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Nature Communications May 2024Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains...
Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8 T cells (T) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8 T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8 T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44CD62LCD8 T cells. Enhancement of CD8 T cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8 T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8 T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8 T cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.
Topics: Glycolysis; Animals; CD8-Positive T-Lymphocytes; Humans; Cell Differentiation; Mice; Female; Breast Neoplasms; Microwaves; Immunologic Memory; Deoxyglucose; Cell Line, Tumor; Liver Neoplasms; Memory T Cells
PubMed: 38821965
DOI: 10.1038/s41467-024-49059-6 -
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue Apr 2024To explore the independent risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis, establish an early warning model, and verify the...
OBJECTIVE
To explore the independent risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis, establish an early warning model, and verify the predictive value of the model based on synthetic minority oversampling technique (SMOTE) algorithm.
METHODS
A retrospective case-control study was conducted. 566 patients with sepsis who were admitted to Jinan People's Hospital from October 2016 to October 2022 were enrolled. General information, underlying diseases, infection sites, initial cause, severity scores, blood and arterial blood gas analysis indicators at admission, treatment measures, complications, and prognosis indicators of patients were collected. The patients were grouped according to whether ARDS occurred during hospitalization, and the clinical data between the two groups were observed and compared. Univariate and binary multivariate Logistic regression analysis were used to select the independent risk factors of ARDS during hospitalization in septic patients, and regression equation was established to construct the early warning model. Simultaneously, the dataset was improved using the SMOTE algorithm to build an enhanced warning model. Receiver operator characteristic curve (ROC curve) was drawn to validate the prediction efficiency of the model.
RESULTS
566 patients with sepsis were included in the final analysis, of which 163 developed ARDS during hospitalization and 403 did not. Univariate analysis showed that there were statistically significant differences in age, body mass index (BMI), malignant tumor, blood transfusion history, pancreas and peripancreatic infection, gastrointestinal tract infection, pulmonary infection as the initial etiology, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, albumin (Alb), blood urea nitrogen (BUN), mechanical ventilation therapy, septic shock and length of intensive care unit (ICU) stay between the two groups. Binary multivariate Logistic regression analysis showed that age [odds ratio (OR) = 3.449, 95% confidence interval (95%CI) was 2.197-5.414, P = 0.000], pulmonary infection as the initial etiology (OR = 2.309, 95%CI was 1.427-3.737, P = 0.001), pancreas and peripancreatic infection (OR = 1.937, 95%CI was 1.236-3.035, P = 0.004), septic shock (OR = 3.381, 95%CI was 1.890-6.047, P = 0.000), SOFA score (OR = 9.311, 95%CI was 5.831-14.867, P = 0.000) were independent influencing factors of ARDS during hospitalization in septic patients. An early warning model was established based on the above risk factors: P = -4.558+1.238×age+0.837×pulmonary infection as the initial etiology+0.661×pancreas and peripancreatic infection+1.218×septic shock+2.231×SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) of the model for ARDS during hospitalization in septic patients was 0.882 (95%CI was 0.851-0.914) with sensitivity of 79.8% and specificity of 83.4%. The dataset was improved based on the SMOTE algorithm, and the early warning model was rebuilt: P = -3.279+1.288×age+0.763×pulmonary infection as the initial etiology+0.635×pancreas and peripancreatic infection+1.068×septic shock+2.201×SOFA score. ROC curve analysis showed that the AUC of the model for ARDS during hospitalization in septic patients was 0.890 (95%CI was 0.867-0.913) with sensitivity of 85.3% and specificity of 79.1%. This result further confirmed that the early warning model constructed by the independent risk factors mentioned above had high predictive performance.
CONCLUSIONS
Risk factors for the occurrence of ARDS during hospitalization in patients with sepsis include age, pulmonary infection as the initial etiology, pancreatic and peripancreatic infection, septic shock, and SOFA score. Clinically, the probability of ARDS in patients with sepsis can be assessed based on the warning model established using these risk factors, allowing for early intervention and improvement of prognosis.
Topics: Humans; Sepsis; Respiratory Distress Syndrome; Retrospective Studies; Case-Control Studies; Risk Factors; Algorithms; Prognosis; Logistic Models; ROC Curve; Female; Male; Hospitalization
PubMed: 38813628
DOI: 10.3760/cma.j.cn121430-20230925-00821 -
Nature Immunology Jun 2024Viral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity...
Viral infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal infection restricts systemic glucose availability, which promotes the antiviral type I interferon (IFN-I) response. Following viral infection, we find that IFNγ produced by γδ T cells stimulates pancreatic β cells to increase glucose-induced insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral infection.
Topics: Animals; Immunity, Innate; Interferon-gamma; Mice; Blood Glucose; Insulin-Secreting Cells; Mice, Inbred C57BL; Signal Transduction; Insulin; Mice, Knockout; Hyperglycemia; Interferon Regulatory Factor-3; NF-kappa B; Humans; Liver; Male
PubMed: 38811816
DOI: 10.1038/s41590-024-01848-3 -
Frontiers in Microbiology 2024() genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis...
() genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using comparative genome analysis, we identified one of the genes, Rv1509, as a signature protein exclusively present in . To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in () constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, and studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages. Ms_Rv1509 also promoted phagolysosomal escape inside macrophages to boost bacterial replication and dissemination. infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection. Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing toward the role of Rv1509 in pathogenesis.
PubMed: 38803374
DOI: 10.3389/fmicb.2024.1344857 -
The Annals of Pharmacotherapy May 2024Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV...
BACKGROUND
Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.
OBJECTIVE
The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.
METHODS
This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.
RESULTS
Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.
CONCLUSION AND RELEVANCE
Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.
PubMed: 38801191
DOI: 10.1177/10600280241255110 -
Cureus Apr 2024Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to... (Review)
Review
Type 1 diabetes mellitus is an autoimmune condition characterized by insulin deficiency resulting from loss of function of beta cells in the pancreas, leading to hyperglycemia and associated long-term systemic complications and even death. Immunotherapy demonstrates beta cell function-preserving potential; however, its impact on C-peptide levels, a definitive biomarker of beta cell function, and endogenous insulin secretion remain unclear. A systematic review of various immunotherapeutic interventions is hence needed for a comprehensive assessment of their effectiveness as well as identifying research gaps and influencing future research and clinical decisions. An extensive literature search was done in PubMed, Scopus, and Cochrane Library databases using precise keywords and filters to identify relevant studies. Three independent reviewers assessed eligibility according to predetermined eligibility criteria, and data was extracted. The Cochrane risk of bias assessment tool (RoB 2.0) was used to evaluate the quality and validity of the included studies. A senior reviewer resolved discrepancies and differences of opinion between independent reviewers. A total of 11 studies were included, with 1464 study participants. Both Phase II and III trials were included. Within the included studies, four studies assessed the anti-CD3 monoclonal antibody otelixizumab as an intervention. Another anti-CD3 monoclonal antibody, teplizumab, was assessed as an intervention in four studies, whereas two studies assessed the anti-CD20 antibody rituximab and one study assessed abatacept as its interventional drug. Otelixizumab demonstrated benefits at higher doses but was associated with adverse effects like Ebstein-Barr virus reactivation and cytomegalovirus infection, while at lower doses it failed to show a significant difference in C-peptide levels or glycosylated hemoglobin (HbA1c). Teplizumab, on the other hand, showed promise in reducing C-peptide loss and exogenous insulin requirements and was associated with adverse events such as rash, lymphopenia, urinary tract infection, and cytokine release syndrome. However, these reactions were only associated with therapy initiation, and they subsided on their own. Rituximab improved C-peptide responses, and abatacept therapy demonstrated reduced loss of C-peptide, improved C-peptide levels, and lowered HbA1c. Teplizumab, rituximab, otelixizumab, and abatacept show potential for preserving beta cell function by reducing C-peptide loss in patients with type I diabetes mellitus. However, careful monitoring of adverse reactions, particularly viral infections and cytokine release syndrome, is necessary for the safe implementation of these therapies.
PubMed: 38800168
DOI: 10.7759/cureus.58981 -
Journal of Medical Case Reports May 2024Wandering spleen is a rare clinical entity in which the spleen is hypermobile and migrate from its normal left hypochondriac position to any other abdominal or pelvic... (Review)
Review
BACKGROUND
Wandering spleen is a rare clinical entity in which the spleen is hypermobile and migrate from its normal left hypochondriac position to any other abdominal or pelvic position as a result of absent or abnormal laxity of the suspensory ligaments (Puranik in Gastroenterol Rep 5:241, 2015, Evangelos in Am J Case Rep. 21, 2020) which in turn is due to either congenital laxity or precipitated by trauma, pregnancy, or connective tissue disorder (Puranik in Gastroenterol Rep 5:241, 2015, Jawad in Cureus 15, 2023). It may be asymptomatic and accidentally discovered for imaging done for other reasons or cause symptoms as a result of torsion of its pedicle and infarction or compression on adjacent viscera on its new position. It needs to be surgically treated upon discovery either by splenopexy or splectomy based on whether the spleen is mobile or not.
CASE PRESENTATION
We present a case of 39 years old female Ethiopian patient who presented to us complaining constant lower abdominal pain especially on the right side associated with swelling of one year which got worse over the preceding few months of her presentation to our facility. She is primiparous with delivery by C/section and a known case of HIV infection on HAART. Physical examination revealed a right lower quadrant well defined, fairly mobile and slightly tender swelling. Hematologic investigations are unremarkable. Imaging with abdominopelvic U/S and CT-scan showed a predominantly cystic, hypo attenuating right sided pelvic mass with narrow elongated attachment to pancreatic tail and absent spleen in its normal position. CT also showed multiple different sized purely cystic lesions all over both kidneys and the pancreas compatible with AD polycystic kidney and pancreatic disease. With a diagnosis of wandering possibly infarcted spleen, she underwent laparotomy, the finding being a fully infarcted spleen located on the right half of the upper pelvis with twisted pedicle and dense adhesions to the adjacent distal ileum and colon. Release of adhesions and splenectomy was done. Her post-operative course was uneventful.
