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Zhonghua Yi Xue Za Zhi Apr 2024To explore the efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy in patients with...
To explore the efficacy and safety of laparoscopic radical gastrectomy after neoadjuvant chemotherapy combined with immunotherapy and targeted therapy in patients with gastric cancer. A retrospective analysis of clinical and pathological data of 20 patients with locally advanced gastric cancer (clinical TNM stage T3-4aN+M0) admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 2021 to July 2023. All patients received 3 cycles of SOX (Oxaliplatin+S-1) regimen combined with immunotherapy (Trastuzumab) and targeted therapy (Apatinib) as neoadjuvant treatment followed by laparoscopic radical gastrectomy for gastric cancer. Surgical outcomes, postoperative pathological response, and postoperative recovery were observed. Quantitative data, except for age and operation time, were expressed using Median (range). Among the 20 patients, there were 18 males and 2 females, aged 41 to 73 years [(60.6±9.7) years]. All 20 patients underwent laparoscopic surgical treatment after neoadjuvant therapy, with one patient undergoing laparoscopic conversion to open total gastrectomy with partial transverse colon resection due to tumor invasion into the transverse mesocolon. Eight patients underwent totally laparoscopic radical gastrectomy, all with Billroth Ⅱ+Braun anastomosis at the distal stomach. Eleven patients underwent laparoscopic-assisted radical gastrectomy, among which total gastrectomy with Roux-en-Y anastomosis was performed in ten cases, and proximal gastrectomy with esophagogastrostomy overlap anastomosis was performed in one case. The mean operation time for the 20 patients was (165.0±34.1) minutes; intraoperative blood loss was 80 (20-100) ml; and the number of lymph nodes retrieved was 68 (21-89). Postoperative pathological TNM staging revealed stage T0N0M0 in six cases, stage Ⅰ in two cases, stage Ⅱ in three cases, and stage Ⅲ in nine cases. Six patients (30.0%) achieved pathological complete response, and nine patients (45.0%) achieved significant pathological response. The median postoperative time to flatus was 4 (1-5) days; oral intake resumed after 3 (2-5) days; and the median length of hospital stay was 13 (6-19) days. One patient developed colonic anastomotic leakage with intra-abdominal infection, and one patient developed duodenal stump leakage with intra-abdominal infection, both classified as Clavien-Dindo grade 3A complications, and improved after treatment and discharged. One patient developed gastric paresis, and two patients developed pleural effusion, classified as Clavien-Dindo grade 2 complications, and improved after treatment and discharged. There were no deaths within 30 days after discharge. Laparoscopic radical gastrectomy for gastric cancer after neoadjuvant treatment with the SOX regimen combined with immunotherapy and targeted therapy is safe and feasible, with satisfactory short-term efficacy. However, there is an increase in overall surgical risk and difficulty, and it is recommended to be performed in experienced gastric cancer centers.
Topics: Humans; Gastrectomy; Male; Female; Middle Aged; Neoadjuvant Therapy; Laparoscopy; Stomach Neoplasms; Retrospective Studies; Aged; Adult; Immunotherapy; Treatment Outcome
PubMed: 38644290
DOI: 10.3760/cma.j.cn112137-20230811-00206 -
Journal of the Formosan Medical... Apr 2024Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated...
BACKGROUND
Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated trend in Taiwan is unknown. Risk factors of DU recurrence have not been comprehensively investigated in children.
METHODS
This retrospective study included children diagnosed with DU to evaluate the demographics, symptoms, diagnostics, treatment, and outcomes. Specific populations (infant, surgery required) were sorted for subgroup analysis. Predictors of DU recurrence was analyzed in patients who received endoscopic follow-ups.
RESULTS
A total of 488 children were included. Most patients were male (72.5%), school-aged (11.3 ± 4.8 years old), and with varied underlying diseases in one-fifth. The annual incidences were around 3-5%, with a declining trend of case numbers and the Hp-positive proportion. Hp infection, concurrent gastric ulcer, perforation, and mortality were noted in 32.7%, 16%, 1.6%, and 1% of patients. Patients with or without Hp infection showed different clinical features but similar outcomes. The characteristics of subpopulations were depicted respectively. Male sex, lower Hb level, and perforation were independent risk factors associated with recurrence.
