10 to 12 mo later.

Blunt traumatic tension chylothorax:Case report and minireview of the literature

Tension chylothorax following blunt thoracic trauma is an extremely rare condition.Here we report such a case and review its management.A 31-year-old man was involved in a road traffic collision.The car rolled over and the patient was ejected from the vehicle.On arrival at the Emergency Department the patient was conscious and haemodynamically stable.Clinical examination of the chest and abdomen was normal.The patient had sustained fractures of the sixth cervical vertebra and the tenth thoracic vertebra,left pleural effusion,haematoma around the descending aorta and fracture of the right clavicle.The left pleural effusion continued to increase in size and caused displacement of the trachea and mediastinum to the opposite side.An intercostal chest tube was inserted on the left side on the second day.It drained 1500 mL of milky,bloodstained fluid.We confirmed the diagnosis of chylothorax by a histopathological examination of a cell block prepared from the left pleural effusion using Oil red O stain.The patient was managed conservatively with chest tube drainage and fat free diet.The chylothorax completely resolved on the eighth day after the injury.The patient was discharged home on day 16.

Before the Jury Is out on Cinacalcet’s Cardiovascular Effects in Hemodialysis Patients: Is Troponin a Missing Link?

Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondary hyperparathyroidism may reduce cardiac endpoints, the effect of the calcimimetic agent, cinacalcet, remains controversial. This retrospective study aimed at evaluating troponin levels in hemodialysis patients with severe secondary hyper parathyroidism (SHPT) who are on cinacalcet vs controls on conventional treatment. In addition, clinical outcomes including all-cause, cardiovascular morbidity and mortality were compared among both groups. A decline in Troponin I levels was observed in the cinacalcet group, this however was not translated clinically into improved survival. In fact, all-cause and cardiac mortality was similar in the two groups. Conversely, comparison of the incidence of cardiovascular events revealed lower rates in the cinacalcet group including cardiac, cerebral and peripheral vascular complications. Given some of our study limitations, further long-term, placebo-controlled trials are necessary to definitively establish the effect of cinacalet on cardiac biomarkers and ultimately its impact on clinical outcomes.

Psychiatric Complications of Obesity and Its Treatment: A Brief Review

Obesity—defined as a body mass index (BMI) of 30 kg/m2 or more—is associated with a wide range of medical and psychiatric complications. Physical co-morbidities include: insulin resistance, type 2 diabetes mellitus, dyslipidemia, asthma, hypertension, coronary heart disease, osteoarthritis of the knee and polycystic ovary syndrome. Mental health problems are particularly more common among individuals presenting for treatment of obesity than those in the community. They have higher rates of depression, anxiety, increased substance abuse and an increased prevalence in eating disorders. It has been estimated that up to 60% of extremely obese individuals have been suffering from an Axis I psychiatric disorder;most commonly mood and anxiety disorders. Obstructive sleep apnea (OSA) can occur with obesity and can also lead to sleep disorders and psychiatric complications. Up to 40% of patients with sleep apnea were found to have affective disorder or alcohol abuse. Weight loss medications and surgery may add to the problem of psychological complications of obesity. For example, in 2008, rimonabant development was discontinued by manufacturer as it has been associated with an increased risk of adverse psychiatric events including suicidal ideation and suicidal behavior. On the other hand, the prevalence of obesity is also high among patents with psychiatric illness, which can be caused by the effects of psychotropic medications which can lead to increased appetite, weight gain, sedation and psychomotor retardation. Obesity is reported in more than 60% of patients with schizophrenia and bipolar disorder. Food intake is regulated by several neurotransmitters, peptides and amino acids. Antipsychotics which block dopamine D2 receptors increase appetite and result in significant weight gain, while drugs that increase brain dopamine concentration are anorexigenic.

Alarming Presentation of a Seemingly Common Condition in a Patient with Renal Impairment

We received a 23-year-old male, working in the Army for 18 months, with advanced renal impairment, haemoptysis and hyperkalemia. An impression of the pulmonary renal syndrome was made and he was managed aggressively with haemodialysis, plasma exchange and pulsing with methyl prednisolone. His condition improved, but the renal functions did not. The vasculitic workup including Extractable Nuclear Antigen (ENA) and Anti-Neutrophil Cytoplasmic Antibody (ANCA) which were sent on admission came out to be negative. As he apparently responded to the initial management protocol, he was subjected to renal biopsy which did not reveal any vasculitis but was consistent for end-stage renal disease. Subsequently he was subjected to lung biopsy which also was not supportive for vasculitis. However, we concluded that the initial pointers for Wegener’s granulomatosis were misleading. The haemoptysis entirely subsided as the congestion improved. He was maintained on Haemodialysis three times per week schedule and discharged to the peripheral health care facility.

Renal Allograft Thrombosis in the Early Post Transplant Period

Renal allograft thrombosis involving either the renal artery or the veins is a well known entity in clinical practice. This complication of the renal transplant surgery is more common in the early part of the post transplant period and it is usually associated with acute antibody mediated rejection. This more commonly occurs in the paediatric renal transplant and also seems to have some relation to the duration of peritoneal dialysis pretransplant. However, the occurrence of graft thrombosis in isolation without clinical or histological graft rejection is not rare. We encountered a patient in whom the renal allograft thrombosis occurred after 6 weeks of commercial renal transplantation without any histological evidence of rejection.

