Evaluation of Dilution Susceptibility Testing Methods for Aztreonam in Combination with Avibactam against Enterobacterales.

As multidrug and pan-resistance among Enterobacterales continue to increase, there is an urgent need for more therapeutic options to treat these infections. New ß-lactam and ß-lactam inhibitor (BLI) combinations have a broad spectrum of activity, but those currently approved do not provide coverage against isolates harboring metallo-ß-lactamases (MBL). Aztreonam (ATM) and avibactam (AVI) in combination (ATM/AVI; AVI at 4 µg/mL fixed concentration) provides a similarly broad range of activity while maintaining activity against MBL-producing isolates. The in vitro susceptibility testing of ATM/AVI by standard methods was evaluated during development. This study investigated the impact of nonstandard testing conditions on the activity of ATM/AVI as observed during broth microdilution testing as well as the equivalency between agar dilution and broth microdilution MIC values when testing a diverse panel of Enterobacterales (N = 201). Nonstandard test conditions evaluated included inoculum density, atmosphere of incubation, media pH, varied medium cation concentrations, incubation time, varied serum concentrations, testing in pooled urine instead of media, addition of blood to the media, and the presence of surfactant. Generally, apart from low pH and high inoculum density, nonstandard testing parameters did not affect ATM/AVI broth microdilution MIC values. Correlation of MIC values obtained by agar dilution and broth microdilution resulted in an essential agreement of 97.0% for all tested Enterobacterales. Variation of standard testing conditions had little impact on broth microdilution MIC values for ATM/AVI. The correlation between broth microdilution and agar dilution MICs suggests both methods are reliable for determination of ATM/AVI MIC values. IMPORTANCE Increasing antibiotic resistance and emergence of pan-resistant isolates threaten the ability to control infections and to provide many other medical interventions such as surgery and chemotherapy, among others. New therapies are required to control emerging resistance mechanisms, including the increase in metallo-ß-lactamases. Some new antibiotic combinations provide coverage against highly resistant isolates but are unable to target organisms that produce metallo-ß-lactamases. Aztreonam in combination with avibactam provides a broad spectrum of activity against highly resistant isolates that also targets metallo-ß-lactamase-producing organisms. An important part of drug development is the ability for clinical labs to determine the susceptibility of isolates to the antimicrobial. This manuscript investigates the in vitro susceptibility testing of aztreonam/avibactam with nonstandard testing conditions and a correlation study between broth microdilution and agar dilution against clinical isolates encoding a variety of resistance mechanisms. Overall, aztreonam/avibactam was generally unaffected by changes in testing conditions and showed strong agar/broth correlation.

Use of the Veggie Meter® as a tool to objectively approximate fruit and vegetable intake among youth for evaluation of preschool and school-based interventions.

BACKGROUND: Reflection spectroscopy is an emerging, non-invasive objective measure used to approximate fruit and vegetable intake. The present study aimed to use a reflection spectroscopy device (the Veggie Meter®, Longevity Link Corporation, Salt Lake City, UT, USA) to assess skin carotenoid status in preschool, middle- and high-school students and to examine associations between skin carotenoids and self-reported dietary intake. METHODS: In Autumn 2018, we used the Veggie Meter® to assess skin carotenoids and age-appropriate validated dietary assessment measures to approximate fruit and vegetable (FV) intake. Preschool participants completed a previously validated pictorial liking tool using an iPad (Apple Inc., Cupertino, CA, USA). Middle-school participants completed selected questions from the validated School Physical Activity and Nutrition (SPAN) (Michael & Susan Dell Center for Healthy Living, University of Texas, Austin, TX, USA) questionnaire regarding frequency of their FV and beverage intake on the previous day, with additional questions about physical activity. High-school participants' FV intake was assessed using the Fruit and Vegetable Screener (National Cancer Institute, Bethesda, MD, USA). Spearman correlation coefficients were used to determine bivariate associations between measures of dietary intake and Veggie Meter®-assessed skin carotenoid levels. RESULTS: Mean (SD) Veggie Meter® readings were 266 (82.9), 219 (68.1) and 216 (67.2) among preschool, middle- and high-school students. There was an inverse association between soda intake and Veggie Meter® readings (r = -0.22, P = 0.03) among middle-school students; and a positive association between daily fruit intake and Veggie Meter® readings (r = 0.25, P = 0.06) among high-school students. CONCLUSIONS: The Veggie Meter® comprises a promising evaluation tool for preschool and school-based nutrition interventions.

