Changes in antimicrobial resistance in acute otitis media and otitis externa.

OBJECTIVES: Acute otitis media (AOM) and otitis externa (OE) are common ear infections which may warrant antibiotic therapy. For many infections, there is a rise in antimicrobial resistance, which is associated with treatment failure, morbidity, prolonged hospitalisation and mortality. This study aimed to identify longitudinal changes in microbiology and antimicrobial resistance in aural swabs taken from patients with AOM or OE. DESIGN: Retrospective observational analysis. SETTING: Aural samples processed at Manchester Medical Microbiology Partnership Laboratories between January 2008 and December 2018 were analysed to record organism isolated and antimicrobial sensitivity. PARTICIPANTS: Individual aural swabs from 7200 patients. MAIN OUTCOME MEASURES: Changes in the incidence of organisms and antimicrobial resistance between two time periods (2008-2012 and 2013-2018) were compared using the chi-squared test (alpha = 0.05). RESULTS: From 7200 swabs, 2879 (40%) were from children. The most frequently isolated organisms were Staphylococcus aureus (25%), Pseudomonas aeruginosa (24.4%), yeast (9.1%), mixed anaerobes (7.9%) and Haemophilus influenzae (6.1%). In children aged 0-4 years, H. influenzae had particularly high incidence (25%). Overall, the incidence of P. aeruginosa decreased significantly with time (p = 0.05). Isolates displaying resistance to one or more antimicrobial agents increased significantly in number in the second time period for P. aeruginosa (p = 0.04) and H. influenzae (p = 0.03). There was increased resistance to amoxicillin for P. aeruginosa (p = 0.01) and to erythromycin for H. influenzae (p < 0.01). CONCLUSION: Variations in type and frequency of organisms with increasing age likely result from differences in the preponderance of AOM compared to OE in children versus adults. We found increasing antimicrobial resistance for two organisms commonly isolated from AOM and OE infections, suggesting that aspects of current UK treatment practices and national recommendations may need to be revised.

Intraoperative interventions for preventing surgical site infection: an overview of Cochrane Reviews.

BACKGROUND: Surgical site infection (SSI) rates vary from 1% to 5% in the month following surgery. Due to the large number of surgical procedures conducted annually, the costs of these SSIs can be considerable in financial and social terms. Many interventions are used with the aim of reducing the risk of SSI in people undergoing surgery. These interventions can be broadly delivered at three stages: preoperatively, intraoperatively and postoperatively. The intraoperative interventions are largely focused on decontamination of skin using soap and antiseptics; the use of barriers to prevent movement of micro-organisms into incisions; and optimising the patient's own bodily functions to promote best recovery. Both decontamination and barrier methods can be aimed at people undergoing surgery and operating staff. Other interventions focused on SSI prevention may be aimed at the surgical environment and include methods of theatre cleansing and approaches to managing theatre traffic. OBJECTIVES: To present an overview of Cochrane Reviews of the effectiveness and safety of interventions, delivered during the intraoperative period, aimed at preventing SSIs in all populations undergoing surgery in an operating theatre. METHODS: Published Cochrane systematic reviews reporting the effectiveness of interventions delivered during the intraoperative period in terms of SSI prevention were eligible for inclusion in this overview. We also identified Cochrane protocols and title registrations for future inclusion into the overview. We searched the Cochrane Library on 01 July 2017. Two review authors independently screened search results and undertook data extraction and 'Risk of bias' and certainty assessment. We used the ROBIS (risk of bias in systematic reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the certainty of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. MAIN RESULTS: We included 32 Cochrane Reviews in this overview: we judged 30 reviews as being at low risk of bias and two at unclear risk of bias. Thirteen reviews had not been updated in the past three years. Two reviews had no relevant data to extract. We extracted data from 30 reviews with 349 included trials, totaling 73,053 participants. Interventions assessed included gloving, use of disposable face masks, patient oxygenation protocols, use of skin antiseptics for hand washing and patient skin preparation, vaginal preparation, microbial sealants, methods of surgical incision, antibiotic prophylaxis and methods of skin closure. Overall, the GRADE certainty of evidence for outcomes was low or very low. Of the 77 comparisons providing evidence for the outcome of SSI, seven provided high- or moderate-certainty evidence, 39 provided low-certainty evidence and 31 very low-certainty evidence. Of the nine comparisons that provided evidence for the outcome of mortality, five provided low-certainty evidence and four very low-certainty evidence.There is high- or moderate-certainty evidence for the following outcomes for these intraoperative interventions. (1) Prophylactic intravenous antibiotics administered before caesarean incision reduce SSI risk compared with administration after cord clamping (10 trials, 5041 participants; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.81; high-certainty evidence - assessed by review authors). (2) Preoperative antibiotics reduce SSI risk compared with placebo after breast cancer surgery (6 trials, 1708 participants; RR 0.74, 95% CI 0.56 to 0.98; high-certainty evidence - assessed by overview authors). (3) Antibiotic prophylaxis probably reduce SSI risk in caesarean sections compared with no antibiotics (82 relevant trials, 14,407 participants; RR 0.40, 95% CI 0.35 to 0.46; moderate-certainty evidence; downgraded once for risk of bias - assessed by review authors). (4) Antibiotic prophylaxis probably reduces SSI risk for hernia repair compared with placebo or no treatment (17 trials, 7843 participants; RR 0.67, 95% CI 0.54 to 0.84; moderate-certainty evidence; downgraded once for risk of bias - assessed by overview authors); (5) There is currently no clear difference in the risk of SSI between iodine-impregnated adhesive drapes compared with no adhesive drapes (2 trials, 1113 participants; RR 1.03, 95% CI 0.66 to 1.60; moderate-certainty evidence; downgraded once for imprecision - assessed by review authors); (6) There is currently no clear difference in SSI risk between short-term compared with long-term duration antibiotics in colorectal surgery (7 trials; 1484 participants; RR 1.05 95% CI 0.78 to 1.40; moderate-certainty evidence; downgraded once for imprecision - assessed by overview authors). There was only one comparison showing negative effects associated with the intervention: adhesive drapes increase the risk of SSI compared with no drapes (5 trials; 3082 participants; RR 1.23, 95% CI 1.02 to 1.48; high-certainty evidence - rated by review authors). AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on use of intraoperative treatments for the prevention of SSIs from all currently published Cochrane Reviews. There is evidence that some interventions are useful in reducing SSI risk for people undergoing surgery, such as antibiotic prophylaxis for caesarean section and hernia repair, and also the timing of prophylactic intravenous antibiotics administered before caesarean incision. Also, there is evidence that adhesive drapes increase SSI risk. Evidence for the many other treatment choices is largely of low or very low certainty and no quality-of-life or cost-effectiveness data were reported. Future trials should elucidate the relative effects of some treatments. These studies should focus on increasing participant numbers, using robust methodology and being of sufficient duration to adequately assess SSI. Assessment of other outcomes such as mortality might also be investigated as part of non-experimental prospective follow-up of people with SSI of different severity, so the risk of death for different subgroups can be better understood.

