A proposed difficulty grading system for laparoscopic bile duct exploration: benefits to clinical practice, training and research.

BACKGROUND: A gap remains between the mounting evidence for single session management of bile duct stones and the adoption of this approach. Laparoscopic bile duct exploration (LBDE) is limited by the scarcity of training opportunities and adequate equipment and by the perception that the technique requires a high skill-set. The aim of this study was to create a new classification of difficulty based on operative characteristics and to stratify postoperative outcomes of easy vs. difficult LBDE irrespective of the surgeon's experience. METHODS: A cohort of 1335 LBDEs was classified according to the location, number and size of ductal stones, the retrieval technique, utilisation of choledochoscopy and specific biliary pathologies encountered. A combination of features indicated easy (Grades I and II A & B) or difficult (Grades III A and B, IV and V) transcystic or transcholedochal explorations. RESULTS: 78.3% of patients with acute cholecystitis or pancreatitis, 37% with jaundice and 46% with cholangitis had easy explorations. Difficult explorations were more likely to present as emergencies, with obstructive jaundice, previous sphincterotomy and dilated bile ducts on ultrasound scans. 77.7% of easy explorations were transcystic and 62.3% of difficult explorations transductal. Choledochoscopy was utilised in 23.4% of easy vs. 98% of difficult explorations. The use of biliary drains, open conversions, median operative time, biliary-related complications, hospital stay, readmissions, and retained stones increased with the difficulty grade. Grades I and II patients had 2 or more hospital episodes in 26.5% vs. 41.2% for grades III to V. There were 2 deaths in difficulty Grade V and one in Grade IIB. CONCLUSION: Difficulty grading of LBDE is useful in predicting outcomes and facilitating comparison between studies. It ensures fair structuring and assessment of training and progress of the learning curve. LBDEs were easy in 72% with 77% completed transcystically. This may encourage more units to adopt this approach.

Operative Difficulty, Morbidity and Mortality Are Unrelated to Obesity in Elective or Emergency Laparoscopic Cholecystectomy and Bile Duct Exploration.

OBJECTIVES: The challenges posed by laparoscopic cholecystectomy (LC) in obese patients and the methods of overcoming them have been addressed by many studies. However, no objective tool of reporting operative difficulty was used to adjust the outcomes and compare studies. The aim of this study was to establish whether obesity adds to the difficulty of LC and laparoscopic common bile duct exploration (LCBDE) and affects their outcomes on a specialist biliary unit with a high emergency workload. METHODS: A prospectively maintained database of 4699 LCs and LCBDEs performed over 19 years was analysed. Data of patients with body mass index (BMI) ≥ 35, defined as grossly obese, was extracted and compared to a control group. RESULTS: A total of 683 patients (14.5%) had a mean BMI of 39.9 (35-63), of which 63.4% met the definition of morbidly obese. They had significantly more females and significantly higher ASA II classifications. They had equal proportions of emergency admissions, similar incidence of operative difficulty grades 4 or 5 and no open conversions and were less likely to undergo LCBDE than non-obese patients. There were no significant differences in median operative times, morbidity, readmission or mortality rates. CONCLUSIONS: This study, the first to classify gall stone surgery in obese patients according to operative difficulty grading, showed no difference in complexity when compared to the non-obese. Refining access and closure techniques is key to avoiding difficulties. Index admission surgery for biliary emergencies prevents multiple admissions with potential complications and should not be denied due to obesity.

The incidence, operative difficulty and outcomes of staged versus index admission laparoscopic cholecystectomy and bile duct exploration for all comers: a review of 5750 patients.

BACKGROUND: The timing of laparoscopic cholecystectomy (LC) for emergency biliary admissions remains inconsistent with national and international guidelines. The perception that LC is difficult in acute cholecystitis and the popularity of the two-session approach to pancreatitis and suspected choledocholithiasis result in delayed management. METHODS: Analysis of prospectively maintained data in a unit adopting a policy of "intention to treat" during the index admission. The aim was to study the incidence of previous biliary admissions and compare the operative difficulty, complications and postoperative outcomes with patients who underwent index admission LC. RESULTS: Of the 5750 LC performed, 20.8% had previous biliary episodes resulting in one admission in 93% and two or more in 7%. Most presented with biliary colic (39.6%) and acute cholecystitis (27.6%). A previous biliary history was associated with increased operative difficulty (p < 0.001), longer operating times (86.9 vs. 68.1 min, p < 0.001), more postoperative complications (7.8% vs. 5.4%, p = 0.002) and longer hospital stay (8.1 vs. 5.5 days, p < 0.001) and presentation to resolution intervals. However, conversion and mortality rates showed no significant differences. CONCLUSION: Index admission LC is superior to interval cholecystectomy and should be offered to all patients fit for general anaesthesia regardless of the presenting complaints. Subspecialisation should be encouraged as a major factor in optimising resource utilisation and postoperative outcomes of biliary emergencies.

