Recurrence of biliary disease following non-operative management in elderly patients.

INTRODUCTION: The purpose of this study was to determine the proportion of symptomatic recurrence following initial non-operative management of gallstone disease in the elderly and to test possible predictors. METHODS: This is a single institution retrospective chart review of patients 65 years and older with an initial hospital visit (V1) for symptomatic gallstone disease, over a 4-year period. Patients with initial "non-operative" management were defined as those without surgery at V1 and without elective surgery at visit 2 (V2). Baseline characteristics included age, sex, Charlson comorbidity index (CCI), diagnosis, and interventions (ERCP or cholecystostomy) at V1. Outcomes assessed over 1 year were as follows: recurrence (any ER/admission visit following V1), surgery, complications, and mortality. A survival analysis using a Cox proportional hazards model was performed to assess predictors of recurrence. RESULTS: There were 195 patients initially treated non-operatively at V1. Mean age was 78.3 ± 7.8 years, 45.6% were male, and the mean CCI was 2.1 ± 1.9. At V1, 54.4% had a diagnosis of biliary colic or cholecystitis, while 45.6% had a diagnosis of cholangitis, pancreatitis, or choledocholithiasis. 39.5% underwent ERCP or cholecystostomy. Excluding 10 patients who died at V1, 31.3% of patients had a recurrence over the study period. Among these, 43.5% had emergency surgery, 34.8% had complications, and 4.3% died. Median time to first recurrence was 2 months (range 6 days-4.8 months). Intervention at V1 was associated with a lower probability of recurrence (HR 0.3, CI [0.14-0.65]). CONCLUSION: One-third of elderly patients will develop a recurrence following non-operative management of symptomatic biliary disease. These recurrences are associated with significant rates of emergency surgery and morbidity. Percutaneous or endoscopic therapies may decrease the risk of recurrence.

Gallstone disease in the elderly: are older patients managed differently?

BACKGROUND: This study aimed to describe the differences in the management of symptomatic gallstone disease within different elderly groups and to evaluate the association between older age and surgical treatment. METHODS: This single-institution retrospective chart review included all patients 65 years old and older with an initial hospital visit for symptomatic gallstone disease between 2004 and 2008. The patients were stratified into three age groups: group 1 (age, 65-74 years), group 2 (age, 75-84 years), and group 3 (age, ≥ 85 years). Patient characteristics and presentation at the initial hospital visit were described as well as the surgical and other nonoperative interventions occurring over a 1-year follow-up period. Logistic regression was performed to assess the effect of age on surgery. RESULTS: Data from 397 patient charts were assessed: 182 in group 1, 160 in group 2, and 55 in group 3. Cholecystitis was the most common diagnosis in groups 1 and 2, whereas cholangitis was the most common diagnosis in group 3. Elective admissions to a surgical ward were most common in group 1, whereas urgent admissions to a medical ward were most common in group 3. Elective surgery was performed at the first visit for 50.6% of group 1, for 25.6% of group 2, and for 12.7% of group 3, with a 1-year cumulative incidence of surgery of 87.4% in group 1, 63.5% in group 2, and 22.1% in group 3. Inversely, cholecystostomy and endoscopic retrograde cholangiopancreatography (ERCP) were used more often in the older groups. Increased age (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.84-0.91) and the Charlson Comorbidity Index (OR, 0.80; 95% CI, 0.69-0.94) were significantly associated with a decreased probability of undergoing surgery within 1 year after the initial visit. CONCLUSION: Even in the elderly population, older patients presented more frequently with severe disease and underwent more conservative treatment strategies. Older age was independently associated with a lower likelihood of surgery.

Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation.

Delayed wound healing can cause significant issues for immobile and ageing individuals as well as those living with co-morbid conditions such as diabetes, cardiovascular disease, and cancer. These delays increase a patient's risk for infection and, in severe cases, can result in the formation of chronic, non-healing ulcers (e.g., diabetic foot ulcers, surgical site infections, pressure ulcers and venous leg ulcers). Chronic wounds are very difficult and expensive to treat and there is an urgent need to develop more effective therapeutics that restore healing processes. Sustained innate immune activation and inflammation are common features observed across most chronic wound types. However, the factors driving this activation remain incompletely understood. Emerging evidence suggests that the composition and structure of the wound microbiome may play a central role in driving this dysregulated activation but the cellular and molecular mechanisms underlying these processes require further investigation. In this review, we will discuss the current literature on: 1) how bacterial populations and biofilms contribute to chronic wound formation, 2) the role of bacteria and biofilms in driving dysfunctional innate immune responses in chronic wounds, and 3) therapeutics currently available (or underdevelopment) that target bacteria-innate immune interactions to improve healing. We will also discuss potential issues in studying the complexity of immune-biofilm interactions in chronic wounds and explore future areas of investigation for the field.

Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis.

Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290rd16 mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290rd16 allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290rd16 and Mkksko alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies.

IQCB1 mutations in patients with leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) is genetically heterogeneous, with 15 genes identified thus far, accounting for ∼70% of LCA patients. The aim of the present study was to identify new genetic causes of LCA. METHODS: Homozygosity mapping in >150 LCA patients of worldwide origin was performed with high-density SNP microarrays to identify new disease-causing genes. RESULTS: In three isolated LCA patients, the authors identified large homozygous regions on chromosome 3 encompassing the IQCB1 gene, which has been associated with Senior-Loken syndrome (SLSN), characterized by nephronophthisis and retinal degeneration. Mutation analysis of IQCB1 in these three patients and a subsequent cohort of 222 additional LCA patients identified frameshift and nonsense mutations in 11 patients diagnosed with LCA. On re-inspection of the patient's disease status, seven were found to have developed SLSN, but four maintained the diagnosis of LCA as the kidney function remained normal. CONCLUSIONS: Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in LCA patients without nephronophthisis, rendering IQCB1 a new gene for LCA. However, these patients are at high risk for developing renal failure, which in early stages is often not recognized and can cause sudden death from fluid and electrolyte imbalance. It is therefore recommended that all LCA patients be screened for IQCB1 mutations, to follow them more closely for kidney disease.