Bisphosphonate Versus Bisphosphonate and Calcitonin for the Treatment of Moderate to Severe Hypercalcemia of Malignancy.

BACKGROUND: Historically, intravenous (IV) bisphosphonates with calcitonin are the treatment of choice for hypercalcemia of malignancy. However, evidence is lacking. OBJECTIVE: The objective of this study was to compare the use of bisphosphonate versus bisphosphonate with calcitonin for moderate to severe hypercalcemia of malignancy. METHODS: This was a retrospective study evaluating patients who received bisphosphonate and/or calcitonin for treatment of moderate to severe hypercalcemia of malignancy. Patients received usual care plus either (1) bisphosphonate or (2) bisphosphonate with calcitonin. The primary outcome was change in corrected serum calcium concentrations 48 hours after treatment. Secondary outcomes included corrected calcium levels, incidence of normocalcemia and hypocalcemia, time to normocalcemia, hospital length of stay, and cost avoidance. RESULTS: The 48-hour decrease in corrected calcium was less in the bisphosphonate group than in the combination group (2.4 [1.6-3.4] vs 3.9 [3.5-5.3]; P < 0.001). However, initial calcium levels in the combination group were higher than in the bisphosphonate group, and calcium levels at 24, 48, and 72 hours were similar. Secondary outcomes did not differ. Average cost avoidance with bisphosphonate monotherapy was $11 248 per patient and $291 448 per year. CONCLUSIONS AND RELEVANCE: In the treatment of moderate to severe hypercalcemia of malignancy, IV bisphosphonate in combination with calcitonin resulted in a higher difference in corrected calcium levels at 48 hours compared with bisphosphonate therapy alone. However, corrected calcium levels in the first 72 hours, time to normocalcemia, and clinical outcomes were similar. The addition of calcitonin increases cost without substantial clinical benefit, and providers may consider avoiding calcitonin.

Validity Of Transabdominal Ultrasound Scan In The Prediction Of Uterine Scar Thickness.

BACKGROUND: Caesarean section rate is increasing throughout the world, which increases the risk of complications in subsequent pregnancy with increased maternal and foetal morbidity and mortality. There is risk of uterine rupture in subsequent pregnancy with trial of labour after caesarean section (TOLAC). Therefore, accurate prediction of uterine rupture can be of significant value during the management of subsequent pregnancies after previous caesarean delivery. The aim of this study was to evaluate the accuracy of prenatal transabdominal sonography in determining the lower uterine segment thickness in women with previous caesarean section, to document relevant risk factors in the obstetric history of subjects predisposing to uterine scar rupture and to define a cut-off value of uterine thickness for prediction of uterine rupture. METHODS: This cross-sectional validation study was conducted in the Department of Obstetrics and Gynaecology, Ayub Teaching Hospital, Abbottabad from May to October 2017.Transabdominal ultrasound was carried out in all patients before labour for the measurement of uterine scar thickness. Patients were followed till caesarean section and intraoperative findings were recorded. RESULTS: A total of 117 patients were enrolled. Out of these 33% had thin or dehiscence/rupture scar. At the cut-off value of ≤5 mm the sensitivity was 76.9%, specificity 48.7% and accuracy was 58.12%. No significant association was found between clinical features and scar dehiscence/rupture. CONCLUSIONS: No definite USG cut-off limit could be established to provide guidance regarding the clinical decision of opting for VBAC or repeat caesarean/section; scar thicknesses ≤5.0 mm should be judged cautiously.

Effect of Cefepime on Neurotoxicity Development in Critically Ill Adults With Renal Dysfunction.

BACKGROUND: Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events. RESEARCH QUESTION: What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction? STUDY DESIGN AND METHODS: Critically ill adults with creatinine clearance < 60 mL/min who received cefepime for ≥ 48 hours between January 1, 2014 and July 31, 2018 were evaluated for cefepime-associated neurotoxicity (CAN) development. Higher- and lower-dose cefepime exposure groups stratified by moderate (≥ 8 g vs < 8 g in first 48 hours) or severe (≥ 4 g vs < 4 g in first 48 hours) renal dysfunction were compared. Between-group comparisons were performed using Fisher exact tests. CAN-free survival was evaluated using Kaplan-Meier curves and log-rank tests. RESULTS: Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6 g vs 7.7 ± 2.2 g; P < .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n = 108) and higher-dose (n = 92) cefepime groups (4% vs 10%, OR 2.82, 95% CI, 0.84-9.48, P = .093). The frequencies of cefepime-associated neurotoxicity were similar between lower- and higher-dose cefepime groups when moderate renal dysfunction subgroups were compared (5% vs 7%, OR 1.42, 95% CI, 0.34-5.92, P = .72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs 16%, P = .064). Times to cefepime-associated neurotoxicity development and resolution were similar between lower- and higher-dose groups. Durations of CAN-free survival were similar between lower- and higher-dose groups. Most patients who developed cefepime-associated neurotoxicity displayed altered mental status (n = 12, 92%). INTERPRETATION: Cefepime-associated neurotoxicity is an uncommon occurrence in critically ill adults. Patients with severe renal dysfunction receiving higher-dose cefepime may be at greater risk of cefepime-associated neurotoxicity, although this requires additional investigation.

Over-expression, purification, and confirmation of Bacillus anthracis transcriptional regulator NprR.

Quorum sensing (QS) has been recognized as an important biological phenomenon in which bacterial cells communicate and coordinate their gene expression and cellular processes with respect to population density. Bacillus anthracis is the etiological agent of fatal pulmonary anthrax infections, and the NprR/NprX QS system may be involved in its pathogenesis. NprR, renamed as aqsR for anthrax quorum sensing Regulator, is a transcriptional regulator that may control the expression of genes required for proliferation and survival. Currently, there is no protocol reported to over-express and purify B. anthracis AqsR. In this study, we describe cloning, purification, and confirmation of functional full-length B. anthracis AqsR protein. The AqsR gene was cloned into the pQE-30 vector with an HRV 3C protease recognition site between AqsR and the N-terminal His6-tag in order to yield near native AqsR after the His-tag cleavage, leaving only two additional amino acid residues at the N-terminus.