Improving Intravenous and Subcutaneous Insulin Overlap During Treatment of Diabetic Ketoacidosis: A Quality Improvement Project.

Objective: To reduce the frequency of insufficient overlap of intravenous (IV) and subcutaneous (SC) insulin during the treatment of diabetic ketoacidosis (DKA) as a quality improvement project. Patients and Methods: Rates of insufficient IV and SC insulin overlap (< 2-hour overlap, SC insulin given after IV insulin discontinuation, or no SC insulin given after IV insulin discontinuation) were assessed in adults with DKA treated with IV insulin at a large tertiary care referral center in Rochester, Minnesota, from July 1, 2021, to March 15, 2023. After a preintervention analysis period, an electronic medical record-based best practice advisory was introduced to notify hospital providers discontinuing IV insulin if SC long-acting insulin had not been given in the previous 2-6 hours. Demographic characteristics and clinical outcomes before and after intervention were compared. Results: A total of 352 patient encounters were included (251 in the preintervention phase and 101 in the postintervention phase). The rate of insufficient IV to SC insulin overlap decreased from (88 of 251) 35.1% before intervention to (20 of 101) 19.8% after intervention (P=.005). The rate of posttransition hypoglycemia (<70 mg/dL; to convert to mmol/L, multiply by 0.0259) decreased from (27 of 251) 10.7% to (4 of 101) 4% after intervention (P=.04). Rates of posttransition hyperglycemia (>250 mg/dL), rebound DKA, length of hospital stay, and duration of IV insulin therapy were similar before and after intervention. Conclusion: Using quality improvement methodology, the rates of insufficient IV to SC insulin overlap during treatment of DKA in a large tertiary care referral center were measured and reduced through an electronic medical record-based best practice advisory targeting hospital providers.

Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans.

BACKGROUNDProglucagon can be processed to glucagon-like peptide1 (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this is affected by type 2 diabetes.METHODSWe therefore studied individuals with and without type 2 diabetes on two occasions in random order. On one occasion, exendin 9-39, a competitive antagonist of the GLP-1 Receptor (GLP1R), was infused, while on the other, saline was infused. The tracer dilution technique ([3-3H] glucose) was used to measure glucose turnover during fasting and during a hyperglycemic clamp.RESULTSExendin 9-39 increased fasting glucose concentrations; fasting islet hormone concentrations were unchanged, but inappropriate for the higher fasting glucose observed. In people with type 2 diabetes, fasting glucagon concentrations were markedly elevated and persisted despite hyperglycemia. This impaired suppression of endogenous glucose production by hyperglycemia.CONCLUSIONThese data show that GLP1R blockade impairs islet function, implying that intra-islet GLP1R activation alters islet responses to glucose and does so to a greater degree in people with type 2 diabetes.TRIAL REGISTRATIONThis study was registered at ClinicalTrials.gov NCT04466618.FUNDINGThe study was primarily funded by NIH NIDDK DK126206. AV is supported by DK78646, DK116231 and DK126206. CDM was supported by MIUR (Italian Minister for Education) under the initiative "Departments of Excellence" (Law 232/2016).

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of ß-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased ß-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and ß-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall ß-cell function quantified by the Disposition Index was unchanged, the dynamic component of ß-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of ß-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on ß-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the ß-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the ß-cell.

The Effect of Glucagon-Like Peptide 1 Receptor Blockade on Glucagon-Induced Stimulation of Insulin Secretion.

Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on ß-cells. However, its net contribution to physiologic insulin secretion in humans is unknown. To address this question, we studied individuals without diabetes in two separate experiments. Each subject was studied on two occasions in random order. In the first experiment, during a hyperglycemic clamp, glucagon was infused at 0.4 ng/kg/min, increasing by 0.2 ng/kg/min every hour for 5 h. On one day, exendin-9,39 (300 pmol/kg/min) was infused to block GLP-1R, while on the other, saline was infused. The insulin secretion rate (ISR) was calculated by nonparametric deconvolution from plasma concentrations of C-peptide. Endogenous glucose production and glucose disappearance were measured using the tracer-dilution technique. Glucagon concentrations, by design, did not differ between study days. Integrated ISR was lower during exendin-9,39 infusion (213 ± 26 vs. 191 ± 22 nmol/5 h, saline vs. exendin-9,39, respectively; P = 0.02). In the separate experiment, exendin-9,39 infusion, compared with saline infusion, also decreased the ß-cell secretory response to a 1-mg glucagon bolus. These data show that, in humans without diabetes, glucagon partially stimulates the ß-cell through GLP-1R.