Reliability of a Standardized Nasal Anatomic Worksheet and Correlation With Subjective Nasal Airway Obstruction.

IMPORTANCE: Nasal obstruction is a common chief concern; however, a comprehensive standardized worksheet for evaluating nasal obstruction has not been developed. OBJECTIVE: To evaluate the interrater reliability between staff surgeons and otolaryngology residents using a worksheet-based standardized nasal examination and to identify specific examination findings correlated with the Nasal Obstruction Symptom Evaluation quality-of-life score. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted from June to July 2012 involved 50 adults presenting to an otolaryngology clinic at a tertiary care hospital. The patients were examined by 2 board-certified facial plastic surgeons and 2 otolaryngology residents. EXPOSURES: The inferior turbinates, septum, and internal and external nasal valve narrowing and collapse were graded bilaterally from a scale of 0 to 3 with the aid of a standardized nasal anatomy worksheet. The findings were compared between the attending staff, residents, and the entire group. MAIN OUTCOMES AND MEASURES: The Cohen κ coefficient for interrater reliability was calculated for each of the graded metrics. The Nasal Obstruction Symptom Evaluation scores were correlated with anatomic scores. RESULTS: Of the 49 patients included in the final analysis, the mean age was 43.6 years (range, 21-82 years), and 31 were male (66.3%). Among all attending and resident examiners, a moderate to fair, statistically significant interrater reliability coefficient (P < .001) was observed in the following nasal anatomic measurements: left and right Cottle (κ = 0.582 [95% CI, 0.463-0.700] and κ = 0.580 [95% CI, 0.461-0.698], respectively), modified Cottle (κ = 0.491 [95% CI, 0.373-0.609] and κ = 0.560 [95% CI, 0.442-0.679], respectively), dynamic internal nasal valve collapse (κ = 0.204 [95% CI, 0.118-0.290] and κ = 0.232 [95% CI, 0.140-0.323], respectively), and inferior turbinate hypertrophy (κ = 0.252 [95% CI, 0.152-0.352] and κ = 0.235 [95% CI, 0.153-0.317], respectively). The trend of examination interrater reliability was similar for attending staff and the otolaryngology residents. The Nasal Obstruction Symptom Evaluation score correlated with the mean total anatomic worksheet score (Spearman ρ = 0.301; P = .048). CONCLUSIONS AND RELEVANCE: Interrater reliability is high in both residents and attending staff for dynamic nasal airway examinations evaluating the internal and external nasal valves and for turbinate hypertrophy assessment. The total nasal anatomic score using a standardized worksheet correlates to patient-reported nasal-specific quality of life. LEVEL OF EVIDENCE: NA.

