Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

A preoperative risk model for early recurrence after radical resection may facilitate initial treatment decisions concerning the use of neoadjuvant therapy for patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy may benefit patients with pancreatic ductal adenocarcinoma with resectable and borderline disease. Inappropriate use of neoadjuvant therapy, however, may lead to the loss of therapeutic opportunities. Until an effective prediction model of individual drug sensitivity is established, no accurate model exists to help surgeons decide on the appropriate use of neoadjuvant chemotherapy. We hypothesized that early recurrence in patients undergoing upfront, early resection may be an indication for neoadjuvant chemotherapy. Therefore, we aimed to use preoperative clinical parameters to establish a model of early recurrence to select patients at high risk for neoadjuvant chemotherapy. METHODS: Patients who underwent resection for pancreatic ductal adenocarcinoma between January 2014 and November 2017 were analyzed retrospectively. After the minimum P-value approach, the patients were divided into three groups: early recurrence, middle recurrence, and late/non-recurrence. Preoperative clinicopathologic factors that could predict early recurrence were included in a Cox proportional hazards regression model for univariate and multivariate analyses. The factors related to early recurrence were included to establish nomogram and decision tree models, which were then validated in 68 patients. RESULTS: We found that 235 (72.5%) of 324 patients had recurrence with a median recurrence-free survival of 210 days. The early recurrence, middle recurrence, and late/non-recurrence groups differed in preoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels, "resectability" on cross-sectional imaging, resection requiring a vascular resection, T stage, tumor size, and adjuvant chemotherapy. The best cutoff value of early recurrence was the first 162 days postoperatively. Univariate and multivariate analyses showed that selected preoperative chief complaints, lymph node enlargement and resectability on cross-sectional imaging, preoperative carbohydrate antigen 19-9 levels >210 kU/L, and a neutrophil/lymphocyte ratio >4.2 were independent predictors for early recurrence. CONCLUSION: We have successfully built a prediction model of early recurrence of patients with pancreatic ductal adenocarcinoma with the optimal cutoff early-recurrence value of 162 days. Our nomogram and decision tree models may be used to select those at high risk for early recurrence to guide preoperative decision-making concerning the use of neoadjuvant therapy in those patients who have "resectable" disease and not only the more classic criteria of borderline resectability.

Metastatic infection caused by hypervirulent Klebsiella pneumonia and co-infection with Cryptococcus meningitis: A case report.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) used to affect mainly people with compromised immunity or weakened by other infections, but recent emergence of hypervirulent strains has increased infections even in healthy individuals. These infections include liver abscess, pneumonia, bacteremia, meningitis, necrotizing fasciitis, and endophthalmitis. Although metastatic infection by hypervirulent K. pneumoniae (hvKP) is increasingly recognized, co-infection with Cryptococcus neoformans (C. neoformans) meningitis in immunocompetent hosts is rare but fatal. So, it is necessary to determine the risk factors, complications, and comorbidity of this disease. CASE SUMMARY: This report describes a 58-year-old man with hvKP pulmonary abscess, bacteremia, and meningitis, accompanied by fatal Cryptococcus meningitis. This patient presented with fever for 1 wk and drowsiness for 3 d. Laboratory findings revealed pulmonary abscess and bacteremia of K. pneumoniae. He was given intravenous antibiotic therapy, and the infection was under control for about 1 wk. However, his condition deteriorated rapidly because of metastatic purulent meningitis. Although hvKP and C. neoformans were isolated and confirmed, the patient died of spontaneous respiratory and cardiac arrest caused by cerebral hernia. CONCLUSION: HvKP has emerged as a cause of metastatic infections in immunocompetent hosts. polymicrobial co-infections should be taken into consideration when metastatic infection is present.

Streptomyces xinjiangensis sp. nov., an actinomycete isolated from Lop Nur region.