COVID-19 Management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases Centre: A Retrospective Analysis.

Recent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is limited granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on management and outcome. We performed a retrospective single-centre analysis of clinical management and 28-day outcomes of consecutive adult inpatients with SARS-CoV-2 PCR-confirmed COVID-19 from 31 January to 16 April 2020 inclusive. In total, 316 cases were identified. Most patients were elderly (median age 75) with multiple comorbidities. One quarter were admitted from residential or nursing care. Mortality was 84 out of 316 (26.6%). Most deaths occurred in patients in whom a ceiling of inpatient treatment had been determined and for whom end of life care and specialist palliative care input was provided where appropriate. No deaths occurred in patients aged under 56 years. Decisions to initiate respiratory support were individualised after consideration of patient wishes, premorbid frailty and comorbidities. In total, 59 (18%) patients were admitted to intensive care, of which 31 (10% overall cohort) required intubation. Multiple logistic regression identified associations between death and age, frailty, and disease severity, with age as the most significant factor (odds ratio 1.07 [95% CI 1.03-1.10] per year increase, p < 0.001). These findings provide important clinical context to outcome data. Mortality was associated with increasing age. Most deaths were anticipated and occurred in patients with advance decisions on ceilings of treatment.

15-Year Experience with Multimodality Therapy Including Esophagectomy for Elderly Patients with Locoregional Esophageal Cancer.

BACKGROUND: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population. STUDY DESIGN: Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger." RESULTS: One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS). CONCLUSIONS: Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients.

Modeling Mixed Vascular and Alzheimer's Dementia Using Focal Subcortical Ischemic Stroke in Human ApoE4-TR:5XFAD Transgenic Mice.

Subcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer's disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We designed a novel mouse model of subcortical white matter ischemic stroke and AD that can inform our understanding of the cellular and molecular mechanisms of mixed vascular and AD dementia. Subcortical white matter ischemic stroke underlying forelimb motor cortex was induced by local stereotactic injection of an irreversible eNOS inhibitor. Subcortical white matter ischemic stroke or sham procedures were performed on human ApoE4-targeted-replacement (TR):5XFAD mice at 8 weeks of age. Behavioral tests were done at 7, 10, 15, and 20 weeks. A subset of animals underwent 18FDG-PET/CT. At 20 weeks of age, brain tissue was examined for amyloid plaque accumulation and cellular changes. Compared with sham E4-TR:5XFAD mice, those with an early subcortical ischemic stroke showed a significant reduction in amyloid plaque burden in the region of cortex overlying the subcortical stroke. Cognitive performance was improved in E4-TR:5XFAD mice with stroke compared with sham E4-TR:5XFAD animals. Iba-1+ microglial cells in the region of cortex overlying the subcortical stroke were increased in number and morphologic complexity compared with sham E4-TR:5XFAD mice, suggesting that amyloid clearance may be promoted by an interaction between activated microglia and cortical neurons in response to subcortical stroke. This novel approach to modeling mixed vascular and AD dementia provides a valuable tool for dissecting the molecular interactions between these two common pathologies.

Pediatric tracheostomy: A large single-center experience.

OBJECTIVES: To describe the epidemiology, specifically the indications, complications, and outcomes, of pediatric tracheostomies performed in one tertiary referral unit. METHODS: Single-center retrospective cohort study of pediatric patients undergoing tracheostomy between May 2010 and May 2018 at the Newcastle upon Tyne Hospitals, United Kingdom. RESULTS: One hundred seventy-two pediatric tracheostomies were performed during the study period with a median age of 141 (interquartile range [IQR] 51-484) days. The most common primary indication was long-term ventilation (38.4%, 66 of 172), followed by weaning from ventilation in cardiac patients (22.1%, 38 of 172). Only 5.2% (9 of 172) of our cohort underwent tracheostomy for subglottic stenosis. The vast majority of tracheostomies were performed electively, with just 6.4% (11 of 172) performed as an emergency procedure. Early and late complication rates were 9.8% (15 of 153) and 40.0% (61 of 153), respectively. Tracheostomy decannulation was successful in 44.4% of children (68 of 153). The median duration the tracheostomy was in situ was 397 (IQR 106-708) days. All-cause mortality was 22.1% (38 of 172), with tracheostomy-related mortality at 1.2% (2 of 172). CONCLUSION: We report one of the largest contemporary case series of pediatric tracheostomies. Present-day pediatric tracheostomy is primarily performed as an elective procedure in ventilated children under the age of 1 year. Pediatric tracheostomy should be considered as a long-term intervention in many children. Nevertheless, a large proportion of children are ultimately decannulated. It is important to acknowledge the significant morbidity associated with this intervention and the small-but-present risk of tracheostomy-related mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E375-E380, 2020.

