Background
The use of laparoscopy-assisted distal gastrectomy (LADG) in advanced gastric cancer (AGC) remains a controversial topic, mainly because of doubts about its oncologic validity. To date, ...literature on the prognosis for AGC after LADG is scarce. This study evaluated the procedure’s long-term benefits compared with those of the conventional, open distal gastrectomy (ODG).
Methods
This study involved 201 patients, 66 of whom underwent LADG, with a mean follow-up period of 49.2 months, from January 1999 to March 2010. A clear set of criteria was used to select patients (including no evidence of lymph node metastasis) and surgeons (subject to their experience). Survival outcomes were assessed by Kaplan–Meier analysis and log-rank testing. The postoperative recovery and complications of the patients also were monitored.
Results
No significant difference was observed between LADG and ODG in terms of overall survival or disease-specific survival. The corresponding 5-year survival rates for individual tumor node metastasis stages also were comparable in each group. The number of lymph nodes harvested was similar in the two groups, although the operation time was significantly shorter for ODG. The postoperative hospital stay was shorter for LADG patients (average stay of 8.4 vs. 18.1 days in the ODG group;
p
< 0.001), and the postoperative complication rate was almost half that for ODG (13.6 vs. 25.0 %;
p
= 0.048).
Conclusion
The combination of the long- and short-term data indicates that LADG should be considered as a feasible alternative to ODG for the treatment of AGC. Its widespread integration requires the accumulation of similar results across multiple centers worldwide.
Introduction: It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) ...is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. Methods: Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement 1 year apart. Patients were divided into two groups (“high” vs. “low”) by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality, respectively. Results: After a median of follow-up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p = 0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p = 0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR: 1.74, 95% CI: 1.09–2.79, p = 0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. Conclusions: While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome.
Concerns have been raised that a lack of senior obstetricians ("consultants") on the labour ward outside normal hours may lead to worse outcomes among babies born during periods of reduced cover.
We ...carried out a multicentre cohort study using data from 19 obstetric units in the United Kingdom between 1 April 2012 and 31 March 2013 to examine whether rates of obstetric intervention and outcome change "out-of-hours," i.e., when consultants are not providing dedicated, on-site labour ward cover. At the 19 hospitals, obstetric rotas ranged from 51 to 106 h of on-site labour ward cover per week. There were 87,501 singleton live births during the year, and 55.8% occurred out-of-hours. Women who delivered out-of-hours had slightly lower rates of intrapartum caesarean section (CS) (12.7% versus 13.4%, adjusted odds ratio OR 0.94; 95% confidence interval CI 0.90 to 0.98) and instrumental delivery (15.6% versus 17.0%, adj. OR 0.92; 95% CI 0.89 to 0.96) than women who delivered at times of on-site labour ward cover. There was some evidence that the severe perineal tear rate was reduced in out-of-hours vaginal deliveries (3.3% versus 3.6%, adj. OR 0.92; 95% CI 0.85 to 1.00). There was no evidence of a statistically significant difference between out-of-hours and "in-hours" deliveries in the rate of babies with a low Apgar score at 5 min (1.33% versus 1.25%, adjusted OR 1.07; 95% CI 0.95 to 1.21) or low cord pH (0.94% versus 0.82%; adjusted OR 1.12; 95% CI 0.96 to 1.31). Key study limitations include the potential for bias by indication, the reliance upon an organisational measure of consultant presence, and a non-random sample of maternity units.
There was no difference in the rate of maternal and neonatal morbidity according to the presence of consultants on the labour ward, with the possible exception of a reduced rate of severe perineal tears in out-of-hours vaginal deliveries. Fewer women had operative deliveries out-of-hours. Taken together, the available evidence provides some reassurance that the current organisation of maternity care in the UK allows for good planning and risk management. However there is a need for more robust evidence on the quality of care afforded by different models of labour ward staffing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vascular co-option is a resistance mechanism to anti-angiogenic agents, but combinations of anti-vascular agents may overcome this resistance. We report a phase 1b and randomised phase 2 trial to ...determine the safety and efficacy of pazopanib with fosbretabulin.