A novel actinobacterial strain, designated LPA192(T), was isolated from a soil sample collected from Lop Nur, Xinjiang Uygur Autonomous Region, Northwest China. A polyphasic approach was used to investigate the taxonomic position of strain LPA192(T). The isolate showed morphological and chemotaxonomic characteristics typical of members of the genus Streptomyces. Peptidoglycan was found to contain LL-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H6) and MK-10(H4). Polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylinositol. Major cellular fatty acids consist of C16:0, anteiso-C15:0 and C18:1 ω9c. The sugar in whole-cell hydrolysates was mannose. Phylogenetic analysis indicated that strain LPA192(T) is closely related to Streptomyces tanashiensis LMG 20274(T) (99.3 %), Streptomyces gulbargensis DAS131(T) (99.3 %), Streptomyces nashvillensis NBRC 13064(T) (99.3 %), Streptomyces roseolus NBRC 12816(T) (99.2 %) and Streptomyces filamentosus NBRC 12767(T) (99.1 %) while showing below 98.5 % sequencing similarities with other validly published Streptomyces species. However, DNA-DNA relatedness values between LPA192(T) and the closely related type strains were below 40 %, which are much lower than 70 % threshold value for species delineation. The genomic DNA G + C content of strain LPA192(T) was 69.3 mol %. Based on the differences in genotypic and phenotypic characteristics from the closely related strains, strain LPA192(T) is considered to represent a novel species of the genus Streptomyces for which the name Streptomyces xinjiangensis sp. nov. is proposed. The type strain is LPA192(T) (=KCTC 39601(T) = CGMCC 4.7288(T)).

Saccharothrix lopnurensis sp. nov., a filamentous actinomycete isolated from sediment of Lop Nur.

A novel actinomycete strain, designated YIM LPA2h(T), was isolated from a sediment sample collected from Lop Nur, Xinjiang Uygur Autonomous Region, North-West China. The taxonomic position of strain YIM LPA2h(T) was investigated by a polyphasic approach. The morphological and chemotaxonomic properties of the isolate were in accordance with the members of the genus Saccharothrix. The 16S rRNA gene sequence of the strain showed highest similarities to Saccharothrix yanglingensis (98.6 %), Saccharothrix longispora (98.4 %) and Saccharothrix hoggarensis (98.3 %). However, the DNA-DNA hybridization values between the new isolate YIM LPA2h(T) and S. yanglingensis, S. longispora and S. hoggarensis were significantly below 70 %. Strain YIM LPA2h(T) was found to contain meso-diaminopimelic acid as diagnostic diamino acid. The major sugars in whole-cell hydrolysates were rhamnose, galactose, mannose, glucose and fructose. The major polar lipids were identified as phosphatidylethanolamine, phosphatidylhydroxylethanolamine, diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside. The predominant respiratory menaquinones were MK-9 (H4) and MK-10 (H4). The major fatty acids were C17:1 ω8c (15 %), iso-C15:0 (12 %), anteiso-C15:0 (12 %) and summed feature 3 (C16:1 ω6c/C16:1 ω7c, 10 %). The genomic DNA G+C content of strain YIM LPA2h(T) was determined to be 75 mol %. The genotypic and phenotypic results suggest that strain YIM LPA2h(T) represents a novel species of the genus Saccharothrix, for which the name Saccharothrix lopnurensis sp. nov. is proposed. The type strain is YIM LPA2h(T) (=CGMCC 4.7246(T)=KCTC 39545(T)).

[Upregulation of P2X3 receptors in dorsal root ganglion of TRPV1 knockout female mice].

The study was aimed to investigate the changes in mechanical pain threshold in the condition of chronic inflammatory pain after transient receptor potential vanilloid 1 (TRPV1) gene was knockout. Hind-paw intraplantar injection of complete freund's adjuvant (CFA, 20 µL) produced peripheral inflammation in wild-type and TRPV1 knockout female mice. The mechanical pain thresholds were measured during the 8 days after injection and pre-injection by using Von-Frey hair. Nine days after injection, mice were killed and the differences of expression of c-Fos and P2X3 receptor in the dorsal root ganglia (DRG) and spinal cord dorsal horn were examined by Western blotting between the two groups. Compared with that in wild-type mice, the mechanical pain threshold was increased significantly in TRPV1 knockout mice (P < 0.05); 3 days after CFA injection, the baseline mechanical pain threshold in the TRPV1 knockout mice group was significantly higher than that in the wild-type mice group (P < 0.05); The result of Western blotting showed that the expression of c-Fos protein both in DRG and spinal cord dorsal horn of TRPV1 knockout mice group was decreased significantly compared with that in wild-type mice group (P < 0.01, P < 0.05), while the expression of P2X3 receptor in DRG of TRPV1 knockout mice group was increased significantly compared with that in wild-type mice group (P < 0.05). Our findings indicate that TRPV1 may influence the peripheral mechanical pain threshold by mediating the expression of c-Fos protein both in DRG and spinal cord dorsal horn and changing the expression of P2X3 receptor in DRG.