Preclinical Evaluation of [18F]LCATD as a PET Tracer to Study Drug-Drug Interactions Caused by Inhibition of Hepatic Transporters.

The bile acid analogue [18F]LCATD (LithoCholic Acid Triazole Derivative) is transported in vitro by hepatic uptake transporters such as OATP1B1 and NTCP and efflux transporter BSEP. In this in vivo "proof of principle" study, we tested if [18F]LCATD may be used to evaluate drug-drug interactions (DDIs) caused by inhibition of liver transporters. Hepatic clearance of [18F]LCATD in rats was significantly modified upon coadministration of rifamycin SV or sodium fusidate, which are known to inhibit clinically relevant uptake transporters (OATP1B1, NTCP) and canalicular hepatic transporters (BSEP) in humans. Treatment with rifamycin SV (total dose 62.5 mg·Kg-1) reduced the maximum radioactivity of [18F]LCATD recorded in the liver from 14.2 ± 0.8% to 10.2 ± 0.9% and delayed t_max by 90 seconds relative to control rats. AUCliver 0-5 min, AUCbile 0-10 min and hepatic uptake clearance CLuptake,in vivo of rifamycin SV treated rats were significantly reduced, whereas AUCliver 0-30 min was higher than in control rats. Administration of sodium fusidate (30 mg·Kg-1) inhibited the liver uptake of [18F]LCATD, although to a lesser extent, reducing the maximum radioactivity in the liver to 11.5 ± 0.3%. These preliminary results indicate that [18F]LCATD may be a good candidate for future applications as an investigational tracer to evaluate altered hepatobiliary excretion as a result of drug-induced inhibition of hepatic transporters.

Gated metabolic myocardial imaging, a surrogate for dual perfusion-metabolism imaging by positron emission tomography.

OBJECTIVE: Perfusion-metabolism mismatch pattern on positron emission tomography (PET) predicts hibernating myocardium. We assess the ECG-gated metabolic PET as a surrogate for the perfusion-metabolism mismatch pattern on PET imaging. METHODS: 13N-Ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) are respectively perfusion and metabolism PET tracers. We used ECG gating to acquire FDG-PET to collect wall thickening (mechanical) data. These allow detection of metabolic activity in regions with reduced contraction (metabolism-mechanical mismatch pattern). We had two data sets on each patient: perfusion-metabolism and metabolism-mechanical data sets. We tested the hypothesis that metabolism-mechanical pattern on PET could predict perfusion-metabolism mismatch pattern. RESULTS: We studied 55 patients (48 males), mean age 62 years. All were in sinus rhythm, and had impaired left ventricular contraction. Perfusion-metabolism mismatch pattern was found in 26 patients. Metabolism-mechanical mismatch pattern was found in 25 patients. The results were concordant in 52 patients (95%). As a surrogate for perfusion-metabolism mismatch pattern, demonstration of metabolism-mechanical mismatch pattern is highly sensitive (92%) and specific (97%). In this cohort, the positive and negative predictive accuracy of the new method are 96% and 93%, respectively. CONCLUSION: Metabolism-mechanical mismatch pattern could predict perfusion-metabolism mismatch pattern in patients with myocardial viability criteria on PET. Prospective validation against the gold standard of improved myocardial contraction after revascularisation is needed.

Characterization of viability, scarring and hibernation of the myocardium supplied by epicardial coronary arteries with low flow grades.

OBJECTIVE: The aim of this study was to analyse the relationship between reduced coronary artery flow and myocardial viability, scarring and hibernation. PATIENTS AND METHODS: Coronary flow grades and collateral vessels were scored using the thrombolysis in myocardial infarction trial (TIMI) and the Rentrop and Cohen scoring systems, respectively. N-ammonia and fluorine-18-fluorodeoxyglucose (F-FDG) are the perfusion and metabolic markers on PET, respectively. The left ventricle was divided into three coronary territories. The area with the highest N-ammonia uptake was considered the reference region. Myocardial regions with F-FDG uptake of at least 50% of the reference region were considered viable and those with F-FDG uptake less than 50% of the reference region were considered scarred. Hibernation was considered present if the viable myocardium had significant wall motion abnormality. RESULTS: There were 80 (71 males) patients with 240 myocardial territories. TIMI 2-3 arteries supplied 151 regions (group A), and 89 regions were supplied by TIMI 0-1 arteries (group B). Viable myocardium was present in 140 (93%) regions of group A and in 76 (85%) regions of group B (P=0.068). Scarring was present in 40 (26%) regions in group A and in 49 (55%) regions in group B (P<0.0001). Wall motion data were available in 215 regions: 133 regions in group A and 82 regions in group B. Hibernating myocardium was predicted in 36 (28%) regions in group A and in 34 (41%) regions in group B (P<0.05). CONCLUSION: Myocardial regions supplied by arteries with TIMI 0-1 are characterized by significantly increased incidence of hibernation and scarring. Video abstract: http://links.lww.com/NMC/A115.

