Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis.

BACKGROUND: The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB). METHODS: This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi'an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model. RESULTS: Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes. CONCLUSIONS: We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Effects of light regime on the hatching performance, body development and serum biochemical indexes in Beijing You Chicken.

The paper aimed to study the effects of light regime during the incubation on hatching performance, body development and serum biochemical indexes in Beijing You Chicken (BYC). A total of 1,408 BYC eggs were randomly allocated into 4 groups: 24 h dark as the control (Inc24D); 3 light regimes were 8 h light and 16 h dark group (Inc8L:16D); 12 h light and 12 h dark group (Inc12L:12D); 16 h light and 8 h dark group (Inc16L:8D), respectively. There were 352 eggs in each group, 4 replicates each group and 1 tray each replicate, 88 eggs each tray. Light-emitting diode (LED) strips, white light with temperature of 4,500 to 5,000 K, 150 to 200 lx were set up. The results showed that light regimes had no significant effects on hatching rate of eggs, hatching rate of fertile eggs and healthy rate of chicks (P > 0.05), but the hatching rate of eggs was the lowest in the Inc24D group (87.22%), and the highest in the Inc12L:12D group (93.64%); Lighted incubation significantly affected the incidence of leg problems of 1-day-old chicks (P < 0.05). The incidence rate of leg problems was the highest in the Inc24D group (4.21%), and was decreased in Inc12L:12D and Inc16L:8D groups (P < 0.05). Femur length in the Inc12L:12D group was greater than that in the Inc24D and Inc16L:8D groups (P = 0.011), but there were no differences between Inc8L:16D group and other three groups (P > 0.05). The relative brain weight of 1-day-old chicks was higher in Inc24D and Inc16L:8D groups than in Inc8L:16D group (P = 0.052), but had no difference with Inc12L:12D group. Light regimes during incubation had no effects on serum total protein, albumen, globulin, and urea nitrogen content of 1-day-old chicks (P > 0.05), while the globulin content in Inc12L:12D group was numerically greater than in other three groups (P = 0.063). Lysozyme content in Inc12L:12D group was higher than that in the Inc24D and Inc8L:16D groups (P < 0.05), but had no difference with that in Inc16L:8D group. Light regime had no effect on serum total antioxidant capability (T-AOC) (P > 0.05), but significantly affected the activities of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) (P < 0.05). The GSH-Px and T-SOD activities in the Inc12L:12D group were higher than those in the Inc24D and Inc8L:16D groups. The MDA content of Inc24D was the highest (9.67 nmol/mL) compared to the others, which was very close to the significant level (P = 0.056). In conclusion, 12 h light and 12 h dark incubation has the potential to improve the hatching performance of BYC eggs, benefit for the long bone development, improve some serum immune and antioxidant indexes, and reduce the leg problems in 1-day-old chicks.

Effect of microRNA-409 on the pathogenesis of polycystic ovary syndrome.

OBJECTIVE: To explore the expression level of microRNA-409 in PCOS (polycystic ovary syndrome) rats, as well as its potential effects on fertility of PCOS rats and phenotypes of offspring rats. MATERIALS AND METHODS: PCOS model in rats was established by Letasazole administration. Follicular development of rats was evaluated by the percentages of the cystic follicle (FC) and corpus luteum (CL) of all follicles. The enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum levels of hormones in rats, including LH, LH/FSH, T, INS, FSH, and E2. Subsequently, PCOS rats received a subcapsular injection of microRNA-409 mimics. The expression level of microRNA-409 in ovary was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Serum levels of LH, LH/FSH, T, INS, FSH, and E2 in PCOS rats with microRNA-409 overexpression were accessed by enzyme-linked immunosorbent assay (ELISA) as well. PCOS rats were mated with male rats for recording pregnancy rate. At 6-week-old of offspring, they were sacrificed for detecting microRNA-409 level, percentages of FC and CL, as well as serum levels of hormones. RESULTS: PCOS rats showed irregular estrous cycle and they were mainly in the anestrum. Rats in the control group were in a regular estrous cycle. A higher percentage of FC and a lower percentage of CL were seen in PCOS rats compared with those of controls. ELISA data revealed higher serum levels of LH, LH/FSH, and T in PCOS rats compared with those of controls. However, levels of FSH and E2 were lower in PCOS rats. Although INS level increased in PCOS rats, we did not observe a significant difference in INS level between PCOS rats and control rats. MicroRNA-409 was lowly expressed in ovaries of PCOS rats than those of controls. After injection of microRNA-409 mimics into rat ovary, microRNA-409 expression remarkably upregulated than those PCOS rats without injection. Rats in PCOS+microRNA-409 mimics group showed the largest body weight compared with those in the PCOS group and control group. PCOS rats showed a lower pregnancy rate than those of controls, which was markedly increased after administration of microRNA-409 mimics. Rats in PCOS+microRNA-409 mimics group presented lower levels of LH, LH/FSH, T, and INS, but higher levels of FSH and E2 than those in PCOS group. CONCLUSIONS: MicroRNA-409 is lowly expressed in the ovary of PCOS rats. Overexpression of microRNA-409 could improve hormone levels and pregnancy rate in PCOS rats, as well as affect clinical phenotypes of their offspring.

[Expression and function of T-type α1H Ca(2)(+) channels in the rat model of Hirschsprung disease].

