Healthcare-associated carbapenem-resistant Klebsiella pneumoniae infections are associated with higher mortality compared to carbapenem-susceptible K. pneumoniae infections in the intensive care unit: a retrospective cohort study.

BACKGROUND: Klebsiella pneumoniae (KP) is an opportunistic pathogen causing severe pneumonia and sepsis. Carbapenem-resistant KP (CRKP) has become a major pathogen in many centres. AIM: To investigate the association between carbapenem resistance and the mortality rate, length of stay, and hospital cost in patients with Klebsiella pneumoniae infection. METHODS: The retrospective cohort study was conducted in the intensive care units of a large teaching tertiary hospital in southwest China between January 1st, 2020 and December 31st, 2022. To examine the impact of carbapenem resistance on mortality rates and economic burden, multivariate Cox regression and generalized linear models were constructed. FINDINGS: The study included 282 adult patients with KP infection (135 CSKP; 147 CRKP). CRKP-infected patients demonstrated higher mortality risk (unadjusted hazard ratio (aHR): 1.980; 95% confidence interval (CI): 1.206-3.248; P = 0.007; aHR: 1.767; 95% CI: 1.038-3.005; P = 0.036) compared to CSKP-infected patients. Stratified analysis, according to type of KP infection, revealed that patients with healthcare-associated CRKP infection had a significantly higher mortality risk compared to those with CSKP infection (log-rank P = 0.015). Patients with CRKP infection had longer hospital stays than those infected with CSKP (adjusted mean: 38.74 vs 29.71 days; P = 0.003), and hospital-related expenses were notably higher among CRKP patients than CSKP patients (adjusted cost: £40,126.73 vs 25,713.74; P < 0.001). CONCLUSION: CRKP infections increase mortality rates, prolong hospital stays, and raise healthcare costs. Healthcare facilities should adopt targeted strategies, including curtailing pre-infection hospitalization periods and managing medications more judiciously.

[Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

[An assessment of the sublingual immunotherapy with Dermatophagoides farinae on asthma control level and pulmonary function of allergic asthma and rhinitis in adult patient].

Objective:To evaluate the efficacy, asthma control level and pulmonary function of sublingual immunotherapy on allergic asthma and rhinitis in adult patient. Method:This retrospective analysis of 182 cases of adult patient from 18-60 years with allergic asthma and rhinitis, according to the patients' wishes they were divided into drug group（66 patients） and SLIT group（116 patients）. Drug group patients were treated with low to moderate doses of inhaled corticosteroids+long-acting ß2 receptor agonists and mometasone furoate nasal spray+desloratadine tablets as symptomatic treatment. SLIT group was treated by SLIT with Dermatophagoides farina drops on this basis. Before treatment and 1 year, 2 year and 3 years after treatment, the ACT, PEF%, DASS, NASS, TNSS and TMS were evaluated. Result:The ACT, PEF%, DASS, NASS, TNSS and TMS had continuously improved significantly 1 year, 2 year and 3 years after treatment in both groups comparing with baseline（P<0.05）. Compared with 1 year after treatment, SLIT group had lower ACT, PEF%, DASS, NASS, TNSS and TMS in 2 years after treatment（all P<0.05）, whereas drug group had lower TMS and DASS（all P<0.05）. In 3 years of treatment, only SLIT group resulted in significant continuous improvement in DASS and TMS（all P<0.05）. After 1 year, 2 and 3 years of treatment, SLIT group resulted in significantly better ACT, PEF%, DASS, NASS and TMS than drug group（all P<0.05）. After 2 and 3 years of treatment, TNSS of SLIT group were significantly lower than in drug group（P<0.05）. Conclusion:Sublingual immunotherapy for 3 yearswith Dermatophagoides farinae dropsin adult patient with allergic asthma and rhinitis was more effective than drug therapy alone, and asthma control and lung function improved significantly.

[Aeroallergen spectrum for patients with allergic rhinitis in Chongqing].