Naturally Occurring Chromone Glycosides: Sources, Bioactivities, and Spectroscopic Features.

Chromone glycosides comprise an important group of secondary metabolites. They are widely distributed in plants and, to a lesser extent, in fungi and bacteria. Significant biological activities, including antiviral, anti-inflammatory, antitumor, antimicrobial, etc., have been discovered for chromone glycosides, suggesting their potential as drug leads. This review compiles 192 naturally occurring chromone glycosides along with their sources, classification, biological activities, and spectroscopic features. Detailed biosynthetic pathways and chemotaxonomic studies are also described. Extensive spectroscopic features for this class of compounds have been thoroughly discussed, and detailed 13C-NMR data of compounds 1-192, have been added, except for those that have no reported 13C-NMR data.

Rates of Bile Acid Diarrhoea After Cholecystectomy: A Multicentre Audit.

INTRODUCTION: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation, e.g. following cholecystectomy. Post-cholecystectomy diarrhoea has been reported in 2.1-57.2% of patients; however, this is not necessarily due to BAD. The aim of this study was to determine the rates of bile acid diarrhoea diagnosis after cholecystectomy and to consider investigation practices. METHODS: A retrospective analysis of electronic databases from five large centres detailing patients who underwent laparoscopic cholecystectomy between 2013 and 2017 was cross-referenced with a list of patients who underwent 75SeHCAT testing. A 7-day retention time of <15% was deemed to be positive. Patient demographics and time from surgery to investigation were collected and compared for significance (p < 0.05). RESULTS: A total of 9439 patients underwent a laparoscopic cholecystectomy between 1 January 2013 and 31 December 2017 in the five centres. In total, 202 patients (2.1%) underwent investigation for diarrhoea via 75SeHCAT, of which 64 patients (31.6%) had a 75SeHCAT test result of >15%, while 62.8% of those investigated were diagnosed with bile acid diarrhoea (BAD). In total, 133 (65.8%) patients also underwent endoscopy and 74 (36.6%) patients had a CT scan. Median time from surgery to 75SeHCAT test was 672 days (SD ± 482 days). DISCUSSION/CONCLUSION: Only a small proportion of patients, post-cholecystectomy, were investigated for diarrhoea with significant time delay to diagnosis. The true prevalence of BAD after cholecystectomy may be much higher, and clinicians need to have an increased awareness of this condition due to its amenability to treatment. 75SeHCAT is a useful tool for diagnosis of bile acid diarrhoea.

Detection of polymorphism within leptin gene in Egyptian river buffalo and predict its effects on different molecular levels.

BACKGROUND: Leptin (LEP) regulates the glucose homeostasis directly and centrally by the regulation of the insulin levels or indirectly by alternation of the levels of the other glucose metabolism regulator hormones. The present investigation studied the polymorphism in LEP gene which is related to fertility in 81 female Egyptian river buffalo. RESULTS: The PCR-RFLP pattern of the gene using the restriction enzyme Eco91I showed that all the animals had monomorphic pattern in the studied gene which consists of CC. A 511-bp fragment from LEP gene was amplified and sequenced. The homology between the amplified LEP gene fragment in buffalo and cattle, sheep, goat, human, and mouse on the nucleotides sequence level was 99, 97, 97, 87, and 79%, respectively, and on the translated amino acids sequence level was 100, 98, 98, 85, and 82%, respectively. Several SNPs were detected; among them, the T27C SNP disrupted an intronic splicing silencer. The A114G, A310G, G263A, and G379A SNPs disrupt exonic splicing enhancers, and the last two SNPs create new exonic splicing enhancers. The A114G, C163A, A211G, G288A, A310G, A322G, G330C, C348T, T360C, and G379A SNPs cause S71G, T87 N, N103S, E129K, E136G, Y140C, E143Q, R149W, S153P, and R159Q amino acids mutations. N103S, E129K, E136G, Y140C, E143Q, and S153P were classified as deleterious mutations. Y140, E143, N103, and R149 were the most conserved among the mutated amino acids. S71G only increased the stability of the leptin protein while the remaining mutations decreased it. CONCLUSION: Four SNPs were revealed among the tested animals. Twenty-one SNPs were found between the sequenced amplicon and the buffalo records in the Genbank. Some SNPs were predicted to have several effects on different biological processes like mRNA splicing, protein stability, and the gene functions.

