Scalpel and strife: Assessing the impact of Sudan's ongoing civil war on surgical practice and healthcare delivery.

BACKGROUND: This study aims to shed light on the profound ramifications of the military conflict that started in April 2023 on surgical practice in Sudan. METHODS: This is a survey-based study. The survey link was disseminated to Sudanese medical practitioners via various social media (WhatsApp, Telegram, X (previously twitter) and Facebook) channels. We included only responses from medical practitioners working in the surgical specialities. RESULTS: A total of 90 responses have been collected. All participants were working in surgical service provision institutes. Sixty per cent of the responses were from the age group 25-35 years old, and two-thirds of the total cohort either left Sudan or was internally displaced because of the conflict. Moreover, 51% are no longer practising because they had to flee the conflict area (75%) or because the hospital is out of service (20%). There was a significant drop in the average number of emergency and elective lists. CONCLUSION: The military conflict affected Sudan's already strained health system. There was a significant drop in the average number of emergency and elective lists with surgeons out of practice because they had to flee the conflict area and hospitals were out of service.

Hypercalcemia as a rare presentation of hyaline fibromatosis syndrome from different Sudanese families: two case reports.

BACKGROUND: Hyaline fibromatosis syndrome is a rare progressive autosomal recessive connective tissue disorder caused by a mutation in the ANTXR2/CMG2 gene. According to its severity, patients may present with skin nodules or visceral infiltration, which carries a poor prognosis. Hypercalcemia has not been reported as a presenting feature of this syndrome. Stimulation of osteoclasts by inflammatory factors and immobilization--induced hypercalcemia have played role in the pathophysiology. To our knowledge, this is the first report of hypercalcemia-associated hyaline fibromatosis syndrome. CASE PRESENTATION: Here, we describe cases of two Sudanese patients, a boy aged 9 months and a girl aged 3.5 years with hypercalcemia as an associated presenting feature of hyaline fibromatosis syndrome. Other features include gingival hypertrophy, painful joint swellings, and restriction of movement, which was misdiagnosed as juvenile rheumatoid arthritis. Workup showed normal phosphate, normal to mildly elevated parathyroid hormone, low vitamin D 25. Genetic testing confirmed the mutation of the ANTXR2/CMG2 gene. Both patients responded well to medical therapy for hypercalcemia, but one of them with the severe form of juvenile hyaline fibromatosis died due to sepsis, while the other one has maintained normocalcemic status. CONCLUSIONS: These cases highlight the rare presentation of this syndrome and reflect the importance of biopsy and genetic testing in reaching the diagnosis, especially when the clinical presentation can mimic other inflammatory bone disorders. Calcium levels should be checked in such cases.

A Novel Splice-Site Deletion in the POU1F1 Gene Causes Combined Pituitary Hormone Deficiency in Multiple Sudanese Pedigrees.

Pathogenic variants within the gene encoding the pituitary-specific transcription factor, POU class 1 homeobox 1 (POU1F1), are associated with combined pituitary hormone deficiency (CPHD), including growth hormone, prolactin, and thyrotropin stimulating hormone deficiencies. The aim of the study was to identify genetic aetiology in 10 subjects with CPHD from four consanguineous Sudanese families. Medical history, as well as hormonal and radiological information, was obtained from participants' medical records. Targeted genetic analysis of the POU1F1 gene was performed in two pedigrees with a typical combination of pituitary deficiencies, using Sanger sequencing, and whole-exome sequencing was performed in the other two pedigrees, where hypocortisolism and additional neurologic phenotypes were also initially diagnosed. In POU1F1 gene (NM_001122757.2) a novel homozygous splice-site deletion-namely, c.744-5_749del-was identified in all 10 tested affected family members as a cause of CPHD. Apart from typical pituitary hormonal deficiencies, most patients had delayed but spontaneous puberty; however, one female had precocious puberty. Severe post-meningitis neurologic impairment was observed in three patients, of whom two siblings had Dyke-Davidoff-Masson syndrome, and an additional distantly related patient suffered from cerebral infarction. Our report adds to the previously reported POU1F1 gene variants causing CPHD and emphasises the importance of genetic testing in countries with high rates of consanguineous marriage such as Sudan. Genetic diagnostics elucidated that the aetiologies of hypopituitarism and brain abnormalities, identified in a subset of affected members, were separate. Additionally, as central hypocortisolism is not characteristic of POU1F1 deficiency, hydrocortisone replacement therapy could be discontinued. Elucidation of a genetic cause, therefore, contributed to the more rational clinical management of hypopituitarism in affected family members.