Eligible patients had recurrent, epithelial ovarian cancer with a platinum-free interval (PFI) of 3 to 12 months. Patients were stratified according to PFI (>6 versus ≤6 months) and prior bevacizumab use.
Twelve patients were treated in the phase 1b. Commonest grade ≥ 2 adverse events (AEs) were hypertension (100%), neutropenia (50%), fatigue (50%), vomiting (50%). There was one DLT (grade 3 fatigue). The recommended phase 2 dose level was fosbretabulin 54 mg/m2 on days 1, 8 and 15 and pazopanib 600 mg once daily (od), every 28 days, which was then compared to pazopanib 800 mg od in a randomised phase 2 trial. Twenty-one patients were randomised (1:1) in the phase 2 trial. In phase 1b and phase 2, four patients treated with pazopanib and fosbretabulin developed reversible, treatment-related cardiac AEs, leading to premature discontinuation of the study. In the phase 2 trial, the median PFS was 7.6 months (95% CI 4.1-not estimated) versus 3.7 months (95% CI 1.0–8.1) in favour of the experimental arm (HR 0.30, 95% CI 0.09–1.03, P = .06).
It remains unclear whether pazopanib with with fosbretabulin is an efficacious regimen to treat epithelial ovarian cancer. Effective cardiac risk mitigation is needed to increase the tolerability and maximize patient safety in future trials.
•First trial investigating pazopanib plus fosbretabulin in relapsed ovarian cancer.•The median PFS and OS favoured pazopanib plus fosbretabulin versus pazopanib alone.•Pazopanib plus fosbretabulin was associated with reversible cardiac toxicity.•The trial was discontinued due to cardiac toxicity in the experimental arm.
Aim
Few investigators have considered the possibility that skeletal muscles might contain thermosensitive elements capable of modifying thermoeffector responses. In this experiment, the temporal ...relationships between dynamic changes in deep‐body and intramuscular temperatures and eccrine sweat secretion were explored during rhythmical and reproducible variations in heat production.
Methods
Eight subjects performed semi‐recumbent cycling (25 °C) at a constant load to first establish whole‐body thermal and sudomotor steady states (35 min), followed by a 24‐min block of sinusoidal workload variations (three, 8‐min periods) and then returning to steady‐state cycling (20 min). Individual oesophageal, mean skin and intramuscular (vastus lateralis) temperatures were independently cross‐correlated with simultaneously measured forehead sweat rates to evaluate the possible thermal modulation of sudomotor activity.
Results
Both intramuscular and oesophageal temperatures showed strong correlations with sinusoidal variations in sweating with respective maximal cross‐correlation coefficients of 0.807 (±0.044) and 0.845 (±0.035), but these were not different (P = 0.40). However, the phase delay between intramuscular temperature changes and sweat secretion was significantly shorter than the delay between oesophageal temperature and sweating 25.6 s (±12.6) vs. 46.9 s (±11.3); P = 0.03.
Conclusion
The temporal coupling of eccrine sweating to intramuscular temperature, combined with a shorter phase delay, was consistent with the presence of thermosensitive elements within skeletal muscles that appear to participate in the modulation of thermal sweating.
Health Care in Times of War Shen, Gordon C.; Martelli, Peter F.; Clarke, Paul Knox ...
Academy of Management perspectives,
05/2022, Letnik:
36, Številka:
2
Journal Article
Recenzirano
Many countries face cycles of repeated violence. Attacks on health workers and facilities exact a toll on civilian access to care and, in aggregate, population health status. A variety of ...humanitarian organizations provide essential services to augment limited state capacity. Yet, humanitarian organizations often work in parallel even in the same conflict-affected contexts. We use a high-reliability organization lens to examine violent attacks on the health care programs that humanitarian organizations operate in fragile states. More specifically, we examine an extant construct of coupling through qualitative evidence of collaborative relationships and creative problem-solving under stressful conditions. We find three salient features from qualitative data: trade-off between security and field access, transfer of risk to local actors, and marketization of aid. We find that these three features drive humanitarian organizations to act nimbly within countries to prioritize their organizational reliability across countries. While stabilizing the individual organization, these features create disincentives to interorganizational coordination at the cluster level and are agnostic to output (i.e., health care provision) reliability. We hope our study will sensitize readers to several issues facing high-reliability health care in times of war.
Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for nicotinamide adenine dinucleotide (NAD
+
) biosynthesis in mammalian cells. NAMPT inhibitors represent multifunctional anticancer agents ...that act on NAD
+
metabolism to shut down glycolysis, nucleotide biosynthesis, and ATP generation and act indirectly as PARP and sirtuin inhibitors. The selectivity of NAMPT inhibitors preys on the increased metabolic requirements to replenish NAD
+
in cancer cells. Although initial clinical studies with NAMPT inhibitors did not achieve single-agent therapeutic levels before dose-limiting toxicities were reached, a new understanding of alternative rescue pathways and a biomarker that can be used to select patients provides new opportunities to widen the therapeutic window and achieve efficacious doses in the clinic. Recent work has also illustrated the potential for drug combination strategies to further enhance the therapeutic opportunities. This review summarizes recent discoveries in NAD
+
/NAMPT inhibitor biology in the context of exploiting this new knowledge to optimize the clinical outcomes for this promising new class of agents.
Learning disabilities have profound, long-lasting health sequelae. Affected children born over the course of 1 year in the United States of America generated an estimated lifetime cost of $51.2 ...billion. Results from some studies have suggested that autistic spectrum disorder may vary by season of birth, but there have been few studies in which investigators examined whether this is also true of other causes of learning disabilities. We undertook Scotland-wide record linkage of education (annual pupil census) and maternity (Scottish Morbidity Record 02) databases for 801,592 singleton children attending Scottish schools in 2006-2011. We modeled monthly rates using principal sine and cosine transformations of the month number and demonstrated cyclicity in the percentage of children with special educational needs. Rates were highest among children conceived in the first quarter of the year (January-March) and lowest among those conceived in the third (July-September) (8.9% vs 7.6%; P < 0.001). Seasonal variations were specific to autistic spectrum disorder, intellectual disabilities, and learning difficulties (e.g., dyslexia) and were absent for sensory or motor/physical impairments and mental, physical, or communication problems. Seasonality accounted for 11.4% (95% confidence interval: 9.0, 13.7) of all cases. Some biologically plausible causes of this variation, such as infection and maternal vitamin D levels, are potentially amendable to intervention.
Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to ...distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments.
Methods
All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians.
Results
Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections.
Conclusions
Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.
We evaluated characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection and persistent RNA detection using genomic, clinical, and laboratory assessments. Despite overall good concordance among these 3 approaches in identifying persistent RNA detection, clinical and laboratory assessments failed to identify 33% of genomically supported reinfections.
Meeting ambitious climate targets will require deploying the full suite of mitigation options, including those that indirectly reduce greenhouse-gas (GHG) emissions. Healthy diets have sustainability ...co-benefits by directly reducing livestock emissions as well as indirectly reducing land use emissions. Increased crop productivity could indirectly avoid emissions by reducing cropland area. However, there is disagreement on the sustainability of proposed healthy U.S. diets and a lack of clarity on how long-term sustainability benefits may change in response to shifts in the livestock sector. Here, we explore the GHG emissions impacts of seven scenarios that vary U.S. crop yields and healthier diets in the U.S. and overseas. We also examine how impacts vary across assumptions of future ruminant livestock productivity and ruminant stocking density in the U.S. We employ two complementary land use models—the US FABLE Calculator, an agricultural and forestry sector accounting model with high agricultural commodity representation, and GLOBIOM, a spatially explicit partial equilibrium optimization model for global land use systems. Results suggest that healthier U.S. diets that follow the Dietary Guidelines for Americans reduce agricultural and land use greenhouse gas emissions by 25–57% (approx 120–310 MtCO
2e
/y) and pastureland area by 28–38%. The potential emissions and land sparing benefits of U.S. agricultural productivity growth are modest within the U.S. due to the increasing comparative advantage of U.S. crops. Our findings suggest that healthy U.S. diets can significantly contribute toward meeting U.S. long-term climate goals for the land use sectors.
PDF
