Mining for antifungal agents to inhibit biofilm formation of Candida albicans: A study on green synthesis, antibiofilm, cytotoxicity, and in silico ADME analysis of 2-amino-4H-pyran-3-carbonitrile derivatives.

Candida albicans (C. albicans) biofilm infections are quite difficult to manage due to their resistance against conventional antifungal drugs. To address this issue, there is a desperate need for new therapeutic drugs. In the present study, a green and efficient protocol has been developed for the synthesis of 2-amino-4H-pyran-3-carbonitrile scaffolds 4a-i, 6a-j, and 8a-g by Knoevenagel-Michael-cyclocondensation reaction between aldehydes, malononitrile, and diverse enolizable C-H activated acidic compounds using guanidinium carbonate as a catalyst either under grinding conditions or by stirring at room temperature. This protocol is operationally simple, rapid, inexpensive, has easy workup and column-free purification. A further investigation of the synthesized compounds was conducted to examine their antifungal potential and their ability to inhibit the growth and development of biofilm-forming yeasts like fungus C. albicans. According to our findings, 4b, 4d, 4e, 6e, 6f, 6g, 6i, 8c, 8d, and 8g were found to be active and potential inhibitors for biofilm infection causing C. albicans. The inhibition of biofilm by active compounds were observed using field emission scanning electron microscopy (FESEM). Biofilm inhibiting compounds were also tested for in vitro toxicity by using 3T3-L1 cell line, and 4b, 6e, 6f, 6g, 6i, 8c, and 8d were found to be biocompatible. Furthermore, the in silico ADME descriptors revealed drug-like properties with no violation of Lipinski's rule of five. Hence, the result suggested that synthesized derivatives could serve as a useful aid in the development of novel antifungal compounds for the treatment of fungal infections and virulence in C. albicans.

Peritoneal lavage during laparoscopic appendectomy for complex appendicitis is associated with increased post-operative morbidity.

Aim: Appendicitis is one of the most common paediatric surgical pathologies seen by paediatric surgeons worldwide. Laparoscopic appendectomy is undertaken for all cases of appendicitis in our institute. Intraperitoneal lavage following appendectomy is the conventional way of managing complicated appendicitis; however, some surgeons debate the efficacy of this practice. The aim of this study was to compare outcomes of intraperitoneal lavage versus suction only in children with complicated appendicitis. Methods: Data were collected retrospectively between January 2018 and January 2019. All patients undergoing laparoscopic appendectomy for complex appendicitis were included and divided into two groups, patients who had suction only and those who had lavage and suction. Outcome parameters studied were the length of stay (LOS), number of temperature spikes > 37.7 (TS), operative times (OT) and readmission for intra-abdominal collections. Comparison between the two groups was performed using two sample t-test with unequal variance, significance was set at P < 0.05. Results: A total of 115 patients were included (lavage n = 52, Suction n = 63). The LOS (P = 0.0054), TS (0.0109), OT (P < 0.0001) were significantly higher in the lavage group compared to the suction-only group. Overall rates of readmission were similar between groups, however, readmission for the confirmed intra-abdominal collection was more common in the lavage group. Conclusion: Based on our study, it appears that there is no advantage in performing an intraperitoneal lavage for complex appendicitis. It resulted in a prolonged stay, more post-operative TS and longer operative duration. The likelihood of being readmitted with an intra-abdominal collection following a lavage was higher compared to suction only.

Efficacy of fibrin sealant as waterproof cover in improving outcome in hypospadias surgery.

BACKGROUND: This prospective comparative study aims to assess the efficacy of fibrin sealant to improve outcomes in paediatric patients operated for hypospadias. MATERIALS AND METHODS: Forty consecutive patients with hypospadias were randomised into two groups of twenty patients each. The first group underwent hypospadias repair, technique depending on the type of hypospadias, whereas in the second group, fibrin sealant was used to reinforce the urethroplasty. Assessment was done with respect to the type of hypospadias, type of repair done, operative time, immediate post-operative complications (early ooze and skin flap-related complications), intermediate complications (urethra-cutaneous fistula) and delayed post-operative complications (penile torsion and poor cosmetic outcome) at follow-up. We also compared the overall improvement in outcome among the two groups. RESULTS: First Group: The mean operative time was 1 h and 45 min. Complications were seen in nine patients: Early ooze (n = 2); skin flap-related complications (n = 3); fistula (n = 7); poor cosmetic outcome (n = 7) and penile torsion (n = 4). Second Group (Fibrin Sealant): The mean operative time was 1 h and 30 min. Post-operative complications were observed in five patients: Coronal fistula (n = 3) and poor cosmetic outcome (n = 3). On comparing, the differences in outcomes of ooze, skin flap-related complications and torsion were found to be statistically significant with P < 0.05. The differences in the urethra-cutaneous fistula and cosmetic appearance were not found to be statistically significant. The difference in overall improvement in complications was found to be statistically significant. CONCLUSION: Fibrin sealant, when applied over the urethroplasty suture line as a waterproof cover, may help to improve the outcome in patients with hypospadias.