Ameliorate impacts of scopoletin against vancomycin-induced intoxication in rat model through modulation of Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK signaling pathways: Molecular study, molecular docking evidence and network pharmacology analysis.

Nephrotoxicity is an indication for the damage of kidney-specific detoxification and excretion mechanisms by exogenous or endogenous toxicants. Exposure to vancomycin predominantly results in renal damage and losing the control of body homeostasis. Vancomycin-treated rats (200 mg/kg/once daily, for seven consecutive days, i.p.) revealed significant increase in serum pivotal kidney function, oxidative stress, and inflammatory biomarkers. Histologically, vancomycin showed diffuse acute tubular necrosis, denudation of epithelium and infiltration of inflammatory cells in the lining tubular epithelium in cortical portion. In the existing study, the conservative consequences of scopoletin against vancomycin nephrotoxicity was investigated centering on its capacity to alleviate oxidative strain and inflammation through streamlining nuclear factor (erythroid-derived-2) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and prohibiting the nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (p38 MAPK) pathway. With respect to vancomycin group, scopoletin pretreatment (50 mg/kg/once daily, i.p.) efficiently reduced kidney function, oxidative stress biomarkers and inflammatory mediators. Moreover, histological and immunohistochemical examination of scopoletin-treated group showed remarkable improvement in histological structure and reduced vancomycin-induced renal expression of iNOS, NF-κB and p38 MAPK. In addition, scopoletin downregulated (Kelch Like ECH Associated Protein1) Keap1, P38MAPK and NF-κB expression levels while upregulated renal expression levels of regulatory protein (IκBα), Nrf2 and HO-1. Furthermore, molecular docking and network approach were constructed to study the prospect interaction between scopoletin and the targeted proteins that streamline oxidative stress and inflammatory pathways. The present investigations elucidated that scopoletin co-treatment with vancomycin may be a rational curative protocol for mitigation of vancomycin-induced renal intoxication.

Challenges in diagnosis and management of neonatal hyperparathyroidism in a resource-limited country: a case series from a Sudanese family.

Neonatal hyperparathyroidism is a rare disease caused by a homozygous inactivating mutation in the calcium sensing receptor gene. It presents early in life with life threatening manifestations of hypercalcemia, if left untreated the condition may be lethal. This is the first case series reported from Sudan. Three Sudanese siblings presented with severe symptoms of hypercalcemia in the form of polyuria, failure to thrive and multiple bone fractures. Serum calcium and parathyroid hormone levels were very high with low phosphate and normal alkaline phosphatase levels. Ultrasonography and sestamibi scan were normal and did not assist in diagnosing their condition. Medical management was a great challenge due to unavailability of medications such as parentral bisphosphonates and calcimimetics. Parathyroidectomy was inevitable. Tissue biopsies revealed parathyroid hyperplasia and no adenoma. Gene sequencing revealed a homozygous missense mutation: c 2038 C T p (Arg680Cys) in two siblings, both parents were heterozygous for the same missense mutation. Our report reflects the challenges in diagnosis and management of neonatal hyperparathyroidism in resource limited countries. We also highlight the importance of genetic testing in the diagnosis and management of such cases in countries with high rates of consanguineous marriage.

Aetiologies and clinical patterns of hypopituitarism in Sudanese children.

There is paucity of reported information regarding aetiology and clinical profile of hypopituitarism from resource-limited countries particularly in populations with high rates of consanguineous marriages. Here, we are reporting the first data on this aspect from Sudan. This is a descriptive, retrospective, hospital-based study, carried out in the two main paediatric endocrinology centres in Sudan (Gafaar Ibn Auf Paediatric Tertiary Hospital and Soba University Hospital, Khartoum) from January 2006 up to December 2014. Patients' records were reviewed for relevant demographical, clinical, hormonal and radiological data using pretested study forms. The study included 156 patients. One hundred and one patients were males (M: F = 1.8:1). The commonest age groups were adolescents (57.7%). Consanguinity was found in 77.8% of patients overall and 91% of patients with congenital aetiologies. The commonest clinical presentation was short stature (93.5%). Congenital causes (86.5%) were more prevalent than acquired causes (13.5%). There were six family clusters with multiple pituitary hormone deficiencies (MPHD) and three families with isolated growth hormone (GH) deficiency (IGHD). Most of the congenital cases with MPHD were phenotypic for PROP1 gene mutation (77.5% of sporadic cases and 50% of familial cases). Craniopharyngioma was the commonest of the acquired causes (10.2%). GH was the most frequent hormone deficient (89.7%). Abnormal Magnetic resonance imaging brain findings were significantly seen more in MPHD in comparison to IGHD. The genetic forms of hypopituitarism in populations with high rates of consanguineous marriage like Sudan may be higher than those reported internationally. Molecular genetic studies are, therefore, highly recommended.