Hussein Hassan Okasha,Mahmoud Wahba,Eva Fontagnier,Abeer Abdellatef,Hani Haggag,Sameh

BACKGROUND Almost half of the patients with colorectal cancer(CRC)will experience localregional recurrence after standard surgical excision.Many local recurrences of colorectal cancer(LRCC)do not grow intraluminally,and some may be covered by a normal mucosa so that they could be missed by colonoscopy.Early detection is crucial as it offers a chance to achieve curative reoperation.Endoscopic ultrasound(EUS)is mainly used in CRC staging combined with cross-section imaging study.EUS can provide an accurate assessment of sub-mucosal lesions by demarcating the originating wall layer and evaluating its echostructure.EUS fineneedle aspiration(FNA)provides the required tissue examination and confirms the diagnosis.CASE SUMMARY We report a series of five cases referred to surveillance for LRCC with negative colonoscopy and/or negative endoscopic biopsies.EUS-FNA confirmed LRCC implanted deep into the third and fourth wall layer with normal first and second layer.CONCLUSION Assessment for LCRR is still problematic and may be very tricky.EUS and EUSFNA may be useful tools to exclude local recurrence.

Experience with Post Transplant Parathyroidectomy in Gulf Region and Literature Review

Sustained elevation of parathyroid hormone (PTH) levels is not uncommon post renal transplantation. Though in the majority of patients, it gradually normalizes, on average 5% of transplanted patients require parathyroidectomy (PTX). However, PTX itself has been associated with deterioration in allograft function and even completes graft loss seen with both total and subtotal PTX as well as an increased rate of acute rejection. The aim of this study was to determine the effect of post transplant partial PTX on allograft function in our patients as well as the incidence of acute rejection. Our results show that post transplantation, subtotal PTX, was successful in achieving metabolic control while preserving graft function without an increased incidence of acute rejection. Retention of sufficient residual parathyroid tissue with partial PTX might account for favorable outcome in our study. Despite this, surgery for advanced hyperparathyroidism should optimally take place in the pre-transplant period.

Patients Returning to Dialysis after Failed Kidney Transplant: How Do They Fare? A Gulf Perspective

An increasing number of failed transplant patients returning to dialysis (FTRD) have been observed with reported worse survival compared to transplant-naive dialysis (TxN) patients. This study aimed to assess outcomes of FTRD vs. matched TxN controls in a Gulf region multi-center trial of 800 HD patients. Similar mortality was seen, likely due to earlier start and better HD adequacy in FTRD. Younger age, less diabetes and living donor transplantation in majority with 27% graft nephrectomy (Nx) might also confer benefits. Subgroup analysis of Nx patients showed more hospitalizations and prior rejection episodes with lower graft survival. The deaths, however, oc-curred only in nonNx group and are likely explained by older age, longer duration on HD, more prevalence of diabetes and CAD. FTRD showed similar survival to TxN. Early intensive HD might account for the benefit. Whether Nx confers advantage is unclear because of the small sample size.

The Effect of Balanced Hypocaloric Diet on the Anthropometric and Basic Metabolic Indicators in Infertile Women with Gluteofemoral Obesity

Purpose: To evaluate the effect of balanced hypocaloric diet therapy on the anthropometric and basic metabolic indicators in obese women with infertility. Methods: The follow up interventional clinical study included 23 infertile women in reproductive age with grade I gluteofemoral obesity. All patients have prescribed a balanced hypocaloric diet (1200 kcal/day), underwent exercise and behavioral therapy. Before and after 12-month treatment, an anthropometric study was conducted, determining the level of metabolic and hormonal indicators. Results: The total final number of study participants was 20 patients. A decrease in body weight was achieved in 87% of patients from 4 to 24 kg, on the average, by 10.58 ± 5.70 kg, there was also a decrease in BMI from 32.53 ± 1.40 to 28.55 ± 2.50 kg/m2 (p 0.001). The decrease in body weight was accompanied by a statistically significant decrease in leptin levels (p 0.001), E1 (p = 0.049), E2 (p = 0.032), fasting glucose (p 0.001), HOMA-IR (p = 0.002), cholesterol (p < 0.001), TG (p = 0.004), LDL-C (p = 0.001), atherogenic index of plasma (p <0.001) and an increase in progesterone levels (p = 0.030). Ovulatory menstrual cycles were resumed in all women (p = 0.007) and pregnancy occurred within a year in 1 patient. Conclusion: The implementation of a hypocaloric diet for 12 months in infertile women with first-degree obesity helps to normalize metabolic and hormonal indicators, reduces body weight and restores ovulatory menstrual cycle in all patients.

Comprehensive review into the challenges of gastrointestinal tumors in the Gulf and Levant countries

Although gastrointestinal stromal tumors(GISTs)are rare,with an incidence of 1/100000 per year,they are the most common sarcomas in the peritoneal cavity.Despite considerable progress in the diagnosis and treatment of GIST,about half of all patients are estimated to experience recurrence.With only two drugs,sunitinib and regorafenib,approved by the Food and Drug Administration,selecting treatment options after imatinib failure and coordinating multidisciplinary care remain challenging.In addition,physicians across the Middle East face some additional and unique challenges such as lack of published local data from clinical trials,national disease registries and regional scientific research,limited access to treatment,lack of standardization of care,and limited access to mutational analysis.Although global guidelines set a framework for the management of GIST,there are no standard local guidelines to guide clinical practice in a resource-limited environment.Therefore,a group of 11 experienced medical oncologists from across the Gulf and Levant region,part of the Rare Tumors Gastrointestinal Group,met over a period of one year to conduct a narrative review of the management of GIST and to describe regional challenges and gaps in patient management as an essential step to proposing local clinical practice recommendations.