A review of inpatient urology consultations in an Irish tertiary referral centre

IntroductionOur institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period.MethodsAll consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters.ResultsSeven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15–96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting.ConclusionsInpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.     

Surgical management of symptomatic Chiari II malformation in infants and children

Purpose

Variation exists in the surgical methods employed for decompression of Chiari II malformation (CIIM), yet an evaluation of these techniques has not been performed. The purpose of this study was to assess the efficacy of bony decompression (cervical laminectomy alone versus suboccipital craniectomy with laminectomy) with or without dural augmentation for the treatment of symptomatic CIIM.

Methods

Clinical records of children 0–18 years of age who underwent surgical repair of myelomeningocele or CIIM decompression at St. Louis Children’s Hospital (SLCH) from 1990–2011 were reviewed. Signs/symptoms prompting decompression, surgical technique, operative parameters, and clinical outcomes were recorded for analysis.

Results

Thirty-three subjects were treated at SLCH for CIIM decompression. Twenty-six subjects underwent bony decompression only (21 cervical laminectomy alone, 5 suboccipital craniectomy?+?cervical laminectomy) while seven underwent bony decompression with upfront dural augmentation (three cervical laminectomy alone, four suboccipital craniectomy?+?cervical laminectomy). Median follow up was 5.0 years (range, 3 months–19 years). Symptomatic improvement was noted in 20/33 subjects (60.6 %). Sixty-two (61.5 %) percent of children who underwent bony decompression had symptomatic improvement, compared with 57.1 % of those with upfront dural augmentation (p?=?0.37). Estimated blood loss, operative time, and length of perioperative hospital stay appeared lower in the bony decompression group but were not statistically different in this limited cohort.

Conclusions

The results from this series suggest that bony CIIM decompression via tailored cervical laminectomies alone, without suboccipital craniectomy or upfront dural augmentation, is a reasonable initial management approach for decompression of symptomatic CIIM.     

Listeria meningitis complicating a patient with ulcerative colitis on concomitant infliximab and hydrocortisone

Infliximab, a monoclonal antibody directed against tumour necrosis factor, is an effective therapy for moderate-to-severe ulcerative colitis and Crohn’s disease. Uncommonly, serious opportunistic infections have occurred in patients after infliximab administration. Here, we describe meningitis caused by Listeria monocytogenes developing in a 37-year-old man with ulcerative colitis refractory to intravenous corticosteroids 10 days after receiving his first infusion of infliximab. With the increasing use of tumour necrosis factor-α-neutralizing agents, clinicians should be aware of the risk of opportunistic infections caused by L. monocytogenes in patients with inflammatory bowel disease following infliximab treatment. The half-life of infliximab is 9.5 days; therefore, patients tend to be more susceptible in the immediate period following infusion. Patients receiving anti-TNF therapy should be advised to avoid foods such as soft cheeses and unpasteurized dairy products.     

Nonredundant roles of antibody,cytokines, and perforin in the eradication of established Her-2/neu carcinomas

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential.     

Brief review: Neuraxial analgesia in refractory malignant pain

Purpose

This narrative review aims to inform health care practitioners of the current literature surrounding the use of intrathecal (IT) and epidural analgesia in cancer patients with refractory pain at end of life. Topics discussed and reviewed include: patient selection, treatment planning, procedure, equipment, medications, complications, policies and procedures, as well as directions for future research.

Principal findings

Cancer pain is inadequately treated in an estimated 10% of patients with malignant pain despite the implementation of the World Health Organization three-step analgesic ladder. This has prompted some to advocate for the addition of a fourth step that would include neuraxial interventions. There is moderate evidence supporting the safety and efficacy of IT drug therapy in cancer patients with refractory pain. A detailed assessment and interdisciplinary team approach is necessary to develop and implement care plans for patients requiring neuraxial analgesia. Neuraxial analgesia can significantly improve pain and reduce side effects, but this must be balanced against the increased complexity of care and the risk of uncommon but serious complications.

Conclusion

Neuraxial drug delivery gives clinicians more options to manage refractory pain at end of life and should be offered to patients with intractable cancer pain. Teams should be interprofessional with clear delineation of roles and responsibilities. They should discuss advanced discharge planning with the patient prior to implantation as well as provide on-call support.     

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual''s susceptibility to depression.     

Altered peptide ligands induce quantitatively but not qualitatively different intracellular signals in primary thymocytes

Interaction of the T cell receptor (TCR) with peptide/major histocompatibility complexes (MHC) in the thymus is of critical importance for developing thymocytes. In a previous study, we described an antagonist peptide that inhibited negative selection of transgenic thymocytes induced by an agonist peptide. In this study we show that this antagonist peptide can induce positive selection of CD8⁺ thymocytes more efficiently than the agonist or the weak agonist peptides, whereas the opposite is true for their ability to cause negative selection. The intracellular signals induced in thymocytes by such peptides after TCR ligation was examined in CD4⁺8⁺ double-positive thymocytes from F5/β₂m^o/Rag-1^o transgenic mice. TCR ligation with either the agonist, weak agonist, or antagonist peptide variants resulted in hyperphosphorylation of CD3ζ, CD3, ZAP-70, Syk, Vav, SLP-76, and pp36–38. The extent of phosphorylation of these intracellular proteins correlated with the efficiency with which the peptide analogs induced apoptosis of immature thymocytes. Unexpectedly, there was no correlation between the upstream TCR signaling pathways analyzed and the capacity of the different peptides to induce positive selection.