Fanconi Bickel syndrome: clinical phenotypes and genetics in a cohort of Sudanese children.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare condition of carbohydrate metabolism, caused by a recessive defect in the facilitative glucose transporter GLUT2 encoded by the SLC2A2 gene and characterized by a wide spectrum of phenotypical features. There is a paucity of reported data on FBS from Sub-Saharan Africa. Here, we describe the clinical, biochemical and genetic characteristics of our patients with FBS from Sudan, a country with a high consanguinity rate. PATIENTS & METHODS: Eleven patients from ten unrelated Sudanese families were included. Clinical & biochemical data were documented and imaging studies done including bone survey and abdominal ultrasound. Liver biopsy was done to confirm the pathological diagnosis in 45% of cases and molecular genetics was performed through contribution with the Exeter genomics laboratory for ten patients. RESULTS: Reported consanguinity was 70% among our patients. Growth was significantly impaired at presentation with mean weights of (-5.3 ± 1.8) SD and heights (-5.4 ± 2.5) SD. Severe chest deformity was present in (27%) and all patients showed features of rickets at presentation. Three patients had neonatal diabetes requiring insulin therapy of which one has been reported before. Six families lost undiagnosed siblings with similar clinical presentations. We identified a total of four homozygous pathogenic SLC2A2 variants in our patients, one of whom had a novel mutation. CONCLUSIONS: FBS is not uncommon in Sudan where there is a high rate of consanguinity. Many cases are likely missed because of variable presentation and lack of public and professionals' awareness. This is the first series to describe this condition from Sub-Saharan Africa.

Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention.

OBJECTIVE: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS:  This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. RESULTS: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. CONCLUSION: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles.

Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice.

CONTEXT: Currently, the outcomes of the use of cisplatin in cancer therapy is limited by nephrotoxicity. OBJECTIVE: This study aims to investigate the nephroprotective role of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. MATERIALS AND METHODS: Adult female Wistar Albino mice were divided into eight groups (n = 8). Group I served as normal control. Groups II, III and IV received apigenin (3 mg/kg, i.p.), myricetin (3 mg/kg, i.p.) or their combination respectively, for seven days. Group V served as positive control group, received vehicles for seven days and cisplatin (7.5 mg/kg, i.p.) for three days starting at day five. Groups VI, VII and VIII received apigenin, myricetin or their combination, respectively for seven days as well as cisplatin injection for three days starting at day five. by the end of the experimental period, a biochemical study involving, nephrotoxicity markers [serum creatinine (Cr) and blood urea nitrogen (BUN)], apoptotic marker [caspase 3], inflammatory mediators [tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase I and II (COXI, COXII)] and oxidative stress biomarkers [malondialdehyde (MDA), reduced glutathione (GSH) and catalase] was conducted. In addition, renal histopathological alterations were evaluated. RESULTS: Apigenin, myricetin and their combination significantly reduced blood BUN, serum Cr, caspase-3TNF-α, IL-6, COXI and COXII, MDA levels and significantly increased GSH level and catalase activity parallel to, histopathological improvement in kidney tissues. DISCUSSION AND CONCLUSION: Apigenin and myricetin exhibited a protective and promising preventive strategy against cisplatin-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

Preoperative ripening of the cervix before operative hysteroscopy.