Anti-Müllerian hormone levels in patients with turner syndrome: Relation to karyotype, spontaneous puberty, and replacement therapy.

Most girls with Turner syndrome (TS) suffer from incomplete sexual development, premature ovarian failure, and infertility due to abnormal ovarian folliculogenesis. Serum anti-Müllerian hormone (AMH) levels reflect the ovarian reserve in females, even in childhood. Thus, we aimed to assess serum AMH levels in girls with TS and its relation to karyotype, spontaneous puberty, and growth hormone (GH) therapy. Fifty TS were compared to 50 age- and sex-matched controls. All subjects were subjected to history, anthropometric assessment, Tanner pubertal staging and measurement of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and AMH. Karyotype results were obtained from patients' records. Serum AMH was measurable in 12 TS patients (24%). The lowest frequency of measurable AMH was in patients with a karyotype of 45,X. The measurable AMH was associated with spontaneous breast development (p = .003) and spontaneous menarche (p = .001). AMH correlated negatively with FSH (r = -.846, p = .000) and LH (r = -.83, p = .034). GH therapy increased the odds of having measurable AMH in TS girls (p = .002). In conclusion, AMH was associated with karyotype, spontaneous pubertal development, LH, and FSH in TS girls and may serve as a useful marker of ovarian function and ongoing follicular development in prepuberty.

Vitamin D status in prepubertal children with isolated idiopathic growth hormone deficiency: effect of growth hormone therapy.

Few studies, and with controversial results, analyzed vitamin D status in children before and after growth hormone (GH) treatment. Thus, we aimed to assess vitamin D status in prepubertal children with idiopathic growth hormone deficiency (GHD), and to evaluate the effect of GHD and GH treatment on vitamin D levels. Fifty prepubertal children with isolated GHD were compared with 50 controls. All were subjected to history, anthropometric assessment and measurement of 25 hydroxyvitamin D (25(OH)D), serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone (PTH) at diagnosis and 1 year after GH therapy. Serum 25(OH)D levels <30 ng/mL and 20 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. 25(OH)D was lower in cases than controls. Forty per cent of children with GHD were 25(OH)D insufficient and 44% deficient, while 16% were sufficient at baseline. There was a positive correlation between 25(OH)D and peak GH levels. Peak GH was a significant predictor of 25(OH)D levels. After 1 year of GH therapy, 25(OH)D increased (18.42±5.41 vs 34.5±10.1 ng/mL; P<0.001). Overall, 22% of cases remained insufficient and 24% deficient, with an increase in prevalence of children with normal levels (54%; P<0.001). 25(OH) correlated negatively with PTH (r=-0.71, P=0.01). In conclusion, hypovitaminosis D is prevalent in children with GHD and significantly improved 1 year after GH therapy. 25(OH)D should be assessed in children with GHD at diagnosis and during follow-up.

Uniportal VATS for treatment of bullous lung disease.

This tutorial shows the resection of a bulla by uniportal video assisted thoracoscopic surgery in bullous lung disease. This disease is a benign condition requiring treatment in cases of severe dyspnea, spontaneous secondary pneumothorax, repeated infection, hemoptysis, and an increase in bulla size. The uniportal VATS approach results in less pain, better cosmoses, and a quicker recovery for the patient.

Iodine deficiency in Egyptian autistic children and their mothers: relation to disease severity.

BACKGROUND AND AIMS: Because autism may be a disease of early fetal brain development, maternal hypothyroxinemia (HT) in early pregnancy secondary to iodine deficiency (ID) may be related to etiology of autism. The aim of the study was to assess the iodine nutritional status in Egyptian autistic children and their mothers and its relationship with disease characteristics. METHODS: Fifty autistic children and their mothers were studied in comparison to 50 controls. All subjects were subjected to clinical evaluation, measurement of urinary iodine (UI), free triiodothyronine (fT3), free tetraiodothyronine (fT4) and thyroid-stimulating hormone (TSH) along with measurement of thyroid volume (TV). In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children. RESULTS: Of autistic children and their mothers, 54% and 58%, respectively, were iodine deficient. None of the control children or their mothers was iodine deficient. UI was lower among autistic patients (p <0.001) and their mothers (p <0.001). Childhood Autism Rating Scale (CARS) score correlated negatively with UI (r = -0.94, p <0.001). Positive correlations were detected between autistic patients and their mothers regarding UI (r = 0.88, p <0.001), fT3 (r = 0.79, p = 0.03), fT4 (r = 0.91, p <0.001) and TSH (r = 0.69, p = 0.04). Autism had a significant risk for association with each of low UI (OR: 9.5, 95% CI: 2.15-33.8, p = 0.02) and intake of noniodized salt (OR: 6.82, 95% CI = 1.36-34.27, p = 0.031). CONCLUSIONS: ID is prevalent in Egyptian autistic children and their mothers and was inversely related to disease severity and could be related to its etiology.