Objective:To determine the distribution characteristics of inhaled allergens and its influencing factors among allergic rhinitis (AR) patients in Chongqing. Method:Intracutaneous test was carried out in 2 474 AR patients. All the cases were divided into six groups according to age, 6-13 years old, >13-18 years old, >18-29 years old, >29-39 years old, >39-49 years old, >49 years old and four groups on the basis of season (spring, summer, autumn, winter). The correlations between the positive rates and gender, age, season were analyzed. Result:The most common allergens were dermatophagoides farin (71.26%), dermatophagoides pteronyssinus (73.61%) and polyvalent insect (60.79%). There was no significant correlation between most allergens and gender(P>0.05). Statistical analysis was conducted among different age groups, it showed that the positive rates of overwhelming majority allergens were highest in the group of 13-18 years old and higher in 6-13 years old group, and then gradually declined with age with a striking difference in each groups (P<0.05). Similar analysis was carried out among the groups in four seasons. It revealed that the prevalence rates of most allergens were higher in summer and autumn than that in spring and winter (P<0.05). Conclusion:Dermatophagoides and polyvalent insect are the most prevalent inhalant allergens in AR disease in Chongqing. Most AR patients had multiple allergens. The prevalence rates of most allergens were significantly different with age and season.

Genome-wide association study confirms that the chromosome Z harbours a region responsible for rumplessness in Hongshan chickens.

Rumplessness in Hongshan chickens has been reported as a novel sex-linked characteristic. Re-sequencing data suggest that a pseudogene on the Z chromosome, LOC431648, is affiliated with this phenotype. In this study, we chose 23 rumpless and 25 normal Hongshan chickens to localize the potential variation by means of a genome-wide association study using a high density microarray. A region on the Z chromosome was found to be closely associated with rumplessness in Hongshan chickens. The region, located in gene LINGO2, was approximately 3 Mb away from pseudogene LOC431648. The function of this gene has not yet been studied in birds. Differential expression of the candidate genes in the tail feather follicles was not detected by q-PCR, which suggests that the rumplessness trait could be attributed to other genetic mechanisms.

An SNP in the MyoD1 gene intron 2 associated with growth and carcass traits in three duck populations.

Myogenic differentiation 1 (MyoD1) genes belong to the MyoD gene family and play key roles in growth and muscle development. This study was designed to investigate the effects of variants in the MyoD1 gene on duck growth and carcass traits. Three duck populations (Cherry Valley, Jingjiang, and Muscovy) were sampled, their growth and carcass traits were measured, and they were genotyped using the PCR-RFLP method. The results showed one novel polymorphism, an alteration in intron 2 of the MyoD1 gene (A to T). It was associated with the traits of weight at 8 weeks, carcass weight, breast muscle weight, leg muscle weight, eviscerated percentage, percentage of leg muscle weight, dressing percentage, and lean meat percentage. This alteration in intron 2 of MyoD1 may be linked with potential major loci or genes affecting some growth and carcass traits.

One novel SNP of growth hormone gene and its associations with growth and carcass traits in ducks.

In this study, the growth hormone (GH) gene was studied as a candidate gene for growth and carcass traits of three duck populations (Cherry Valley duck, Muscovy duck and Jingjiang duck). Three pairs of primers were designed to detect single nucleotide polymorphisms of introns 2, 3 and 4 of the GH gene by polymerase chain reaction-restriction fragment length polymorphism and sequencing methods. Only the products amplified from intron 2 displayed polymorphism. The results showed one novel polymorphism: a variation in intron 2 of GH gene (C172T, JN408701 and JN408702). It was associated with some growth and carcass traits in three duck populations including birth weight, 8-week weight, carcass weight, breast muscle weight, leg muscle weight, eviscerated weight, lean meat rate, dressing percentage, etc. And the TT and CT genotypes were associated with superior growth and carcass traits in carcass weight, dressing percentage and percentage of eviscerated weight. Therefore, the variation in intron 2 of GH may be a molecular marker for superior growth and carcass traits in above duck populations.

Effectiveness of a single 3-mg rasburicase dose for the management of hyperuricemia in patients with hematological malignancies.

Rasburicase was administered at a fixed dose of 3 mg to treat 287 episodes of elevated serum uric acid levels (>7 mg/dL) in 247 adult patients with hematological malignancies. The median total dose of 36 µg/kg (range: 18-65) was a fraction of the recommended total pediatric dose of 0.75-1.0 mg/kg. The median change in uric acid levels at 24 h was -4.1 mg/dL (range: -12 to +1) and -45% (range: -95 to +9). Uric acid levels normalized at 24 h in 72% of patients. There was no relationship between the weight-based dose and uric acid decline. The only predictor of success was the baseline uric acid; the failure rate was 84% with baseline level >12 mg/dL and 18% if it was ≤ 12. Uric acid levels continued to decline beyond 24 h in most patients without additional treatment. Serum creatinine remained stable over 24 h, and declined over 48 h and 7 days. There was no relationship between the extent of reduction in uric acid levels and serum creatinine. We conclude that a single 3-mg dose of rasburicase, used with close monitoring, is sufficient to treat most adults with uric acid levels up to 12 mg/dL.