Neprilysin Is Required for Angiotensin-(1-7)'s Ability to Enhance Insulin Secretion via Its Proteolytic Activity to Generate Angiotensin-(1-2).

Recent work has renewed interest in therapies targeting the renin-angiotensin system (RAS) to improve ß-cell function in type 2 diabetes. Studies show that generation of angiotensin-(1-7) by ACE2 and its binding to the Mas receptor (MasR) improves glucose homeostasis, partly by enhancing glucose-stimulated insulin secretion (GSIS). Thus, islet ACE2 upregulation is viewed as a desirable therapeutic goal. Here, we show that, although endogenous islet ACE2 expression is sparse, its inhibition abrogates angiotensin-(1-7)-mediated GSIS. However, a more widely expressed islet peptidase, neprilysin, degrades angiotensin-(1-7) into several peptides. In neprilysin-deficient mouse islets, angiotensin-(1-7) and neprilysin-derived degradation products angiotensin-(1-4), angiotensin-(5-7), and angiotensin-(3-4) failed to enhance GSIS. Conversely, angiotensin-(1-2) enhanced GSIS in both neprilysin-deficient and wild-type islets. Rather than mediating this effect via activation of the G-protein-coupled receptor (GPCR) MasR, angiotensin-(1-2) was found to signal via another GPCR, namely GPCR family C group 6 member A (GPRC6A). In conclusion, in islets, intact angiotensin-(1-7) is not the primary mediator of beneficial effects ascribed to the ACE2/angiotensin-(1-7)/MasR axis. Our findings warrant caution for the concurrent use of angiotensin-(1-7) compounds and neprilysin inhibitors as therapies for diabetes.

Laparoscopic ultrasound for the diagnosis of choledocholithiasis: quick, safe, and effective.

Visualization of the common bile duct during laparoscopic cholecystectomy is frequently required to confirm or exclude choledocholithiasis. Although on-table cholangiogram (OTC) is the traditional imaging technique, laparoscopic ultrasound (LUS) is increasingly deployed for this purpose. We are reporting a 31-month experience with an LUS, starting from the initial set up of the equipment. We retrospectively studied 70 patients who underwent LUS during their laparoscopic cholecystectomy operation over a period of 31 months. Data about preoperative investigation, intraoperative findings, and postoperative outcome were retrospectively collected and analyzed. LUS was found to be quick, safe, and effective in the intraoperative diagnosis of the common bile duct stones. It does not add significantly to the operative time and is inherently safer than intraoperative cholangiogram owing to the fact that it does not involve ionizing radiation. It is also more convenient, as there is no need to wear protective lead to avoid the side effects of ionizing radiation.

Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study.

BACKGROUND: The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. METHODS: We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. RESULTS: Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. CONCLUSION: To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term.

F-18-FDG and C-11-Choline Positron Emission Tomography in Human Esophago-Gastric Cancer: Prediction of Response to Therapy.

BACKGROUND: To determine the utility of F-18-FDG and C-11-Choline uptake, in patients with esophageal and esophago-gastric junction tumors who are to undergo either neo-adjuvant or palliative chemotherapy, in predicting response (pathological and survival). METHODS: Eighteen patients with biopsy proven cancer were recruited prospectively. Patients underwent PET imaging before and during the first cycle of chemotherapy (seven and 14 days) with both F-18-FDG and C-11-Choline. Tracer uptake was quantified using Standardized Uptake Values. Pathological tumor response was determined using the Mandard criteria. Cellular proliferation was determined using ki-67 immunohistochemistry. Relationships between tracer uptake and response, one-year survival and cellular proliferation were determined. RESULTS: All 18 tumors were imaged by F-18-FDG PET compared to 16/18 with C-11-Choline. Change in uptake of either tracer did not correlate with pathological response. Pathological response did not influence survival (median-survival, responders = 16.1 months; non-responders = 19.0 months, p = 0.978). There was no significant correlation of change in tracer uptake with survival. C-11-Choline tumor uptake did not correlate with cellular proliferation. CONCLUSION: F-18-FDG PET is superior for imaging of the primary tumor. Neither F-18-FDG nor C-11-Choline PET was able to predict response accurately.