CONCLUSION
Wandering spleen is a rare clinical condition that needs to be included in the list of differential diagnosis in patients presenting with lower abdominal and pelvic masses. As we have learnt from our case, a high index of suspicion is required to detect it early and intervene by doing splenopexy and thereby avoiding splenectomy and its related complications.
Topics: Adult; Female; Humans; Abdominal Pain; Pelvic Pain; Spleen; Splenectomy; Tomography, X-Ray Computed; Wandering Spleen
PubMed: 38790071
DOI: 10.1186/s13256-024-04580-6 -
JPMA. the Journal of the Pakistan... May 2024Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity,... (Review)
Review
Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity, mortality and financial burden. The global prevalence of pancreatitis is substantial, with the highest rates observed in central and eastern Europe. Diagnosing acute pancreatitis involves considering clinical symptoms, elevated serum amylase and/or lipase levels, and characteristic imaging findings. The causes of acute pancreatitis include obstructive disorders, such as gallstones and biliary sludge, alcohol consumption, smoking, drug-induced pancreatitis, metabolic disorders, trauma, medical procedures, infections, vascular diseases and autoimmune pancreatitis. Appropriate management of acute pancreatitis involves determining the severity of the condition, providing supportive care, addressing the underlying cause, and preventing complications. Advances in classifying the severity of acute pancreatitis and implementing goal-directed therapy have contributed to a decrease in mortality rates. Understanding its prevalence, aetiology and management principles is crucial for clinicians to appropriately diagnose and manage patients with acute pancreatitis.
Topics: Humans; Pancreatitis; Acute Disease; Severity of Illness Index; Gallstones
PubMed: 38783446
DOI: 10.47391/JPMA.9280 -
Heliyon May 2024Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick...
BACKGROUND
Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide.
METHODS
Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue.
RESULTS
Autopsy tissue evaluation demonstrated in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by -induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia.
CONCLUSIONS
Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.
PubMed: 38779029
DOI: 10.1016/j.heliyon.2024.e31159 -
Zhonghua Wei Chang Wai Ke Za Zhi =... May 2024To assess the safety and feasibility of Bi's intestinal loop binding treatment of esophageal jejunal anastomotic leak after total gastrectomy. Bi's Intestinal loop...
To assess the safety and feasibility of Bi's intestinal loop binding treatment of esophageal jejunal anastomotic leak after total gastrectomy. Bi's Intestinal loop binding are suitable for patients who underwent radical total gastrectomy+Roux-en-Y anastomosis and were confirmed by upper gastrointestinal angiography to have esophageal jejunal anastomotic leakage and whose conservative or endoscopic treatment was ineffective. The operation procedure is as follows: take the original central incision of the upper abdomen, remove the abscess around the anastomoses after ventral incision, and place drainage tube inside the abscess, which is convenient to rinse and drain after operation. A double 1-0 VICRYL is applied to the loop of gastrointestinal surrogate 10-15 cm proximal to the jejuno-jejunal anastomosis. The knot tension is tight to prevent regurgitation of digestive juices, but too much force should be avoided to cut the intestinal tract. Nutritional jejunostomy fistula was performed at 10‒15 cm distal to the jejuno-jejunal anastomosis and gastric tube was retained during the operation. The preoperative and postoperative data from 12 patients with jejunal esophageal anastomotic leak after total radical gastrectomy and Roux-en-Y anastomosis were retrospectively analyzed from October 2016 to January 2023 in gastrointestinal surgery and pancreas surgery at Shanxi People's Hospital, and observed the curative effect. 12 patients were managed with Bi's Intestinal loop binding, operative time (60.0±20.8) minutes, median bleeding (50±10.8) ml, median hospital stay 20(12~28) days, and median reviewing upper and mid Gastrointestinal Contrast time postoperatively 61(52~74) days. The results showed that the anastomoses healed well, all the small intestine showed good imaging, the binding wire fell off by itself, and two patients had incision infection. It is safe and feasible for patients with esophageal jejunostomy fistulae after total gastrectomy to use the method of Bi's Intestinal loop binding.
Topics: Humans; Gastrectomy; Anastomotic Leak; Male; Jejunum; Female; Retrospective Studies; Middle Aged; Esophagus; Anastomosis, Roux-en-Y; Aged; Anastomosis, Surgical; Treatment Outcome
PubMed: 38778690
DOI: 10.3760/cma.j.cn441530-20230724-00011