A Minimally Interventional Approach to Oesophageal Atresia Repair With Early Enteral Feeding is Safe, Optimises Neonatal Outcomes, and Reduces Resource use.

PURPOSE: Recent series of newborn Oesophageal Atresia (OA) repair continue to report widespread use of chest drains, gastrostomy, routine contrast studies and parenteral nutrition (PN) despite evidence suggesting these are superfluous. We report outcomes using a minimally interventional approach to post-operative recovery. METHODS: Ethically approved (15/WA/0153), single-centre, retrospective case-note review of consecutive infants with OA 2000-2022. Infants with OA and distal trache-oesophageal fistula undergoing primary oesophageal anastomosis at initial surgery were included (including those with comorbidities such as duodenal atresia, anorectal malformation and cardiac lesions). Our practice includes routine use of a trans-anastomotic tube (TAT), no routine chest drain nor gastrostomy, early enteral and oral feeding, no routine PN and no routine contrast study. Data are median (IQR). RESULTS: Of total 186 cases of OA treated during the time period, 157 met the inclusion criteria of which 2 were excluded as casenotes unavailable. TAT was used in 150 infants. A chest drain was required in 13 (8%) and two infants had a neonatal gastrostomy. Enteral feeds were started on postoperative day 2 (2-3), full enteral feeds established by day 4 (4-6) and oral feeds started on day 5 (4-8). PN was required in 15%. Median postoperative length of stay was 10 days (8-17). Progress was quicker in term infants than preterm. One infant died of cardiac disease prior to neonatal discharge. Two planned post-operative contrast studies were performed (surgeon preference) and a further 7 due to clinical suspicion of anastomotic leak. Contrast study was therefore avoided in 94%. There were 2 anastomotic leaks; both presented clinically at day 4 and day 8 after oral feeds had been started. CONCLUSION: Our minimally interventional approach is safe. It facilitates prompt recovery with lower resource use, reduced demand on nursing staff, reduced radiation burden, and early discharge home compared to published series without adversely affecting outcomes. LEVEL OF EVIDENCE: Level 4.

Ex-chitin-g news on drug-induced fungal epitope unmasking.

The microbial cell wall is an essential cellular organelle commonly targeted by antimicrobials. It is also a battleground of innate immune recognition where microbes can evade immune recognition by masking essential cell wall components. A recent study (A. S. Wagner, S. W. Lumsdaine, M. M. Mangrum, and T. B. Reynolds, mBio https://doi.org/10.1128/mbio.00074-23, 2023) provides insight into how echinocandin antifungals cause exposure of proinflammatory ß(1,3)-glucan by driving excess chitin production in the weakened cell wall. Although many environmental and biological activities perturb cell wall integrity and regulate ß(1,3)-glucan exposure, we still know little about which intracellular signaling components regulate the cell wall changes that result in disrupted cell wall architecture. Wagner et al. showed that calcineurin and the Mkc1p kinase regulate chitin deposition and ß(1,3)-glucan unmasking. They further identified chitin synthesis as a key driving force in cell wall structure disruption leading to epitope exposure. Their findings highlight how fungal cell wall dynamics have important implications for antifungal immunity and future drug development.

A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis-Associated Strains.

Vulvovaginal candidiasis (VVC) affects nearly 3/4 of women during their lifetime, and its symptoms seriously reduce quality of life. Although Candida albicans is a common commensal, it is unknown if VVC results from a switch from a commensal to pathogenic state, if only some strains can cause VVC, and/or if there is displacement of commensal strains with more pathogenic strains. We studied a set of VVC and colonizing C. albicans strains to identify consistent in vitro phenotypes associated with one group or the other. We find that the strains do not differ in overall genetic profile or behavior in culture media (i.e., multilocus sequence type [MLST] profile, rate of growth, and filamentation), but they show strikingly different behaviors during their interactions with vaginal epithelial cells. Epithelial infections with VVC-derived strains yielded stronger fungal proliferation and shedding of fungi and epithelial cells. Transcriptome sequencing (RNA-seq) analysis of representative epithelial cell infections with selected pathogenic or commensal isolates identified several differentially activated epithelial signaling pathways, including the integrin, ferroptosis, and type I interferon pathways; the latter has been implicated in damage protection. Strikingly, inhibition of type I interferon signaling selectively increases fungal shedding of strains in the colonizing cohort, suggesting that increased shedding correlates with lower interferon pathway activation. These data suggest that VVC strains may intrinsically have enhanced pathogenic potential via differential elicitation of epithelial responses, including the type I interferon pathway. Therefore, it may eventually be possible to evaluate pathogenic potential in vitro to refine VVC diagnosis. IMPORTANCE Despite a high incidence of VVC, we still have a poor understanding of this female-specific disease whose negative impact on women's quality of life has become a public health issue. It is not yet possible to determine by genotype or laboratory phenotype if a given Candida albicans strain is more or less likely to cause VVC. Here, we show that Candida strains causing VVC induce more fungal shedding from epithelial cells than strains from healthy women. This effect is also accompanied by increased epithelial cell detachment and differential activation of the type I interferon pathway. These distinguishing phenotypes suggest it may be possible to evaluate the VVC pathogenic potential of fungal isolates. This would permit more targeted antifungal treatments to spare commensals and could allow for displacement of pathogenic strains with nonpathogenic colonizers. We expect these new assays to provide a more targeted tool for identifying fungal virulence factors and epithelial responses that control fungal vaginitis.

Clinical law: what do clinicians want to know? The demography of clinical law.

This is the first description of the questions that clinicians ask a department of clinical law, relating to the legal rules applicable to the care of their patients. OBJECTIVES: To describe in detail the demography of clinical legal enquiries made by clinicians of all professions concerning the care of their patients. To collate and categorise the varieties of enquiry, to identify phenotypic patterns. To provide colleges, regulators, commissioners, educators and the NHS with an insight into hitherto undescribed subject matter, better to understand and respond to this aspect of clinical practice. DESIGN: Prospective collection of all clinical legal referrals recorded in writing over 12 years by a department of clinical law. SETTING: An English Tertiary Hospital NHS Trust. PARTICIPANTS: Clinical staff of the regulated professions, all seeking to have their clinical legal enquiries answered. MAIN OUTCOME MEASURES: The description of the demography of clinical law. RESULTS: 1251 written records were identified and reviewed. These were divided into nine broad clinical legal subject areas (domains): mental disorders, parents and children, incapacity, consent for treatment, disclosure of private information, other statutory, regulated practice, professional practice, clinical practice. Within these, 149 clinical legal phenotypes were identified to which each case could be assigned. CONCLUSIONS: Among a broad range of enquiries, recognisable clinical legal phenotypes exist and have for the first time been described and categorised. These are clinical situations which clinicians need to be able to recognise and equipped to deal with. Doing so will likely facilitate timely and better treatment.

A Case of Prepubertal Ovarian Tissue Cryopreservation in Metachronous Bilateral Mature Ovarian Teratoma Requiring Bilateral Oophorectomy.

Mature ovarian teratoma has the potential to occur metachronously in the contralateral ovary. There are significant implications for fertility as bilateral oophorectomy may be indicated. In prepubertal girls, ovarian tissue cryopreservation (OTC) offers the only possibility of a future biological pregnancy but outcome data are limited. We present a case of prepubertal OTC in a 12-year-old girl undergoing a second oophorectomy for metachronous contralateral mature teratoma. We offer a discussion of the challenges that emerged regarding perioperative decision-making, balancing the need for safe oncological resection with the desire to preserve fertility.