An enzymatic route to 5-deoxy-5-[18F]fluoro-D-ribose, a [18F]-fluorinated sugar for PET imaging.

An efficient two-step, one-pot, biotransformation involving the fluorinase enzyme is described for the synthesis of 5-deoxy-5-[(18)F]fluororibose, a novel [(18)F]-fluorinated sugar suitable for positron emission tomography (PET) applications.

The effect of comorbidity on quality of life during radiotherapy in head and neck cancer.

OBJECTIVE: To identify the impact of comorbidity on quality of life during radiotherapy in head and neck cancer patients. STUDY DESIGN: Prospective assessment of quality of life and retrospective assessment of comorbidity. SUBJECTS AND METHODS: Patients' quality of life was assessed at the start and twice during radiation treatment with the University of Washington Quality of Life questionnaire. Comorbidity was assessed from the case notes of 91 patients with the Adult Comorbidity Evaluation-27 index. RESULTS: A mean comorbidity burden of 1.07 was found. Comorbid illnesses afflicted a little more than 60 percent of our cohort. Patients with moderate to severe comorbidity had statistically significantly worse quality of life at the start (P = 0.044) and midpoint of treatment (P = 0.005), but not at the end of treatment (P = 0.114). The magnitude of change of these scores after treatment was not influenced by comorbidity. CONCLUSION: On the basis of severity of decompensation, radiotherapy does not produce a differential impact on the quality of life.

Analysis of complications following surgical treatment of benign parotid disease.

BACKGROUND: The objective of the study was to study the incidence of, and risk factors for developing complications following parotidectomy for benign disease, to improve preoperative patient counselling and better inform future surgical management. METHODS: An 11-year retrospective review of 162 parotidectomies for benign disease, collecting and analysing data about presentation, investigations, surgical treatment, postoperative facial nerve function, Frey's syndrome and other surgical complications. RESULTS: The mean age at presentation was 58 years. The commonest pathology was benign pleomorphic adenoma (43%), followed by Warthin's tumour (30%) and chronic sialadenitis (22%). Sialadenitis was a significant risk factor for facial nerve palsy and increased the incidence of salivary fistulas. Parotid duct ligation increased the risk of nerve palsy in the distribution of zygomatic and buccal branches. Operations for Warthin's tumour were associated with an increased risk of dysfunction of the cervical branch of the nerve. Half the patients had intraoperative facial nerve stimulation and this did not influence the likelihood of facial paresis. The recovery of facial nerve function showed a biphasic distribution, with 90% of patients having normal function within 12 months, followed by a slower recovery rate for up to 2 years. CONCLUSION: The incidence of postoperative complications was influenced by the pathology, with inflammatory lesions significantly increasing the risk of facial nerve dysfunction and other complications, but also by variations in surgical practice, such as parotid duct ligation. Overall, the incidence of permanent facial paralysis was less than 2%, but temporary nerve palsy was common at 40%, with most patients regaining normal function within 1 year of the operation.

Monitoring primary breast cancer throughout chemotherapy using FDG-PET.

UNLABELLED: We have compared 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography (FDG-PET) images of large or locally advanced breast cancers (LABC) acquired during Anthracycline-based chemotherapy. The purpose was to determine whether there is an optimal method for defining tumour volume and an optimal imaging time for predicting pathologic chemotherapy response. METHOD: PET data were acquired before the first and second cycles, at the midpoint and at the endpoint of neoadjuvant chemotherapy. FDG uptake was quantified using the mean and maximum standardized uptake values (SUV) and the coefficient of variation within a region of interest. Receiver-operator characteristic (ROC) analysis was used to determine the discrimination between tumours demonstrating a high pathological response (i.e. those with greater than 90% reduction in viable tumour cells) and low pathological response. RESULTS: Only tumours with an initial tumour to background ratio (TBR) of greater than five showed a difference between response categories. In terms of response discrimination, there was no statistically significant advantage of any of the methods used for image quantification or any of the time points. The best discrimination was measured for mean SUV at the midpoint of therapy, which identified 77% of low responding tumours whilst correctly identifying 100% of high responding tumours and had an ROC area of 0.93. CONCLUSION: FDG-PET is efficacious for predicting the pathologic response of most primary breast tumours throughout the duration of a neoadjuvant chemotherapy regimen. However, this technique is ineffective for tumours with low image contrast on pre-therapy PET scans.