Genetic alterations in many components of the homologous recombination, DNA damage response, and repair (HR-DDR) pathway are involved in the hereditary cancer syndromes, including familial pancreatic ...cancer. HR-DDR genes beyond
,
,
, and
may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC).
We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs. HR-DDR gene mutations were identified and characterized by whole-exome sequencing and whole-genome sequencing. Different HR-DDR gene mutations are associated with variable homologous recombination deficiency (HRD) scores.
Eight of 50 PDACs with at least one HR-DDR gene mutation were identified. One tumor with
mutations is associated with a high HRD score. However, another tumor with a
mutation is associated with a zero HRD score. Notably, four of eight PDACs in this study harbor a
gene mutation. All four
gene mutations were germline mutations. However, currently,
is not the gene panel for germline tests.
The finding in this study thus supports including
in the germline test of HR-DDR pathway genes.
There are currently no data on the relative retention rates of the Instinct clip, Resolution clip, and QuickClip2Long. Also, it is unknown whether retention rate differs when clips are applied to ...ulcerated rather than normal mucosa. The aim of this study is to compare the retention rates of three commonly used endoscopic clips.
Six pigs underwent upper endoscopy with placement of one of each of the three types of clips on normal mucosa in the gastric body. Three mucosal resections were also performed to create "ulcers." Each ulcer was closed with placement of one of the three different clips. Repeat endoscopy was performed weekly for up to 4 weeks.
Only the Instinct and Resolution clips remained attached for the duration of the study (4 weeks). At each time point, a greater proportion of Instinct clips were retained on normal mucosa, followed by Resolution clips. QuickClip2Long had the lowest retention rate on normal mucosa. Similar retention rates of Instinct clips and Resolution clips were seen on simulated ulcers, although both were superior to QuickClip2Long. However, the difference did not reach statistical significance. All QuickClip2Long clips were dislodged at 4 weeks in both the groups.
The Resolution and Instinct clips have comparable retention rates and both appeared to be better than the QuickClip2Long on normal mucosa-simulated ulcers; however this did not reach statistical significance. Both the Resolution clip and the Instinct clip may be preferred in clinical situations when long-term clip attachment is required, including marking of tumors for radiotherapy and anchoring feeding tubes or stents. Either of the currently available clips may be suitable for closure of iatrogenic mucosal defects without features of chronicity.
Ceftazidime is a third generation cephalosporin with a broad range of activity. Clavulanic acid is a β-lactamase inhibitor. A fixed dose combination, with the wide spectrum of action of ceftazidime ...and clavulanic acid's high stability to β-lactamases has been developed by Ranbaxy Laboratories Limited (India). The present study was planned to predict any interaction between ceftazidime and clavulanic acid which could affect the safety and efficacy of the fixed dose combination. The study was an open label, balanced, randomized two-treatment, two-period, two-sequence, crossover, single-dose comparative pharmacokinetic study under fed conditions. A single intravenous injection of the test product containing a fixed dose combination of ceftazidime 2000 mg and potassium clavulanate 200 mg and the reference product containing ceftazidime 2000 mg only, was administered during each period. Serial blood samples were collected until 12 h post-dose in each period. Ceftazidime and clavulanic acid concentration in plasma were determined using two separate LC-MS/MS methods and then pharmacokinetic parameters were evaluated. No significant difference was seen in the mean Tmax, Cmax, AUC0-t, and AUC0-∞ when the drug was administered as ceftazidime alone and in combination with clavulanic acid. The Confidence Intervals for the log transformed parameters Cmax, AUC0-t and AUC0-∞ were within limits of 80-125% of ceftazidime for the test and reference products. The lack of significant difference between the pharmacokinetic parameters for ceftazidime alone and in the presence of clavulanic acid ruled out any significant interaction between ceftazidime and clavulanic acid.
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