Cecal obstruction caused by paratubal cysts in a 24-year-old woman.

A 24-year-old woman with no significant past medical or surgical history presented with diffuse abdominal pain and distention with decreased frequency of bowel movements for 1 month. A computerized tomography scan showed a massively dilated cecum suggesting obstruction. Exploratory laparotomy revealed bowel obstruction secondary to a band of fibroadipose tissue associated with paratubal cysts originating from the left fallopian tube. Removal of the band was performed with thorough examination of the bowel confirming absence of perforation or necrosis.

Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.

BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor SPINK1 further increase the risk of pancreatitis in these patients. METHODS: We screened patients and controls for variants in SPINK1 associated with risk of chronic pancreatitis and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, 150 unrelated controls, 375 additional controls for limited genotyping. CFTR wild-type and p.R75Q were cloned and expressed in HEK293 cells, and relative conductances of HCO(3)(-) and Cl(-) were measured. RESULTS: SPINK1 variants were identified in 36% of subjects and 3% of controls (odds ratio [OR], 18.1). One variant of CFTR not associated with CF, p.R75Q, was found in 16% of subjects and 5.3% of controls (OR, 3.4). Coinheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.38% of controls (OR, 25.1). Patch-clamp recordings of cells that expressed CFTR p.R75Q showed normal chloride currents but significantly reduced bicarbonate currents (P = .0001). CONCLUSIONS: The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk of pancreatitis. Coinheritance of p.R75Q or CF causing CFTR variants with SPINK1 variants significantly increases the risk of ICP.

Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism.

BACKGROUND: Pancreatic cancer is a deadly disease. Discovery of the mutated genes that cause the inherited form(s) of the disease may shed light on the mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for familial pancreatic cancer to chromosome location 4q32-34. In this study, our goal was to discover the identity of the familial pancreatic cancer gene on 4q32 and determine the function of that gene. METHODS AND FINDINGS: A customized microarray of the candidate chromosomal region affecting pancreatic cancer susceptibility revealed the greatest expression change in palladin (PALLD), a gene that encodes a component of the cytoskeleton that controls cell shape and motility. A mutation causing a proline (hydrophobic) to serine (hydrophilic) amino acid change (P239S) in a highly conserved region tracked with all affected family members and was absent in the non-affected members. The mutational change is not a known single nucleotide polymorphism. Palladin RNA, measured by quantitative RT-PCR, was overexpressed in the tissues from precancerous dysplasia and pancreatic adenocarcinoma in both familial and sporadic disease. Transfection of wild-type and P239S mutant palladin gene constructs into HeLa cells revealed a clear phenotypic effect: cells expressing P239S palladin exhibited cytoskeletal changes, abnormal actin bundle assembly, and an increased ability to migrate. CONCLUSIONS: These observations suggest that the presence of an abnormal palladin gene in familial pancreatic cancer and the overexpression of palladin protein in sporadic pancreatic cancer cause cytoskeletal changes in pancreatic cancer and may be responsible for or contribute to the tumor's strong invasive and migratory abilities.

A New Microarray, Enriched in Pancreas and Pancreatic Cancer cDNAs to Identify Genes Relevant to Pancreatic Cancer.

BACKGROUND: Identification and characterization of genes that are relevant to pancreatic cancer remains a priority for developing detection and diagnostic tests and identifying targets for treatment. MATERIALS AND METHODS: In order to discover relevant genes, we developed a microarray composed of 5763 pancreas and pancreatic cancer cDNA clones, representing genes of known and unknown function. The Pittsburgh Pancreas Enriched ARray (PittPEAR) was used to compare the gene expression differences between pancreatic cancer and normal pancreas. RESULTS: Two hundred and sixty-four genes were identified: 85 were overexpressed and 176 were underexpressed in cancer compared to normal tissue. Two of the top five genes included the cell cycle division 37 (CDC37) and period Drosophila homolog protein 1 (PER1), which play critical roles in cell division and transcriptional regulation, respectively. Underexpression of many genes probably reflected the loss of acinar and islet cells from the tumors. The biological functions of overexpressed genes include immune response genes, cytoskeletal and genes related to the extracellular matrix, cell invasion, migration, adhesion and motility. Apoptosis and transcription factor genes were also identified. CONCLUSION: We conclude that the PittPEAR microarray provides a useful tool for identifying genes that are relevant to the development and maintenance of pancreatic cancer.