Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

Defining the safety of early ileostomy closure after ileal pouch anal anastomosis.

PURPOSE: The safety of early ileostomy reversal after ileal pouch anal anastomosis (IPAA) has not been established. Our hypothesis was that ileostomy reversal before 8 weeks is associated with negative outcomes. METHODS: This was a retrospective cohort study from a prospectively maintained institutional database. Patients who underwent primary IPAA with ileostomy reversal between 2000 and 2021 from a Pouch Registry were stratified on the basis of timing of reversal. Those reversed before 8 weeks (early) and those reversed from 8 weeks to 116 days (routine) were compared. The primary outcome was overall complications according to timing and reason for closure. RESULTS: Ileostomy reversal was performed early in 92 patients and routinely in 1908. Median time to closure was 49 days in the early group and 93 days in the routine group. Reasons for early reversal were stoma-related morbidity in 43.3% (n = 39) and scheduled closure in 56.7% (n = 51). The complication rate in the early group was 17.4% versus 11% in the routine group (p = 0.085). When early patients were stratified according to reason for reversal, those reversed early for stoma-related morbidity had an increased complication rate compared to the routine group (25.6% vs. 11%, p = 0.006). Patients undergoing scheduled reversal in the early group did not have increased complications (11.8% vs. 11%, p = 0.9). There was a higher likelihood of pouch anastomotic leak when reversal was performed early for stoma complications compared to routinely (OR 5.13, 95% CI 1.01-16.57, p = 0.049). CONCLUSIONS: Early closure is safe but could be delayed in stoma morbidity as patients may experience increased complications.

What is the real morbidity after emergency colectomy for Crohn's disease? A propensity score matched study.

BACKGROUND: In the inflammatory bowel disease literature, emergency surgery for Crohn's disease (CD) is associated with worse postoperative outcomes as compared to elective surgery. Previous studies have compared heterogeneous groups only. We hypothesized that this association would be lost after matched analysis. We aimed to compare matched CD patients undergoing elective vs emergency surgery. METHODS: The National Surgical Quality Improvement database (01/2005-12/2019) was utilized to identify adult CD surgical patients. Univariate and conditional logistic regression models were used to analyze unmatched and matched cohorts. Propensity-score matching was performed to match emergency to non-emergency patients 1:1. Our primary outcome was a composite of any complication. Our secondary endpoints were hospital readmission, unplanned reoperation and 30-day morbidity and mortality. RESULTS: In the unmatched analyses (n = 12,181/95.28% elective and n = 603/4.72% emergency) of Crohn's patients undergoing colectomy, 20% of elective and 42% of emergency patients experienced a complication (p < 0.001). Over 20 outcomes measured including length of stay (LOS), readmission, infections and respiratory, cardiovascular and renal complications, were worse in the emergency cohort. In the matched analyses (n = 400 emergency/400 elective patients) only the categories of any complication (OR 1.44, 1.06-1.96 95% CI, p = 0.02), any surgical site infection (SSI, OR 1.53, 1.07-2.19 95% CI, p = 0.02), superficial SSI (OR 2.25, 1.14-4.44 95% CI, p = 0.02), organ space SSI (1.58 OR 1.04-2.4 95% CI, p = 0.03), unplanned intubation (OR 5.0, 1.45-17.27 95% CI, p = 0.01), ventilation > 48 h (OR 9.0, 1.4-38.79 95% CI, p = 0.003) and septic shock (OR 4.5, 1.86-10.9 95% CI, p < 0.001) were higher in the emergency cohort. CONCLUSIONS: Matching CD patients resulted in a loss of the observed increase in cardiovascular and renal complications, reoperation and LOS following emergency surgery; however, SSIs and respiratory complications remained increased despite matching.

Structural Characterization of the D179N and D179Y Variants of KPC-2 ß-Lactamase: Ω-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.

Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) present a global clinical threat, as these ß-lactamases confer resistance to carbapenems and oxyimino-cephalosporins. Recent clinically identified KPC variants with substitutions at Ambler position D179, located in the Ω loop, are resistant to the ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam, but susceptible to meropenem-vaborbactam. To gain insights into ceftazidime-avibactam resistance conferred by D179N/Y variants of KPC-2, crystal structures of these variants were determined. The D179N KPC-2 structure revealed that the change of the carboxyl to an amide moiety at position 179 disrupted the salt bridge with R164 present in wild-type KPC-2. Additional interactions were disrupted in the Ω loop, causing a decrease in the melting temperature. Shifts originating from N179 were also transmitted toward the active site, including ∼1-Å shifts of the deacylation water and interacting residue N170. The structure of the D179Y KPC-2 ß-lactamase revealed more drastic changes, as this variant exhibited disorder of the Ω loop, with other flanking regions also being disordered. We postulate that the KPC-2 variants can accommodate ceftazidime because the Ω loop is displaced in D179Y or can be more readily displaced in D179N KPC-2. To understand why the ß-lactamase inhibitor vaborbactam is less affected by the D179 variants than avibactam, we determined the crystal structure of D179N KPC-2 in complex with vaborbactam, which revealed wild-type KPC-2-like vaborbactam-active site interactions. Overall, the structural results regarding KPC-2 D179 variants revealed various degrees of destabilization of the Ω loop that contribute to ceftazidime-avibactam resistance, possible substrate-assisted catalysis of ceftazidime, and meropenem and meropenem-vaborbactam susceptibility.

Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) devices are an important element of the management of cystic fibrosis, and of other respiratory diseases. Whereas there have been reports in the literature of contamination of airway clearance devices and their surfaces by microbial pathogens, there is little evidence available regarding such contamination and its contribution to respiratory infection. AIM: To establish whether pathogenic bacteria can contaminate PEP devices in the context of normal cleaning and maintenance practices. METHODS: Patients' home-use clearance devices were brought to a routine clinic appointment and collected for microbiology sampling and analysis. The patients were provided with replacement devices. Nineteen such devices were collected from 17 patients, reflecting use of multiple devices by some patients. Swabs were taken and cultured from each patient's used device, the patient's airway, as well as from new unopened and unused devices that acted as controls. RESULTS: Seven of 19 devices (37%) tested positive for presence of pathogenic bacteria. Device-cleaning methods varied among patients and non-sterilization methods were found to be ineffective at removing pathogens. Microbial species found on the devices did not correlate with those identified from airway swabs. CONCLUSION: This study demonstrates the presence of pathogens on positive expiratory pressure devices. The potential for transmission of these pathogens to the patient's airway and the risk of infection remains unclear and requires further study.

Hand-hygiene-related clinical trials reported between 2014 and 2020: a comprehensive systematic review.

BACKGROUND: There is general consensus that hand hygiene is the most effective way to prevent healthcare-associated infections. However, low rates of compliance amongst healthcare workers have been reported globally. The coronavirus disease 2019 pandemic has further emphasized the need for global improvement in hand hygiene compliance by healthcare workers. AIM: This comprehensive systematic review provides an up-to-date compilation of clinical trials, reported between 2014 and 2020, assessing hand hygiene interventions in order to inform healthcare leaders and practitioners regarding approaches to reduce healthcare-associated infections using hand hygiene. METHODS: CINAHL, Cochrane, EMbase, Medline, PubMed and Web of Science databases were searched for clinical trials published between March 2014 and December 2020 on the topic of hand hygiene compliance among healthcare workers. In total, 332 papers were identified from these searches, of which 57 studies met the inclusion criteria. FINDINGS: Forty-five of the 57 studies (79%) included in this review were conducted in Asia, Europe and the USA. The large majority of these clinical trials were conducted in acute care facilities, including hospital wards and intensive care facilities. Nurses represented the largest group of healthcare workers studied (44 studies, 77%), followed by physicians (41 studies, 72%). Thirty-six studies (63%) adopted the World Health Organization's multi-modal framework or a variation of this framework, and many of them recorded hand hygiene opportunities at each of the 'Five Moments'. However, recording of hand hygiene technique was not common. CONCLUSION: Both single intervention and multi-modal hand hygiene strategies can achieve modest-to-moderate improvements in hand hygiene compliance among healthcare workers.

Assessment of the Role of 1,3-ß-d-Glucan Testing for the Diagnosis of Invasive Fungal Infections in Adults.

Detection of 1,3-ß-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.

Ocular Neural Heterotopia in a Moroccan Uromastyx (Uromastyx acanthinurus nigriventris).

A juvenile female Moroccan uromastyx (Uromastyx acanthinurus nigriventris) that died unexpectedly was necropsied. Necropsy examination revealed minimal intracoelomic fat, small numbers of intestinal nematodes and intraocular masses within the vitreous chamber of both eyes. One of the intraocular masses was focally contiguous with the optic nerve and composed of neuroparenchyma with rare glial cells, consistent with a diagnosis of neural heterotopia. This condition is considered a neuroectodermal malformation, readily recognized in human medicine but rarely reported in animals. To the authors' knowledge, this is the first case of intraocular neural heterotopia reported in a reptile.

Pharmacokinetics and Dialytic Clearance of Isavuconazole During In Vitro and In Vivo Continuous Renal Replacement Therapy.

The pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated. In vivo, mean (± SD) plasma PK parameters of isavuconazole were: C max 4.00±1.45 mg/L, C min 1.76±0.76 mg/L, t ½ 48.36±29.78 h, Vss 288.78±182.11 L, CLss 4.85±3.79 L/h, and AUC 54.01±20.98 mg ⋅ h/L. Transmembrane clearance represented just 0.7% of the total isavuconazole clearance. These data suggest that isavuconazole is not readily removed by CRRT and no dose adjustments are necessary.

Surgical management of a giant hepatic cyst with suspicious radiological features.

