Background
Use of topical antibiotics to improve perineal wound healing after abdominoperineal resection (APR) is controversial. The aim of this systematic review was to determine the impact of local ...application of gentamicin on perineal wound healing after APR.
Methods
The electronic databases Pubmed, EMBASE, and Cochrane library were searched in January 2015. Perineal wound outcome was categorized as infectious complications, non-infectious complications, and primary perineal wound healing.
Results
From a total of 582 articles, eight studies published between 1988 and 2012 were included: four randomized controlled trials (RCTs), three comparative cohort studies, and one cohort study without control group. Gentamicin was administered using sponges (
n
= 3), beads (
n
= 4), and by local injection (
n
= 1). There was substantial heterogeneity regarding underlying disease, definition of outcome parameters and timing of perineal wound evaluation among the included studies, which precluded meta-analysis with pooling. Regarding infectious complications, three of six evaluable studies demonstrated a positive effect of local application of gentamicin: one of four RCTs and both comparative cohort studies. Only two RCTs reported on non-infectious complications, showing no significant impact of gentamicin sponge. All three comparative cohort studies demonstrated a significantly higher percentage of primary perineal wound healing after local application of gentamicin beads, but only one out of three evaluable RCTs did show a positive effect of gentamicin sponges.
Conclusion
Currently available evidence does not support perineal gentamicin application after APR.
Achieving undetectable MRD (U-MRD) status after chemoimmunotherapy predicts longer progression-free and overall survival. The predictive factors and timing of relapse in patients with U-MRD and value ...of interim MRD analysis are ill-defined. This was a prospective study of 289 patients with CLL treated first-line with FCR. MRD analysis was performed after course 3 (C3) and at end of therapy (EOT) in bone marrow using 4-color flow cytometry (sensitivity 10
). Eighteen percent of patients had U-MRD after C3 and 48% at EOT. U-MRD status at EOT was associated with longer PFS (median NR vs 38 mo, p < 0.001). MRD level (≤1% vs >1%) after C3 predicted greater likelihood of U-MRD status at EOT (64% vs 9%, p < 0.001). PFS was significantly longer for patients with MRD ≤1% vs >1% after C3 (median 73 mo vs 41 mo, p < 0.001), but similar for <0.01% vs 0.01-1%. Interim MRD status may therefore be used for risk stratification and to individualize therapy. Eighty-five patients with U-MRD status at EOT had yearly blood MRD monitoring; MRD re-emerged in 38/85, a median of 48 mo after EOT and preceded clinical progression by a median of 24 months, which may allow development of early intervention strategies.
To assess the relationships between bone mineral density (BMD) at the lumbar spine and femoral neck and menopausal status, age, physical variables, and lifestyle and gynecological factors. BMD and ...follicle-stimulating hormone (FSH), estradiol and inhibin levels were measured in 167 women born in Australia, aged 46-57 years, who had no record of receiving hormone replacement therapy. Using the premenopausal group as a baseline, the FSH level was higher in periand postmenopausal subjects (p<0.0005), and estradiol and inhibin levels in the postmenopausal women were lower (p<0.0005). Mean () lumbar spine and femoral neck BMD were 15 3% and 10 3% lower, respectively, in postmenopausal than in premenopausal women. Lumbar spine BMD decreased with increasing age in perimenopausal women only (p<0.005), and femoral neck BMD decreased with increasing age in the pre-, peri-(p<0.05) and postmenopausal women. The difference between femoral neck BMD in the pre-and postmenopausal women was explained by the difference in age between these groups, whereas for lumbar spine BMD the menopausal status was an additional determining factor. There was a negative effect of smoking on femoral neck BMD (p<0.05) in postmenopausal women. In the perimenopausal decade the femoral neck BMD is primarily dependent on age, whereas lumbar spine BMD is dependent on both age and menopausal status.
OBJECTIVE:To determine factors associated with outcomes following pelvic exenteration for advanced nonrectal pelvic malignancy.