Inguinal herniae: Valuable clues to concurrent abdominal pathology: A series of case studies describing unusual findings in 'routine' hernia operations which demonstrate the need for thorough surgical training.

INTRODUCTION: The case series presented here demonstrates that the pathology encountered during inguinal hernia repair can often provide clues to concurrent pathology; the well trained surgeon's broader medical knowledge can lead to earlier diagnosis. PRESENTATION OF CASES: The case series examines four cases of men presenting with inguinal hernias, who were found to have concurrent abdominal pathology after further investigation of the intraoperative findings of the surgeon. DISCUSSION: Operating surgeons not only require the necessary surgical skills to deal with the unexpected, but must also rely on their ability to think laterally when interpreting atypical incidental findings during 'routine' procedures. CONCLUSION: Experience and knowledge gained through a surgeon's career is essential to enable them to correctly interpret their intraoperative findings and potentially diagnose concurrent pathology. The authors believe that surgical care practitioners, trained in just 2 years, would lack these essential skills.

Fat necrosis of the breast--a review.

Fat necrosis of the breast is a benign condition that most frequently affects peri-menopausal women. It can mimic breast cancer clinically or radiologically. In other cases it can obscure malignant lesions. The core of this review is derived from a MEDLINE database literature search from 1966-2004. Further references were from lateral search. In this paper, we review the pathogenesis and pathology clinical and radiological features of fat necrosis of the breast. The implication of fat necrosis in the management of patients with breast lump is also discussed. Fat necrosis of breast is a complex process. Therefore, a systematic review of this condition will enable surgeons, radiologists and oncologists working in the field of breast disease to understand it better and improve its management.

Electronic absorption and emission spectral data and fluorescence quantum yields of bridgedp-oligophenylenes, bi- to deciphenyls, and related furans and carbazoles.

Absorption and fluorescence emission spectral data, as well as fluorescence quantum yields (Φf), were determined for 41p-oligophenylene compounds containing 2-6, 8, and 10 benzene rings. Of 29 compounds containing carbon-bridged rings (fluorenes), 28 were dialkylated on each bridge for improved solubility and photostability. Absorption maxima for oligophenylenes were observed at wavelengths as long as 366 nm, emission maxima to 437 nm, and molar extinction coefficients (ɛ) as large as 153,000 L/mol-cm; all three exceeded predicted maximum values for the corresponding unbridged oligophenylenes. The substitution of furan for benzene or carbazole for a fluorene (two examples each) bathochromically shifted absorption and emission maxima. Dialkylated carbon bridges bathochromically shifted absorption and emission maxima, and lowered Φf in biphenyl and in one terphenyl analogue, but appeared to cause no diminution of Φf in higher oligophenylenes. Bis(2-methoxyethyl) substitution on the bridges, incorporated to provide solubility in polar solvents, lowered Φf in all examples. Tertiary alkyl substituents on terminal rings bathochromically shifted the absorption and emission maxima and generally increased Φf. The "loose bolt" effect, which lowers Φf in mononuclear substituted benzenes, may operate in 9,9-dialkylfluorenes, but not in 2,7-di-t-butylfluorene or in higher oligophenylenes. Cyclic ether and methoxy substituents as auxofluors on terminal rings generally bathochromically shifted absorption and emission maxima and increased ɛ and Φf. Cyano substituents bathochromically shifted absorption and emission maxima, and increased ɛ, but lowered Φf slightly.

The role of instructional set on alcoholic performance.

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.

A deficit of bladder cancer in an Asian community in the UK.