Reactive oxygen species and uncoupling protein 2 in pancreatic ß-cell function.

Growing evidence indicates that reactive oxygen species (ROS) are not just deleterious by-products of respiratory metabolism in mitochondria, but can be essential elements for many biological responses, including in pancreatic ß-cells. ROS can be a 'second-messenger signal' in response to hormone/receptor activation that serves as part of the 'code' to trigger the ultimate biological response, or it can be a 'protective signal' to increase the levels of antioxidant enzymes and small molecules to scavenge ROS, thus restoring cellular redox homeostasis. In pancreatic ß-cells evidence is emerging that acute and transient glucose-dependent ROS contributes to normal glucose-stimulated insulin secretion (GSIS). However, chronic and persistent elevation of ROS, resulting from inflammation or excessive metabolic fuels such as glucose and fatty acids, may elevate antioxidant enzymes such that they blunt ROS and redox signalling, thus impairing ß-cell function. An interesting mitochondrial protein whose main function appears to be the control of ROS is uncoupling protein 2 (UCP2). Despite continuing investigation of the exact mechanism by which UCP2 is 'activated', it is clear that UCP2 levels and/or activity impact the efficacy of GSIS in pancreatic islets. This review will focus on the paradoxical roles of ROS in pancreatic ß-cell function and the regulatory role of UCP2 in ROS signalling and GSIS.

Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole: preemptive dose modification and therapeutic drug monitoring.

Concomitant use of tacrolimus and voriconazole, both competitive inhibitors of the CYP450 3A4 isoenzyme, requires tacrolimus dose reduction. On the basis of clinical observations, we developed a preemptive dose-reduction strategy in allograft recipients who received voriconazole to maintain tacrolimus concentrations within a target range. A total of 27 patients started i.v. tacrolimus at an average daily dose of 0.022 mg/kg on day -1 (30% lesser than the usual starting dose). The dose was reduced by 30-40% if the 48-h steady-state concentration was 7-10 ng/ml, and by 40-50% if it was 10-15 ng/ml. No change was made if the concentration was <7 ng/ml. Subsequently, concentrations were generally monitored 2-3 times a week with dose adjustments as necessary. None of the 170 levels (3-12 per patient; median 5) obtained between days +1 and +16 were subtherapeutic (<5 ng/ml) and only 34 levels (20%) were >15 ng/ml. Each patient required dose reduction at least twice. The dose had to be increased in only two patients after the initial dose reduction. The median tacrolimus doses in mg/kg declined with time; being 0.022, 0.008 and 0.006 on days 0, 7 and 14, respectively. We conclude that a preemptive dose-reduction strategy is effective in maintaining tacrolimus concentrations within the desired therapeutic range, although serial monitoring remains prudent.

On-line monitoring of pharmaceutical production processes using Hidden Markov Model.

This article presents a new method for on-line monitoring of pharmaceutical production process, especially the powder blending process. The new method consists of two parts: extracting features from the Near Infrared (NIR) spectroscopy signals and recognizing patterns from the features. Features are extracted from spectra by using Partial Least Squares method (PLS). The pattern recognition is done by using Hidden Markov Model (HMM). A series of experiments are conducted to evaluate the effectiveness of this new method. In the experiments, wheat powder and corn powder are blended together at a set concentration. The proposed method can effectively detect the blending uniformity (the success rate is 99.6%). In comparison to the conventional Moving Block of Standard Deviation (MBSD), the proposed method has a number of advantages, including higher reliability, higher robustness and more transparent decision making. It can be used for effective on-line monitoring of pharmaceutical production processes.

Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole.

Seventy-one allograft recipients receiving voriconazole, in whom complete clinical, microbiologic and pharmacokinetic data were available, were studied to determine the efficacy of voriconazole in preventing fungal infections. The length of voriconazole therapy was 6-956 days (median 133). The total number of patient-days on voriconazole was 13 805 ( approximately 38 years). A total of 10 fungal infections were seen in patients on voriconazole (18% actuarial probability at 1 year): Candida glabrata (n=5), Candida krusei (n=1), Cunninghamella (n=1), Rhizopus (n=2) and Mucor (n=1). Two of the four zygomycosis cases were preceded by short durations of voriconazole therapy, but prolonged itraconazole prophylaxis. The plasma steady-state trough voriconazole levels around the time the infection occurred were <0.2, <0.2, 0.33, 0.55, 0.63 and 1.78 microg/ml in the six candidiasis cases. Excluding the four zygomycosis cases, all the six candidiasis cases were seen among the 43 patients with voriconazole levels of < or =2 microg/ml and none among the 24 with levels of >2 microg/ml (P=0.061). We conclude that voriconazole is effective at preventing aspergillosis. However, breakthrough zygomycosis is seen in a small proportion of patients. The role of therapeutic voriconazole monitoring with dose adjustment to avoid breakthrough infections with fungi that are otherwise susceptible to the drug needs to be explored prospectively.