BACKGROUND: Hysteroscopy is an operation in which the gynaecologist examines the uterine cavity using a small telescopic instrument (hysteroscope) inserted via the vagina and the cervix. Almost 50% of hysteroscopic complications are related to difficulty with cervical entry. Potential complications include cervical tears, creation of a false passage, perforation, bleeding, or simply difficulty in entering the internal os (between the cervix and the uterus) with the hysteroscope. These complications may possibly be reduced with adequate preparation of the cervix (cervical ripening) prior to hysteroscopy. Cervical ripening agents include oral or vaginal prostaglandin, which can be synthetic (e.g misoprostol) or natural (e.g. dinoprostone) and vaginal osmotic dilators, which can be naturally occurring (e.g. laminaria) or synthetic. OBJECTIVES: To determine whether preoperative cervical preparation facilitates cervical dilatation and reduces the complications of operative hysteroscopy in women undergoing the procedure for any condition. SEARCH METHODS: In August 2014 we searched sources including the Menstrual Disorders and Subfertility Group (MDSG) Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and reference lists of relevant articles. We searched for published and unpublished studies in any language. SELECTION CRITERIA: Two review authors independently selected randomised controlled trials (RCTs) of cervical ripening agents used before operative hysteroscopy in pre- and postmenopausal women. Cervical ripening agents could be compared to each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were conducted independently by two review authors. The primary review outcomes were effectiveness of cervical dilatation (defined as the proportion of women requiring mechanical cervical dilatation) and intraoperative complications. Secondary outcomes were mean time required to dilate the cervix, preoperative pain, cervical width, abandonment of the procedure, side effects of dilating agents and duration of surgery. We calculated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% confidence intervals ( CIs). Data were statistically pooled where appropriate. Heterogeneity was assessed using the I(2) statistic. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Nineteen RCTs with a total of 1870 participants were included. They compared misoprostol with no treatment or placebo, dinoprostone or osmotic dilators.Misoprostol was more effective for cervical dilatation than placebo or no intervention, with fewer women requiring mechanical dilatation (OR 0.08, 95% CI 0.04 to 0.16, five RCTs, 441 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 80% of women undergoing hysteroscopy require mechanical dilatation without use of preoperative ripening agents, use of misoprostol will reduce the need for mechanical dilatation to between 14% and 39%. Misoprostol was associated with fewer intraoperative complications (OR 0.37, 95% CI 0.18 to 0.77, 12 RCTs, 901 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 3% of women undergoing hysteroscopy experience intraoperative complications without use of preoperative ripening agents, use of misoprostol will reduce the risk of complications to 2% or less.When specific complications were considered, the misoprostol group had a lower rate of cervical laceration or tearing (OR 0.25, 95% CI 0.11 to 0.57, nine RCTS, 669 women, I(2)=0%, moderate quality evidence) or false track formation (OR 0.34, 95% CI 0.12 to 0.97, seven RCTs, 560 participants, I(2)=0%, moderate quality evidence). There was no evidence of a difference between the groups in rates of uterine perforation (0.42, 95% CI 0.13 to 1.38, seven RCTs, 455 participants, I(2)=0%, low quality evidence) or uterine bleeding (OR 0.51, 95% CI 0.10 to 2.49, four RCTs, 340 participants, I(2)=0%, low quality evidence). Some treatment side effects (mild abdominal pain, vaginal bleeding, and increased body temperature) were more common in the misoprostol group.Compared with dinoprostone, misoprostol was associated with more effective cervical dilatation, with fewer women requiring mechanical dilatation (OR 0.58; 95% CI 0.34 to 0.98; one RCT, 310 participants, low quality evidence) and with fewer intraoperative complications (OR 0.32; 95% CI 0.12 to 0.83, one RCT, 310 participants, low quality evidence). However treatment side effects were more common in the misoprostol arm.Compared to osmotic dilatation (laminaria), misoprostol was associated with less effective cervical dilatation, with more women in the misoprostol group requiring mechanical dilatation (OR 5.96, 95% CI 2.61 to 13.59, one RCT, 110 participants, low quality evidence). There was no evidence of a difference between misoprostol and osmotic dilators in intraoperative complication rates (OR 5.14, 95% CI 0.24 to 109.01, three RCTs, 354 participants, low quality evidence), with only two events reported altogether.The overall quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods. AUTHORS' CONCLUSIONS: There is moderate quality evidence that use of misoprostol for preoperative ripening of the cervix before operative hysteroscopy is more effective than placebo or no treatment and is associated with fewer intraoperative complications such as lacerations and false tracks. However misoprostol is associated with more side effects, including preoperative pain and vaginal bleeding. There is low quality evidence to suggest that misoprostol has fewer intraoperative complications and is more effective than dinoprostone.There is also low quality evidence to suggest that laminaria may be more effective than misoprostol, with uncertain effects for complication rates. However the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days.

