In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
Acute myeloid leukaemia (AML) is one of the deadliest haematological malignancies. During pregnancy it is a rare comorbidity and can lead to adverse outcomes, such as death, without adequate treatment. The management of AML during pregnancy remains a challenge. We report the case of a primigravida 34-year-old, with 18 weeks of amenorrhoea, who attended the emergency department presenting with pain and hypertrophy of the oral mucosa, accompanied by intense asthenia. Acute myeloblastic leukaemia was diagnosed. The possibility of terminating the pregnancy was offered given the lack of evidence regarding the maternal-foetal outcome, but the patient rejected it, so chemotherapy treatment was started. In the ultrasound controls there was no evidence of teratogenic alterations nor foetal growth restriction, and there were no alterations in Doppler flow values. It was decided to end the pregnancy at 32 + 3 GW. A preterm male was born through eutocic delivery with a normal Apgar test and umbilical cord pH, and did not require resuscitation. The puerperium was favourable and 15 days following discharge she was admitted for a bone marrow transplant from her HLA identical sister. The patient died due to rejection of the transplant and the complications derived from this event. 相似文献
Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy. 相似文献
Purpose/aim: To focus on current aspects of primary thyroid lymphoma (PTL), which is a rare clinical entity usually manifested by a rapidly growing mass in the neck that can cause pressure symptoms.
Materials and Methods: Relevant papers in PubMed published through June 2017 were selected to track updated information about PTL with an emphasis on diagnosis and novel therapeutic management.
Results: The most frequent cases include non-Hodgkin lymphoma derived from B-cells, mainly diffuse large B-cell lymphoma (DLBCL) followed by mucosa-associated lymphoid tissue (MALT) lymphoma or a mixed type. Other subtypes are less common. Lymphomas derived from T-cells and Hodgkin lymphomas are extremely rare. Hashimoto's autoimmune thyroiditis has been implicated as a risk factor for lymphoma. At the molecular level, the Wnt5a protein and its receptor Ror2 are involved in the course of the disease. Ultrasonography, fine needle aspiration (FNA) biopsy, and core or open biopsy combined with new diagnostic facilities contribute to an accurate diagnosis. An increased potential exists for a cure without the need for a radical surgical procedure. Modern chemoradiation therapy plus the monoclonal antibody rituximab, which acts against CD20, have limited the need for surgical interventions and provide an excellent outcome in most cases. However, some cases have resulted in treatment failure or recurrence.
Conclusions: A multidisciplinary approach must be used to define the management policy in each case. Future efforts by researchers are likely to be focused on the molecular level. 相似文献
Summary We conducted a phase I clinical study of aziridinylbenzoquinone (Diaziquone, AZQ) given as a 4 hour infusion weekly × 4. Forty-five children with recurrent acute leukemia and 33 children with various advanced solid tumors participated. Severe myelosuppression was the dose limiting toxic effect, occurring in all patients at the upper dose levels. Gastrointestinal and hepatic toxicities were infrequent and not severe. No allergic reactions occurred. Objective tumor regression was noted in 3 of 25 patients with a CNS tumor and in 6 of 45 patients with acute leukemia. For phase II trials the recommended dosage of Diaziquone given by this schedule is 18 mg/M2×4 for patients with a solid tumor, and is 30 mg/M2/week × 4 for children with acute leukemia. 相似文献
Laparoscopic pancreatic surgery (LPS) has seen significant development but much of the knowledge refers to small and benign
pancreatic tumors. This study aims to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach
in patients with benign, premalignant, and overt malignant lesions of the pancreas. This study, currently, is the largest
single center experience worldwide. One hundred twenty-three consecutive patients underwent laparoscopic pancreatic surgery
from April 1998 to April 2007, 20 patients with cysts or pseudocysts for acute and chronic pancreatitis, laparoscopic pancreatic
drainage was performed, and were excluded from the analysis. The 103 patients were divided based on preoperative diagnosis:
group I, inflammatory tumors for chronic pancreatitis (eight patients); group II, cystic pancreatic neoplasms (29 patients);
group III, intraductal papillary mucinous neoplasms (10 patients); group IV, neuroendocrine pancreatic tumors (NETs) (43 patients);
and group V ductal adenocarcinoma (13 patients). The median tumor size was 5.3 cm. Pathologic data include R0 or R1 resection (transection margins on the specimen were inked). Perioperative data, postoperative complications, and resection
modalities were compared using statistical analysis. Long-term outcomes were analysed by tumor recurrence and patient survival.
The overall conversion rate was 7%. Laparoscopic distal pancreatic resection was performed in 82 patients (79.6%). Laparoscopic
spleen-preserving distal pancreatectomy (Lap SPDP) was performed in 52 patients (63.7%), but with splenic vessels preservation
in 22% and without splenic vessels preservation in 41.5%. Laparoscopic en-bloc splenopancreatectomy (Lap SxDP) was performed
in 30 patients (36.6%) and laparoscopic enucleation (Lap En) in 20 patients (19.4%). There was no mortality. The overall complication
rate was 25.2, 16.7, and 40% after Lap SPDP, Lap SxDP, and Lap En, respectively. The overall morbidity rate was significantly
higher (p > 0.05) in the group of Lap SPDP without splenic vessels preservation comparing with Lap SPDP with splenic vessels preservation
because of the occurrence of splenic complications (20.6%). The overall pancreatic fistulas was 7.7, 10, and 35% after Lap
SPDP, Lap SxDP, and Lap En, respectively; the severity of fistula was significantly higher in the Lap En group (p > 0.05). The mean hospital stay was within 1 week in all groups, except in the group of ductal adenocarcinoma, which is 8 days.
In this series, 27 patients (26.2%) had malignant disease. R0 resection was achieved in 90% of ductal adenocarcinoma and 100% for other malignant tumors. The median survival for ductal
adenocarcinoma patients was 14 months. This series demonstrates that LPS is feasible and safe in benign-appearing and malignant
lesions of the pancreas. 相似文献