OBJECTIVE: To investigate the role of T-type α1H Ca(2+) channels(Cav 3.2) in the pathogenesis of Hirschsprung disease(HD). METHOD: Eighty neonatal SD rats 6 to 8 days of age were randomly divided into 2 groups, 40 in each. Microinjector catheters were carefully placed into the bowl of one group, and 0.2% benzalkonium chloride (BAC) solution was injected to establish HD rat model. Control group was treated with saline instead of benzalkonium chloride. At postoperative 4, 6 and 8 weeks, ten rats were sacrificed randomly and examined through general observation, histopathological observation and immunofluorescent staining of PGP 9.5 to identify the animal models. Meanwhile, the distribution of Cav 3.2 in abnormal colon of HD rat model was studied by immunohistochemical staining, Western blot, and the co-localization of Cav 3.2 and c-kit was studied by double immunofluorescent staining. Besides, function of Cav 3.2 was surveyed with the model rats tensile force and frequency of colonic muscle in vitro. RESULT: After 8 weeks of BAC treatment, the rat model was successfully established according to the results of histopathological and immunofluorescent staining, which showed decrease or lack of ganglion cells within the area of BAC treatment. The distribution of Cav 3.2 was detected by immunohistochemical staining. In the normal colon, Cav 3.2 were mainly distributed between circular muscle and longitudinal muscle, and showed continuous distribution. However, in the narrow segment of HD rat model, the distribution of Cav 3.2 was decreased significantly, and its continuity was destroyed . The results of Western blot were quite consistent with immunohistochemistry staining, in the narrow segment of HD rat model, the expression of Cav 3.2 was decreased gradually after the BAC treatment, especially at postoperative 8 weeks. The relative expression of Cav 3.2 of the control group was 0.63±0.06, 0.62±0.09, 0.63±0.06 at postoperative 4, 6 and 8 weeks respectively. While that of HD group was 0.63±0.06, 0.38±0.06, 0.26±0.07 respectively, which was significantly lower as compared with that of control group at postoperative 6 and 8 weeks respectively (t-value 5.27 and 8.63 respectively, both P<0.05). The co-localization of Cav 3.2 and c-kit was studied by double immunofluorescent staining. Similarly, compared with control groups, the co-localization of Cav 3.2 and c-kit were reduced obviously or vanished in the narrow segment of HD rat model. In motility studies, the control rats show cyclic depolarization regularly. However, the cyclic depolarization largely disappeared in model rats. Besides, on the premise of cyclic depolarization in control muscle strips, when we added ZnCl2, known to inhibit Cav 3.2 selectively among three T-channel isoforms, into tissue chambers, the pattern of muscle contractions appear similar to HD model rats. CONCLUSION: The abnormal alteration of Cav 3.2 probably mediate the functional change of interstitial cells of cajal in the HD, and finally induce the intestinal dysfunction of HD.

Efficacy of an opposite position aspiration on resolution of pneumothorax following CT-guided lung biopsy.

OBJECTIVE: To evaluate the efficacy of aspiration in an opposite position to deal with pneumothorax after CT-guided lung biopsy. METHODS: A retrospective study was developed involving 210 patients with pneumothorax who had undergone CT-guided percutaneous core biopsies from January 2012 to March 2014 for various pulmonary lesions. Asymptomatic patients with minimal pneumothorax were treated conservatively. Simple manual aspiration was performed for symptomatic patients with minimal pneumothorax and for all patients with moderate to large pneumothorax. An opposite position aspiration was performed when simple manual aspiration failed. The efficacy of simple manual aspiration and the opposite position aspiration was observed. RESULTS: Among 210 patients with pneumothorax, 128 (61.0%) asymptomatic patients with minimal pneumothorax were treated conservatively. The remaining 82 were treated with attempted simple manual aspiration. Out of these 82 patients, simple manual aspiration was successful in 58 (70.7%, 58/82) cases. The complete and partial regression rates were 17.2% (10/58) and 82.8% (48/58), respectively. In the other 24 patients (29.3%, 24/82), simple aspiration technique was ineffective. An opposite position (from prone to supine or vice versa) was applied, and a new biopsy puncture site was chosen for reaspiration. This procedure was successful in 22 patients but not in 2 patients who had to have a chest tube insertion. The complete and partial regression rates were 25.0% (6/24) and 66.7% (16/24), respectively. Applying the new method, the total effective rate of aspiration improved significantly from 70.7% (58/82) to 97.6% (80/82). CONCLUSION: The opposite position aspiration can be safe, effective and minimally invasive treatment for CT-guided lung biopsy-induced pneumothorax thus reducing the use of chest tube significantly. ADVANCES IN KNOWLEDGE: (1) Opposite position aspiration can elevate the success rate of aspiration significantly (from 70.7% to 97.6% in our study); (2) this procedure is a safe, effective and minimally invasive treatment for pneumothorax caused by biopsy; and (3) opposite position aspiration is a useful technique to reduce the use of chest tube, which has clinical significance.

African green monkey origin of the atypical cytopathic 'stealth virus' isolated from a patient with chronic fatigue syndrome.

BACKGROUND: A cytomegalovirus-like 'stealth virus' had previously been isolated from a patient with the chronic fatigue syndrome (CFS). OBJECTIVE: To determine the original derivation of this virus. STUDY DESIGN: DNA sequencing of cloned regions of the virus was performed and the sequences were compared using BLASTN and FASTA analyses against the entire GenBank database. Viral sequences were also used to design primers for the polymerase chain reaction (PCR). RESULTS: DNA and amino acid sequence comparisons showed that the stealth virus was more closely related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of either human or rhesus monkey origin or to any other sequenced herpesvirus. Similarity, but non-identity, between the stealth virus and SCMV, was confirmed using PCR. CONCLUSION: The findings implicate the African green monkey as the probable source of the virus isolated from this CFS patient.

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome.

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative. Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV. The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered. Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related "stealth" virus that is able to establish a clinically persistent human infection.