BACKGROUND:The PelvEx Collaborative provides large volume data from ...specialist centers to ascertain factors associated with improved outcomes.
METHODS:Consecutive patients who underwent pelvic exenteration for nonrectal pelvic malignancy between 2006 and 2017 were identified from 22 tertiary centers. Patient demographics, neoadjuvant therapy, histopathological assessment, length of stay, 30-day major complication/mortality rate were recorded.The primary endpoints were factors associated with survival. The secondary endpoints included the difference in margin rates across the cohorts, impact of neoadjuvant treatment on survival, associated morbidity, and mortality.
RESULTS:One thousand two hundred ninety-three patients were identified. 40.4% (n = 523) had gynecological malignancies (endometrial, ovarian, cervical, and vaginal), 35.7% (n = 462) urological (bladder), 18.1% (n = 234) anal, and 5.7% had sarcoma (n = 74).The median age across the cohort was 63 years (range, 23–85). The median 30-day mortality rate was 1.7%, with the highest rates occurring following exenteration for recurrent sarcoma or locally advanced cervical cancer (3.3% each). The median length of hospital stay was 17.5 days. 34.5% of patients experienced a major complication, with highest rate occurring in those having salvage surgery for anal cancer.Multivariable analysis showed R0 resection was the main factor associated with long-term survival. The 3-year overall-survival rate for R0 resection was 48% for endometrial malignancy, 40.6% for ovarian, 49.4% for cervical, 43.8% for vaginal, 59% for bladder, 48.3% for anal, and 48.1% for sarcoma.
CONCLUSION:Pelvic exenteration remains an important treatment in selected patients with advanced or recurrent nonrectal pelvic malignancy. The range in 3-year overall survival following R0 resection (40%–59%) reflects the diversity of tumor types.
A precision measurement by AMS of the positron fraction in primary cosmic rays in the energy range from 0.5 to 500 GeV based on 10.9 million positron and electron events is presented. This ...measurement extends the energy range of our previous observation and increases its precision. The new results show, for the first time, that above ∼200 GeV the positron fraction no longer exhibits an increase with energy.
Biodiversity contributes to the ecological and climatic stability of the Amazon Basin
, but is increasingly threatened by deforestation and fire
. Here we quantify these impacts over the past two ...decades using remote-sensing estimates of fire and deforestation and comprehensive range estimates of 11,514 plant species and 3,079 vertebrate species in the Amazon. Deforestation has led to large amounts of habitat loss, and fires further exacerbate this already substantial impact on Amazonian biodiversity. Since 2001, 103,079-189,755 km
of Amazon rainforest has been impacted by fires, potentially impacting the ranges of 77.3-85.2% of species that are listed as threatened in this region
. The impacts of fire on the ranges of species in Amazonia could be as high as 64%, and greater impacts are typically associated with species that have restricted ranges. We find close associations between forest policy, fire-impacted forest area and their potential impacts on biodiversity. In Brazil, forest policies that were initiated in the mid-2000s corresponded to reduced rates of burning. However, relaxed enforcement of these policies in 2019 has seemingly begun to reverse this trend: approximately 4,253-10,343 km
of forest has been impacted by fire, leading to some of the most severe potential impacts on biodiversity since 2009. These results highlight the critical role of policy enforcement in the preservation of biodiversity in the Amazon.
•Cumulative pemetrexed dose is a risk factor for decline in renal function.•Loss of renal function may be associated with increased risk of hematotoxicity.•Long-term adverse events become a greater ...issue with chemo-immunotherapy.
Pemetrexed is a pharmacotherapeutic cornerstone in the treatment of non-small cell lung cancer. As it is primarily eliminated by renal excretion, adequate renal function is essential to prevent toxic exposure. There is growing evidence for the nephrotoxic potential of pemetrexed, which even becomes a greater issue now combined immuno-chemotherapy prolongs survival. Therefore, the aim of this study was to describe the incidence of nephrotoxicity and related treatment consequences during pemetrexed-based treatment.