Cysts in the liver have a wide variety of aetiologies. Important features of malignancy based on various imaging techniques must be considered prior to any intervention. Perioperative decision making in complex or difficult cysts is key to appropriate patient management. A 66-year-old woman was referred to the outpatient department with a one-year history of intermittent, sharp, right upper quadrant pain, radiating to her back. Computed tomography and magnetic resonance imaging showed a large cyst in the right and left lobes of the liver with portal inflow closely related. Features such as wall thickening suspicious for cystadenocarcinoma were present. An open resection was planned but, based on perioperative findings, the cyst had features making it unsafe to perform excision. De-roofing, carefully controlled drainage and assessment of the internal aspect of the cyst were performed, which revealed an extremely close relationship to portal inflow. This case describes the decision-making process when faced with complex indeterminate pathology of the liver and proximity of critical structures.

Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms.

OBJECTIVES: To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam. METHODS: The performances of the Etest (bioMérieux), 30/20 µg disc (Hardy diagnostics) and 10/4 µg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines. RESULTS: A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 µg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 µg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal. CONCLUSIONS: Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 µg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.

A meta-analysis of the efficacy of prophylactic alpha-blockade for the prevention of urinary retention following primary unilateral inguinal hernia repair.

BACKGROUND: Urinary retention following inguinal hernia surgery is common and is believed to be associated with adrenergic over-stimulation of the smooth muscle in the bladder neck and prostate. The efficacy of prophylactic alpha-blockade in the prevention of urinary retention following elective inguinal hernia repair in males is unknown. METHODS: A comprehensive literature search was performed adhering to PRISMA guidelines. Each study was reviewed and data were extracted. Random-effects models were used to combine data. RESULTS: Five randomized studies describing 456 patients were identified. General or spinal anaesthetic were used. Prophylactic alpha-blockade decreases the risk of urinary retention requiring catheterisation following elective unilateral inguinal hernia repair compared to control groups (OR:0.179, 95% CI:0.043-0.747, p:0.018). Rates of urinary retention between treatment and control groups are reduced by 20.6%. No serious complications relating to alpha blockade occurred. CONCLUSIONS: Prophylactic alpha-blockade reduces urinary retention following elective inguinal hernia surgery under general or spinal anaesthetic.

Cucurbit[6]uril-Promoted Click Chemistry for Protein Modification.

Azide-alkyne cycloaddition is a powerful reaction for the formation of bioconjugates. When catalyzed by Cu(I) or strain promotion, this cycloaddition is considered to be a "click" reaction with many applications in chemical biology and materials science. We report a new type of azide-alkyne click chemistry for the synthesis of protein conjugates using cucurbit[6]uril (CB6) supramolecular chemistry. CB6-promoted azide-alkyne cycloaddition has been previously used for the synthesis of rotaxanes but has not been applied to the development of complex bioconjugates. By developing new substrates for CB6 click that do not contain any cross-reactive functional groups and by optimizing reaction conditions, we converted CB6 click chemistry from a rotaxane synthesis tool into a useful bioconjugation technique. Using these new parameters, we synthesized a series of protein conjugates including protein-peptide, protein-DNA, protein-polymer, and protein-drug conjugates. We further demonstrated that CB6 click can be used in conjunction with strain-promoted azide-alkyne cycloaddition to generate distinct bioconjugates in protein mixtures. CB6 click is a promising new reaction for the development of protein conjugates and can be applied toward the synthesis of complex biomaterials for a wide range of applications.

Rotaxane probes for protease detection by 129Xe hyperCEST NMR.

We report a CB6 rotaxane for the 129Xe hyperCEST NMR detection of matrix metalloprotease 2 (MMP-2) activity. MMP-2 is overexpressed in cancer tissue, and hence is a cancer marker. A peptide containing an MMP-2 recognition sequence was incorporated into the rotaxane, synthesized via CB6-promoted click chemistry. Upon cleavage of the rotaxane by MMP-2, CB6 became accessible for 129Xe@CB6 interactions, leading to protease-responsive hyperCEST activation.

Cardiac Na Channels: Structure to Function.

Heart rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. Opening of the primary cardiac voltage-gated sodium (NaV1.5) channel initiates cellular depolarization and the propagation of an electrical action potential that promotes coordinated contraction of the heart. The regularity of these contractile waves is critically important since it drives the primary function of the heart: to act as a pump that delivers blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. Perturbations to NaV1.5 may alter the structure, and hence the function, of the ion channel and are associated downstream with a wide variety of cardiac conduction pathologies, such as arrhythmias.

(129)Xe NMR Relaxation-Based Macromolecular Sensing.

We report a (129)Xe NMR relaxation-based sensing approach that exploits changes in the bulk xenon relaxation rate induced by slowed tumbling of a cryptophane-based sensor upon target binding. The amplification afforded by detection of the bulk dissolved xenon allows sensitive detection of targets. The sensor comprises a xenon-binding cryptophane cage, a target interaction element, and a metal chelating agent. Xenon associated with the target-bound cryptophane cage is rapidly relaxed and then detected after exchange with the bulk. Here we show that large macromolecular targets increase the rotational correlation time of xenon, increasing its relaxation rate. Upon binding of a biotin-containing sensor to avidin at 1.5 µM concentration, the free xenon T2 is reduced by a factor of 4.