[Opinions of health professionals on the impact of the Preventive Activities and Health Promotion Program (PAPPS)]. / Opiniones de los profesionales sanitarios sobre la influencia del Programa de Actividades Preventivas y de Promoción de la Salud (PAPPS) en atención primaria.

OBJECTIVE: To find out the opinion of Primary Health Care (PHC) professionals on the impact of the Preventive Activities and Health Promotion Program (PAPPS). DESIGN: Descriptive qualitative-quantitative study. In a first phase the SWOT technique was used. In a second phase a 47 item questionnaire was designed using an ordinal scale. PARTICIPANTS: Professionals of PAPPS health centre, PAPPS managers and PHC management, using the Autonomous Community, and the time of ascribing or knowledge of PAPPS as segmentation criteria. In the qualitative study 62 participants were selected by theoretical sampling. In the quantitative study, 198 professionals took part in the survey. PRINCIPAL MEASUREMENTS: The assessment of the results has taken into account the responses to the questions formulated and by performing a crossed analysis between strengths/threats and weaknesses/opportunities. A descriptive statistical analysis of the questions in the questionnaire. RESULTS: There is agreement in that PAPPS has greatly influenced the development of PHC, contributing to improving the quality of care, but it is also fundamental to try revitalise the programme, as the limited involvement by the professionals in the postulated preventive recommendations is its main weakness, due to lack of motivation and professional burn-out.. CONCLUSIONS: According to the participants PAPPS has contributed significantly to the development of PHC in our country and has had an influence on professional practice by instilling a prevention culture that hardly existed before.

Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia.

Recombinant urate oxidase (rasburicase) lowers uric acid levels rapidly to very low levels at the labeled dose of 0.15-0.2 mg/kg daily for 5 days. Our past experience showed that a lower dose (3 mg) lowered uric acid levels sufficiently in most patients. A retrospective review was conducted to determine the effect of a fixed 3 mg dose of rasburicase in 43 adult patients with cancer undergoing hematopoietic stem cell transplantation or receiving chemotherapy who had elevated or rising uric acid levels (6.4-16.8 mg/dl; median 9.6). Six patients received a second dose of rasburicase (3 mg in four patients and 1.5 mg in two patients) 24 h later. Patients received allopurinol, adequate hydration, as well as other supportive therapy as required. Uric acid levels declined by 6-95% (median 43%) within the first 24 h after rasburicase administration, and levels at 48 h were 9-91% (median 65%) lower than the baseline levels. Serum creatinine changed by < or =10% in 21 patients, increased by >10% in four patients and decreased by >10% in 18 patients. No significant renal dysfunction developed in any of the patients. We conclude that rasburicase is effective in lowering uric acid levels at a fixed dose of 3 mg, which is much lower than the recommended dose.

Chronic UVA irradiation of human HaCaT keratinocytes induces malignant transformation associated with acquired apoptotic resistance.

Ultraviolet A (UVA, 315-400 nm), constituting about 95% of ultraviolet irradiation in natural sunlight, represents a major environmental challenge to the skin and is clearly associated with human skin cancer. It has proven difficult to show direct actions of UVA as a carcinogen in human cells. Here, we demonstrate that chronic UVA exposures at environmentally relevant doses in vitro can induce malignant transformation of human keratinocytes associated with acquired apoptotic resistance. As evidence of carcinogenic transformation, UVA-long-treated (24 J/cm(2) once/week for 18 weeks) HaCaT (ULTH) cells showed increased secretion of matrix metalloproteinase (MMP-9), overexpression of keratin 13, altered morphology and anchorage-independent growth. Malignant transformation was established by the production of aggressive squamous cell carcinomas after inoculation of ULTH cells into nude mice (NC(r)-nu). ULTH cells were resistant to apoptosis induced not only by UVA but also by UVB and arsenite, two other human skin carcinogens. ULTH cells also became resistant to apoptosis induced by etoposide, staurosporine and doxorubicin hydrochloride. Elevated phosphorylation of protein kinase B (PKB, also called AKT) and reduced expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) were detected in ULTH cells. The resistance of ULTH cells to UVA-induced apoptosis was reversed by either inhibition of phosphatidylinositol 3-kinase (PI-3K) or adenovirus expression of PTEN or dominant negative AKT. These data indicate that UVA has carcinogenic potential in human keratinocytes and that the increased AKT signaling and decreased PTEN expression may contribute to this malignant transformation. Further comparisons between the transformed ULTH and control cells should lead to a better understanding of the mechanism of UVA carcinogenesis and may help identify biomarkers for UVA-induced skin malignancies.

Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients.

Voriconazole, a new antifungal agent, is increasingly being used after HSCT. The hepatic cytochrome P450 isoenzyme 2C19 plays a significant role in voriconazole metabolism. As CYP2C19 exhibits significant genetic polymorphism, some patients metabolize voriconazole poorly resulting in increased plasma drug levels. The clinical significance of this is unknown, and the utility of monitoring voriconazole levels is unclear. Steady-state trough plasma voriconazole levels were obtained in 25 allogeneic HSCT recipients using an HPLC assay. Patients had drug levels checked once (n=13), twice (n=10), or > or =3 times (n=2) 5-18 days (median 10) after starting voriconazole or dose modification. The 41 voriconazole levels were 0.2-6.8 microg/ml (median 1.6); 6 (15%) were <0.5 (possibly below the in vitro MIC90 for Aspergillus spp.). Voriconazole concentrations correlated with aspartate aminotranferase (AST) (r=0.5; P=0.0009) and alkaline phosphatase (r=0.34; P=0.03), but not with creatinine, bilirubin and alanine aminotransferase (ALT). Since liver dysfunction is common after HSCT, it was not possible to determine if elevated AST and alkaline phosphatase levels were the cause or the consequence of higher voriconazole levels. We conclude that trough voriconazole levels vary considerably between patients, and suggest monitoring levels in patients receiving voriconazole for confirmed fungal infections, and in those with elevated AST or alkaline phosphatase levels.

Putative interhelical interactions within the PheP protein revealed by second-site suppressor analysis.

Highly conserved glycine residues within span I and span II of the phenylalanine and tyrosine transporter PheP were shown to be important for the function of the wild-type protein. Replacement by amino acids with increasing side chain volume led to progressive loss of transport activity. Second-site suppression studies performed with a number of the primary mutants revealed a tight packing arrangement between spans I and II that is important for function and an additional interaction between spans I and III. We also postulate that a third motif, GXXIG, present in span I and highly conserved within different members of the amino acid-polyamine-organocation family, may function as a dimerization motif. Surprisingly, other highly conserved residues, such as Y60 and L41, could be replaced by various residues with no apparent loss of activity.

[Evaluation of the utility and efficacy of a day hospital in a gastroenterology department]. / Valoración de la utilidad y eficacia de un hospital de día en un servicio de patología digestiva.

Because public health funds are limited, full advantage should be taken of the resources available. Consequently, hospital stay should be reduced with no loss of health care quality. In our Gastroenterology Department, investigations or treatment requiring a short hospital stay are carried out in a day hospital. Between March 1998 and March 2000, 2,169 patients were treated: 1,862 outpatients and 307 patients referred from another hospital. A total of 95.2% of the outpatients were discharged. Hospital stay was prolonged in 4.8% (91/1,862): 13 due to incomplete investigations, 29 because of worsening of their underlying disease before the procedure and 49 due to complications. The overall complication rate was 2.8% (62/2,169). Six complications developed after discharge; of these two appeared within 24 hours. After the opening of the day hospital, the mean hospital stay in the Gastroenterology Department was reduced from 9.05 days to 6.07 days (p = 0.001). In conclusion, the use of a day hospital in a gastroenterology department is useful, effective, safe and profitable.

Influence of bed preparation on the incorporation of autogenous bone grafts: a study in dogs.

To study the influence of bed preparation on the incorporation of autogenous bone grafts in mandibles, 6 dogs with 3 different types of receptor bed were used: cortical, perforated, and decorticated. After 45 and 90 days, the animals were sacrificed and block sections of grafted and adjacent bone were removed. The specimens were prepared and stained with hematoxylin and eosin and Masson's trichromic. The autogenous bone grafts were integrated with the receptor bed, mainly in the perforated and decorticated groups. The poorest results were found in the cortical group.