A retrospective cohort study was conducted in the Jeroen Bosch Hospital, Den Bosch, the Netherlands. All patients that received at least 1 cycle of pemetrexed based therapy were included in the dataset. The primary outcome was defined as a ≥25 % reduction in eGFR. Additionally, the treatment consequences of decreased renal function were assessed. Logistic regression was used to identify risk factors for nephrotoxicity during treatment with pemetrexed.
Of the 359 patients included in this analysis, 21 % patients had a clinically relevant decline in renal function after treatment and 8.1 % of patients discontinued treatment due to nephrotoxicity. Cumulative dose (≥10 cycles of pemetrexed based therapy) was identified as a risk factor for the primary outcome measure (adjusted OR 5.66 (CI 1.73-18.54)).
This study shows that patients on pemetrexed-based treatment are at risk of developing renal impairment. Risk significantly increases with prolonged treatment. Renal impairment is expected to become an even greater issue now that pemetrexed-based immuno-chemotherapy results in longer survival and thus longer treatment duration.
There is a lack of literature evaluating outcomes of the ligament-guided approach in medial unicompartmental knee arthroplasty (UKA). An improved comprehension of the distribution of coronal plane ...alignment of the knee (CPAK) phenotypes and sagittal tibial wear patterns and their associations with patient-reported outcome measures (PROMs) and implant survivorship could provide insights into its further application in daily practice.
A registry was reviewed for patients with a minimal 2-year follow-up who underwent robotic-assisted, ligament-guided, medial UKA between 2008 and 2016. Survivorship and postoperative PROMs were collected. CPAK phenotypes and sagittal tibial wear patterns were determined. Survivorship, Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala and patient satisfaction were compared between phenotypes and sagittal tibial wear patterns.
A total of 618 knees were included at a mean follow-up of 4.1 2.0-9.6 years. Four-year conversion to the TKA survival rate was 98.9% 98.4%-99.3% and 94.3% 93.3%-95.3% for all-cause revision. Patients with preservation of the CPAK phenotype (84.5 ± 14.9, 81.8 ± 15.5, p = 0.033) and restoration of prearthritic coronal alignment (84.1 ± 14.9, 81.7 ± 15.9, p = 0.045) had a significantly higher Kujala score. No other significant differences in survivorship or PROMs were observed between phenotypes or sagittal tibial wear patterns. Additionally, no difference in survival rates was observed between preserved or altered phenotypes.
This study demonstrated that preservation of CPAK phenotype and preservation of prearthritic coronal alignment yielded a significantly higher Kujala score. No other significant differences in PROMs or implant survivorship were observed, suggesting that robotic-assisted, ligament-guided medial UKA provides equal outcomes for all observed phenotypes and sagittal tibial wear patterns in medial compartment OA as long as preoperative CPAK phenotype is preserved postoperatively.
Level III.
This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P‐glycoprotein in human immunodeficiency virus (HIV)‐infected patients receiving an antiretroviral therapy (ART) ...containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics. We measured activities of CYP3A, CYP2D6, and P‐glycoprotein in 28 patients before and during ART using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P‐glycoprotein were tested as covariates. Oral midazolam clearance (overall CYP3A activity) decreased to 0.19‐fold (90% confidence interval (CI), 0.15–0.23), hepatic midazolam clearance and intestinal midazolam availability changed to 0.24‐fold (0.20–0.29) and 1.12‐fold (1.00–1.26), respectively. In CYP2D6 extensive metabolizers, the plasma ratio AUCdextromethorphan/AUCdextrorphan increased to 2.92‐fold (2.31–3.69). Digoxin area under the curve (AUC)0–12 (P‐glycoprotein activity) increased to 1.81‐fold (1.56–2.09). Covariates had no major influence on lopinavir and ritonavir pharmacokinetics. In conclusion, CYP3A, CYP2D6, and P‐glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection.
Clinical Pharmacology & Therapeutics (2008); 84, 1, 75–82 doi:10.1038/sj.clpt.6100452
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