Emergency scrotal exploration in children: Is it time for a change in mindset in the UK?

INTRODUCTION: Acute scrotal pain is a common problem in children. Amongst the various causes, only testicular torsion (TT) needs urgent, and arguably any, surgical intervention. However TT accounts for only approximately 25% of cases. The diagnosis of TT is currently based mainly on history and clinical examination in the UK. OBJECTIVE: We sought to find the incidence of finding TT during emergency scrotal exploration in four paediatric surgical centres in the UK. We also assessed the preoperative utilisation of clinical risk scores and Doppler ultrasound (DUS) to aid in the diagnosis. PATIENTS AND METHODS: A retrospective review of 50 consecutive scrotal explorations done for acute scrotal pain at four tertiary pediatric surgical centres in 2019, including the preoperative utilisation of DUS, was analysed. Additionally an online survey was also sent out to consultant members of the British Association of Paediatric Urology to gauge their threshold for exploration, use of preoperative investigations and incidence of finding TT in their practice. RESULTS: In the four UK centres reviewed, TT was found in 24.5% (SD = 8.54) of explorations. The overall utilisation of preoperative DUS was 10%. The online survey revealed a low threshold for exploration. However 72% of respondents recalled finding TT in <50% of explorations, with just over a third reporting finding TT in only 10% of explorations. There was low utilisation of preoperative DUS and clinical risk scores. DISCUSSION: The incidence of finding TT during exploration in this cohort is the same as the incidence of TT in a population of children presenting with acute scrotal pain. We hypothesise that this is due to low accuracy of clinical assessment, low utilisation of preoperative clinical and radiological aids and the practice of exploring torted testicular appendages. Improving awareness and training in these modalities will increase diagnostic accuracy, limiting emergency scrotal explorations to those children with a higher risk of testicular torsion. A care pathway for children presenting with acute scrotal pain is suggested () CONCLUSIONS: There is a low incidence of finding testicular torsion during paediatric scrotal explorations in the UK. There is low preoperative utilisation of clinical risk scores and Doppler ultrasound, which if utilised, could improve diagnostic accuracy.

Traumatic duodenal injury in children: A report of two cases.

Duodenal injury following blunt abdominal trauma in children is extremely rare. It commonly has a delayed presentation, thus leading to increased mortality and morbidity. We report two cases of isolated duodenal injury following blunt abdominal trauma in children.

Desmosis coli - a case report and review of the literature.

Desmosis coli is a rare pathology presenting as slow transit constipation. In this case we would like to discuss the presentation and management of desmosis coli. A 14-month-old female hailing from western India with a history of chronic constipation presented with acute massive abdominal distension and vomiting. At laparotomy, a hugely dilated transverse and sigmoid colon with a transition zone at the lower sigmoid was found. A transverse stoma was done after taking multiple sero-muscular biopsies. The patient underwent re-exploration on day 14 because of the non-functioning of the stoma and a fixed bowel loop. The histopathology report was suggestive of normal ganglion cells. Unfortunately, the stoma continued not to function. A dye study showed dye in the colon after 24 hours ruling out any anatomical obstruction. Histopathology slides were reviewed multiple times and reported lack of connective tissue of the colonic wall leading to the diagnosis of desmosis coli. The patient was started on gradual feeds and pro-kinetics and over the next 2 weeks the stoma started functioning slowly. Desmosis coli is a rare cause of constipation which should be suspected in cases where aganglionosis has been ruled out and the constipation is refractory to conventional therapy.

Fetus in Fetu: Two Cases and Literature Review.

Fetus in fetu is a rare cause of abdominal mass in infants wherein a parasitic twin grows inside a host. The true etiology is unclear. Various theories have been postulated. We report two cases of retroperitoneal fetus in fetu in female infants.