Over a 10-year period, the incidence of bladder cancer in the local Asian community living within the Ealing hospital catchment area was compared with that in the indigenous population and that in England and Wales. A significantly reduced incidence was seen in the Asian community, using both comparisons.

Study of the effectiveness of bupivicaine infiltration of the ilioinguinal nerve at the time of hernia repair for post-operative pain relief.

The effect on post-operative pain relief and analgesic requirements of direct ilioinguinal nerve block using 0.5% bupivicaine (Marcain) at the time of hernia repair was studied. Sixty patients were randomly allocated into two groups, A and B, both being well matched for age, numbers and sex. Those in whom nerve block was used (Group A) required significantly less intramuscular opiates and strong oral analgesics (co-dydramol) than those who did not receive bupivicaine (Group B) during the first 24 hours post-operatively.

Liver atrophy complicating benign bile duct strictures. Surgical and interventional radiologic approaches.

The hepatic atrophy and hypertrophy complex has been described in a selected group of nine patients with benign bile duct stricture. The clinical features common to this group were a high biliary stricture and a long-standing history of cholangitis and intermittent jaundice. A history of multiple surgical procedures and associated vascular damage or portal hypertension is strongly suggestive of the atrophy and hypertrophy complex. The radiologic criteria for the diagnosis of this condition are presented. Computerized tomography and HIDA scintigraphy were valuable as noninvasive means to diagnose lobar liver atrophy. The atrophy and hypertrophy complex described herein poses significant therapeutic problems and demands approaches other than those normally applicable for high biliary strictures. A combined surgical and radiologic approach with additional interventional radiologic procedures may be appropriate in patients in whom hilar anastomosis is difficult or impossible.

Colonoscopy related endotoxemia.

A pilot study of 20 patients who underwent colonoscopy was performed to investigate the occurrence of endotoxemia related to the procedure and its clinical significance. With the use of the limulus lysate method of assay, endotoxemia was demonstrated in 25 per cent of the patients during colonoscopy and 65 per cent afterwards, but was not associated with either concomitant bacteremia or any ill effects. The appearance of endotoxin in significant concentration in the presence of normal liver function and with no overt focus of infection, suggests that substantial absorption of bacterial products which originate in the intestine occur, but under normal circumstances cause no demonstrable deleterious effects.

Per-operative cholangiography and post-cholecystectomy biliary strictures.

A series of 78 patients with post-cholecystectomy biliary strictures have been examined. The majority (71%) did not have per-operative cholangiography at the time of initial cholecystectomy. Of the remainder, inadequate views were obtained in two patients and incomplete information was associated with subsequent common bile duct damage. In addition the study was performed after the common bile duct had been transected in a further two cases. The use of per-operative cholangiography in patients undergoing cholecystectomy is advocated, and the advantages and disadvantages of such an approach examined.

Benign bile duct stricture following cholecystectomy: critical factors in management.

Seventy-eight patients with benign bile duct stricture following cholecystectomy were referred for further management over an 8-year period. The majority (58 per cent) had multiple operations before referral. On presentation 90 per cent of patients had abnormal liver function tests, 19.5 per cent a depressed serum albumin, 49 per cent a history of previous major infection, and 14 per cent associated liver disease and portal hypertension. Seventy-two patients (92 per cent) were operated upon: 63 by stricture repair alone, 4 by stricture repair and portal systemic anastomosis, and one by splenorenal anastomosis alone. Of the patients treated by stricture repair alone and no other procedure 90 per cent have a good result with a mean follow-up of 3.3 years, and an operative (30-day) mortality of 3.2 per cent. There were no postoperative deaths in 61 patients in whom stricture repair alone was performed by direct suture techniques, but in the presence of portal hypertension and liver disease the mortality was 27 per cent. Factors influencing a satisfactory stricture repair were the number of previous operations, site of stricture and type of repair. Factors influencing mortality were the number of previous operations, a history of major infection, the site of stricture, pre-operative serum albumin concentration, and the presence of liver disease and portal hypertension.