Knowledge, attitude, and practices of infertility among Saudi couples.

INTRODUCTION: Infertility places a huge psychological burden on infertile couples, especially for women. Greater knowledge of the factors affecting fertility may help to decrease the incidence of infertility by allowing couples to avoid certain risk factors. The aim of our study was (1) to assess the knowledge and attitudes of infertile and fertile Saudi participants on infertility, possible risk factors, and social consequences; and (2) to determine the practices of infertile Saudi couples to promote their fertility before having them attend an in vitro fertilization (IVF) clinic. METHODS AND MATERIALS: We conducted a cross-sectional study on 277 fertile participants from outpatient clinics and 104 infertile patients from the IVF clinic at King Abdulaziz Medical City between June 24, 2012 and July 4, 2012, using a previously validated interview questionnaire. Descriptive and analytical statistics were applied with a significance threshold of P ≤ 0.05. RESULTS: A generally poor level of knowledge (59%) and a neutral attitude (76%) toward infertility were reported by participants. Mistaken beliefs commonly held by the study participants regarding the causes of infertility were Djinns and supernatural causes (58.8%), black magic (67.5%), intrauterine devices (71.3%), and contraceptive pills (42.9%). The healer/Sheikh was reported as the primary and secondary preference for infertility treatment by 6.7% and 44.2% of IVF patients, respectively. Compared with fertile patients, IVF patients were significantly less likely to favor divorce (38.5% versus 57.6%; P = 0.001) or marriage to a second wife (62.5% versus 86.2%; P < 0.001), if the woman could not have a baby. The patients with infertility had more favorable attitudes toward fertility drugs (87.5% versus 68.4%; P = 0.003) and having a test tube baby (92.4% versus 70.3%; P < 0.001). Child adoption was accepted as an option for treatment by the majority of IVF patients (60.6%) and fertile outpatients (71.5%). Alternative treatments previously practiced by the IVF patients to improve fertility include practicing Ruqia (61%), using alternative medicine (42%), engaging in physical exercise (39%), eating certain foods (22%), and quitting smoking (12%). CONCLUSION: These findings have implications for health care providers regarding the reluctance that couples experiencing fertility problems may have, at least initially, to accept some interventions required for the couple to conceive.

Hormone therapy for endometriosis and surgical menopause.

BACKGROUND: Endometriosis is characterized by the presence of ectopic endometrial tissue that might lead to many distressing and debilitating symptoms. Despite available studies supporting standard hormone therapy for women with endometriosis and post-surgical menopause, there is still a concern that estrogens may induce a recurrence of the disease and its symptoms. OBJECTIVES: This review aimed to look at pain and disease recurrence in women with endometriosis who used hormone therapy for post-surgical menopause. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialized Register (March 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), and references lists of articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled trials studying hormone therapy for women with endometriosis in post-surgical menopause. DATA COLLECTION AND ANALYSIS: Review authors assessed the eligibility of trials and their quality. MAIN RESULTS: Two studies fulfilled our inclusion criteria. One trial compared the nonstop transdermal application of 17beta-estradiol (0.05 mg/day) combined with cyclic medroxy progesterone acetate (10 mg per day) for 12 days per month in women with a conserved uterus with nonstop tibolone (2.5 mg/day). The second trial used sequential administration of estrogens and progesterone with two 22 cm(2) patches applied weekly to produce a controlled release of 0.05 mg/day. Micronized progesterone was administered orally (200 mg/day) for 14 days with a 16-day interval free of treatment. Pain and dyspareunia The first trial reported recurrence of pain in the estrogen and progesterone arm in 4/10 of women compared with 1/11 in the tibilone arm. In the latter, 4/115 women reported recurrence of pain in the treatment group compared with 0/57 patients in the no-treatment arm. Neither finding was statistically different.Confirmed recurrence or exacerbation of endometriosis This outcome was not reported in the first trial. The second found that 2/115 of the treatment group developed recurrence of endometriosis with no recurrence reported in the no-treatment group. This was not statistically significant. No woman was re-operated on in the no-treatment group compared with 2/115 in the treatment group. AUTHORS' CONCLUSIONS: Hormone replacement therapy for women with endometriosis in post-surgical menopause could result in pain and disease recurrence. However, the evidence in the literature is not strong enough to suggest depriving severely symptomatic patients from this treatment. There is a need for more randomised controlled studies.