Effect of zinc supplementation on growth hormone-insulin growth factor axis in short Egyptian children with zinc deficiency.

BACKGROUND: The relationship between zinc (Zn) and growth hormone-insulin growth factor (GH-IGF) system and how Zn therapy stimulates growth in children has not been clearly defined in humans. Thus, we aimed to assess GH-IGF axis in short children with Zn deficiency and to investigate the effect of Zn supplementation on these parameters. METHODS: Fifty pre-pubertal Egyptian children with short stature and Zn deficiency were compared to 50 age-, sex-, and pubertal stage- matched controls. All subjects were subjected to history, auxological assessment and measurement of serum Zn, IGF-1, insulin growth factor binding protein-3 (IGFBP-3); and basal and stimulated GH before and 3 months after Zn supplementation (50 mg/day). RESULTS: After 3 months of Zn supplementation in Zn-deficient patients, there were significant increases in height standard deviation score (SDS, P = 0.033), serum Zn (P < 0.001), IGF-1 (P < 0.01), IGF-1 standard deviation score (SDS, P < 0.01) and IGFBP-3 (P = 0.042). Zn rose in all patients but reached normal ranges in 64 %, IGF-1 levels rose in 60 % but reached normal ranges in 40 % and IGFBP-3 levels rose in 40 % but reached reference ranges in 22 %. Growth velocity (GV) SDS did not differ between cases and controls (p = 0.15) but was higher in GH-deficient patients than non-deficient ones, both having Zn deficiency (p = 0.03). CONCLUSION: Serum IGF-1 and IGFBP-3 levels were low in short children with Zn deficiency, and increased after Zn supplementation for 3 months but their levels were still lower than the normal reference ranges in most children; therefore, Zn supplementation may be necessary for longer periods.

Reduction of spermatogenesis but not fertility in Creb3l4-deficient mice.

Creb3l4 belongs to the CREB/ATF family of transcription factors that are involved in mediating transcription in response to intracellular signaling. This study shows that Creb3l4 is expressed at low levels in all organs and in different stages of embryogenesis but is present at very high levels in the testis, particularly in postmeiotic male germ cells. In contrast to CREB3L4 in the human prostate, of which specific expression was detected, Creb3l4 transcripts in the mouse prostate could be detected only by RT-PCR. To identify the physiological function of Creb3l4, the murine gene was inactivated by replacement with the gene encoding green fluorescent protein. Surprisingly, Creb3l4-deficient mice were born at expected ratios, were healthy, and displayed normal long-term survival rates. Despite a significant reduction in the number of spermatozoa in the epididymis of Creb3l4(-)(/)(-) mice, the breeding of mutant males with wild-type females was productive and the average litter size was not significantly altered in comparison to wild-type littermates. Further analyses revealed that the seminiferous tubules of Creb3l4(-)(/)(-) mice contained all of the developmental stages, though there was evidence for increased apoptosis of meiotic/postmeiotic germ cells. These results suggest that Creb3l4 plays a role in male germ cell development, but its loss is insufficient to completely compromise the production of spermatozoa.

Disruption of the pelota gene causes early embryonic lethality and defects in cell cycle progression.

Mutations in either the Drosophila melanogaster pelota or pelo gene or the Saccharomyces cerevisiae homologous gene, DOM34, cause defects of spermatogenesis and oogenesis in Drosophila, and delay of growth and failure of sporulation in yeast. These phenotypes suggest that pelota is required for normal progression of the mitotic and meiotic cell cycle. To determine the role of the pelota in mouse development and progression of cell cycle, we have established a targeted disruption of the mouse PELO: Heterozygous animals are variable and fertile. Genotyping of the progeny of heterozygous intercrosses shows the absence of Pelo(-/-) pups and suggests an embryo-lethal phenotype. Histological analyses reveal that the homozygous Pelo deficient embryos fail to develop past day 7.5 of embryogenesis (E7.5). The failure of mitotic active inner cell mass of the Pelo(-/-) blastocysts to expand in growth after 4 days in culture and the survival of mitotic inactive trophoplast indicate that the lethality of Pelo-null embryos is due to defects in cell proliferation. Analysis of the cellular DNA content reveals the significant increase of aneuploid cells in Pelo(-/-) embryos at E7.5. Therefore, the percent increase of aneuploid cells at E7.5 may be directly responsible for the arrested development and suggests that Pelo is required for the maintenance of genomic stability.