The Zavanelli manoeuvre revisited: A review of the literature and a guide to performing cephalic replacement for severe shoulder dystocia.

The Zavanelli manoeuvre is often the final resort of the clinician facing undeliverable shoulder dystocia and we present retrospective pooled data comprising 110 shoulder dystocia cases, 11 impacted breech and 11 locked twin deliveries assessed from ten case series and 38 individual case reports. Although recommended when other external and internal manipulations have failed, we suspect that many clinicians have not had formal training on how to conduct the manoeuvre and may be unfamiliar with the steps involved, leading to a reluctance and delay in initiating this. We describe original descriptions of the manoeuvre, examine its use in intractable shoulder dystocia and illustrate stepwise the cephalic replacement technique. For this review, we have concentrated mainly on the outcomes of the Zavanelli manoeuvre in shoulder dystocia but have also touched on its role in impacted breech and locked twin deliveries. Lastly, we discuss the cognitive load an obstetrician faces when having to make time critical decisions in severe shoulder dystocia and share how other disciplines train and prepare their personnel to manage similar rare and unexpected scenarios.

Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection.

A significant proportion of urinary tract infection (UTI) patients experience recurrent episodes, due to deep tissue infection and treatment-resistant bacterial reservoirs. Direct bladder instillation of antibiotics has proved disappointing in treating UTI, likely due to the failure of infused antibiotics to penetrate the bladder epithelium and accumulate to high enough levels to kill intracellular bacteria. This work investigates the use of nitrofurantoin loaded poly(lactic-co-glycolic acid) (PLGA) particles to improve delivery to intracellular targets for the treatment of chronic UTI. Using electrohydrodynamic atomisation, we produced particles with an average diameter of 2.8 µm. In broth culture experiments, the biodegradable particles were effective against a number of UTI-relevant bacterial strains. Dye-loaded particles demonstrated that intracellular delivery was achieved in all cells in 2D cultures of a human bladder epithelial progenitor cell line in a dose-dependent manner, achieving far higher efficiency and concentration than equivalent quantities of free drug. Time-lapse video microscopy confirmed that delivery occurred within 30 min of administration, to 100% of cells. Moreover, the particles were able to deliver the drug to cells through multiple layers of a 3D human bladder organoid model causing minimal cell toxicity, displaying superior killing of bacterial reservoirs harboured within bladder cells compared with unencapsulated drug. The particles were also able to kill bacterial biofilms more effectively than the free drug. These results illustrate the potential for using antibiotic-loaded microparticles to effectively treat chronic UTIs. Such a delivery method could be extrapolated to other clinical indications where robust intracellular delivery is required, such as oncology and gene therapy.

Cross-over data supporting long-term antibiotic treatment in patients with painful lower urinary tract symptoms, pyuria and negative urinalysis.

PURPOSE: To measure the effects of an unplanned, sudden cessation of treatment in an unselected group of patients with chronic painful LUTS managed with protracted antimicrobial treatment and to report these observational data collected from a cross-over process. MATERIALS AND METHODS: The imposition of a guideline resulted in the immediate cessation of antibiotic treatment in a cohort of patients with chronic painful LUTS and microscopic pyuria. Patients were assessed before treatment withdrawal, whilst off treatment, and following reinstatement. Outcome measures included a validated symptom score, microscopic enumeration of urinary white cells and uroepithelial cells, and routine urine culture. RESULTS: These patients had reported treatment-resistant, painful LUTS for a mean of 6.5 years before treatment at this centre. Treatment was stopped in 221 patients (female = 210; male = 11; mean age = 56 years; SD = 17.81). Sixty-six per cent of women were post-menopausal. After unplanned treatment cessation, 199 patients (90%; female = 188; male = 9) reported deterioration. Eleven patients required hospital care in association with disease recurrence, including acute urinary tract infection (UTI) and urosepsis. Symptom scores increased after cessation and recovered on reinitiating treatment (F = 33; df = 2; p < 0.001). Urinary leucocyte (F = 3.7; df = 2; p = 0.026) and urothelial cells counts mirrored symptomatic changes (F = 6.0; df = 2; p = 0.003). Routine urine culture results did not reflect changes in disease status. CONCLUSION: These data support the hypothesis that treating painful LUTS associated with pyuria with long-term antimicrobial courses, despite negative urine culture, is effective. The microscopy of fresh unspun, unstained urine to count white cells and epithelial cells offers a valid method of monitoring disease. An unplanned cessation of antibiotic therapy produced a resurgence of symptoms and lower urinary tract inflammation in patients with chronic LUTS, supporting an infective aetiology below the level of routine detection.

A urine-dependent human urothelial organoid offers a potential alternative to rodent models of infection.

Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers. The apical surface differentiated into enlarged and flattened umbrella-like cells bearing characteristic tight junctions, structures resembling asymmetric unit membrane plaques, and a glycosaminoglycan layer. The apical cells also expressed cytokeratin-20, a spatial feature of the mammalian urothelium. Urine itself was necessary for full development, and undifferentiated cells were urine-tolerant despite the lack of membrane plaques and a glycosaminoglycan layer. Infection with Enterococcus faecalis revealed the expected invasive outcome, including urothelial sloughing and the formation of intracellular colonies similar to those previously observed in patient cells. This new biomimetic model could help illuminate invasive behaviours of uropathogens, and serve as a reproducible test bed for disease formation, treatment and resolution in patients.

Two cases of abnormal liver function associated with H1N1 infection in pregnancy.

Two patients with recent H1N1 virus infection in pregnancy were found to have raised transaminases. They have both had a mild illness and have recovered with no adverse effects, and one has delivered a healthy baby while the other is still pregnant. We suggest that the deranged transaminase concentrations were directly linked to the viral infection in the first patient as the abnormal blood results predated treatment. The second case is less clear.

Proctectomy for rectal cancer in patients with prior spinal cord injury.

INTRODUCTION: Limited published information is available concerning the clinical course of spinal cord injured (SCI) patients who later develop rectal cancer and undergo proctectomy. We hypothesized that such patients would have poorer outcomes than comparable neurally-intact patients. METHODS: We conducted a retrospective study of all SCI veterans receiving care at all Department of Veterans Affairs (DVA) Medical Centers who subsequently underwent proctectomy for rectal cancer during fiscal years 1993-2002. Only patients with SCI due to trauma who met American Spinal Injury Association type A criteria (complete cord injury) were analyzed. The search strategy utilized DVA datasets plus data extracted from medical records. RESULTS: There were 33,758 patients with ICD-9-CM diagnosis codes for SCI and 5246 patients with ICD-9-CM procedure codes for proctectomy due to rectal cancer; 72 patients were in both datasets. We received records for 72 patients and excluded 67 after chart review. Incorrect coding (44) and incomplete spinal cord lesions (9) were the most common exclusion criteria. Five patients were considered evaluable. The mean age at diagnosis was 65 (range 49-80). All five had symptomatic cancers and two (40%) had major comorbidities at admission. Postoperative complications occurred in four (80%). The winsorized mean length of stay was 28 days. CONCLUSIONS: The complication rate and length of stay for SCI patients undergoing proctectomy for rectal cancer were higher than those reported for otherwise comparable neurally-intact patients. SCI should be considered a risk factor for adverse outcomes in operations for rectal cancer as in other major surgery.