CONCLUSIONS
Hp-positive DU seems to wane. Patients with male sex, lower Hb level, or perforation at diagnosis carried a higher risk of recurrence, which may warrant active surveillance and endoscopic follow-up.
PubMed: 38644127
DOI: 10.1016/j.jfma.2024.04.011 -
American Journal of Surgery Apr 2024Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after...
BACKGROUND
Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after pancreas-preserving duodenectomy (PPrD) with potentially less morbidity.
METHODS
Retrospective cohort of all adult (age >18) patients who underwent PPrD with curative intent of a neoplasm in or invading into the duodenum at our institution from 2011 to 2022 (n = 29), excluding tumors involving the Ampulla of Vater or the pancreas. Statistical analyses were performed using STATA.
RESULTS
R0 resection was achieved in 93 % patients. Ten (34.4 %) experienced postoperative complications (13.7 % within Clavien-Dindo III-V). PPrD patients had lower rates of pancreatic leak, delayed gastric emptying, and deep surgical site infection.
CONCLUSIONS
In this case series, we demonstrate PPrD is safe and effective, with a high rate of complete resection and lower complication rate than that seen in pancreaticoduodenectomy.
PubMed: 38641448
DOI: 10.1016/j.amjsurg.2024.04.017 -
Journal of Pharmaceutical and... Aug 2024Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata...
Herb-drug interactions: Quantitative analysis of levofloxacin absorption and transporter expression in the rat intestine following combined treatment with Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross.
Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata extracts (PCE) have been used in combination with levofloxacin (LVFX) to treat urinary tract infections (UTIs) for a long time. However, little is known about the absorption of LVFX and transporter expression in the intestine after combined treatment with PCE, restricting the development and utilization of PCE. In view of this, a UPLC-MS/MS method was established for the determination of LVFX in intestinal sac fluid samples and in situ intestinal circulation perfusate samples to explore the effect of PCE on the intestinal absorption characteristics of LVFX ex vivo and in vivo. To further evaluate the interaction between LVFX and PCE, western blotting, immunohistochemistry, and RT-qPCR were utilized to determine the expression levels of drug transporters (OATP1A2, P-gp, BCRP, and MRP2) involved in the intestinal absorption of LVFX after combined treatment with PCE. Using the everted intestinal sac model, the absorption rate constant (K) and cumulative drug absorption (Q) of LVFX in each intestinal segment were significantly lower in groups treated with PCE than in the control group. K at 2 h decreased most in the colon segment (from 0.088 to 0.016 µg/h·cm), and Q at 2 h decreased most in the duodenum (from 213.29 to 33.92 µg). Using the intestinal circulation perfusion model, the K value and percentage absorption rate (A) of LVFX in the small intestine decreased significantly when PCE and LVFX were used in combination. These results showed that PCE had a strong inhibitory effect on the absorption of LVFX in the rat small intestine (ex vivo and in vivo intestinal segments). In addition, PCE increased the protein and mRNA expression levels of efflux transporters (P-gp, BCRP, and MRP2) and decreased the expression of the uptake transporter OATP1A2 significantly. The effects increased as the PCE concentration increased. These findings indicated that PCE changed the absorption characteristics of levofloxacin, possibly by affecting the expression of transporters in the small intestine. In addition to revealing a herb-drug interaction (HDI) between PCE and LVFX, these results provide a basis for further studies of their clinical efficacy and mechanism of action.
Topics: Animals; Levofloxacin; Intestinal Absorption; Rats; Herb-Drug Interactions; Rats, Sprague-Dawley; Male; Intestinal Mucosa; Drugs, Chinese Herbal; Tandem Mass Spectrometry; Plant Extracts; Membrane Transport Proteins; Anti-Bacterial Agents
PubMed: 38636190
DOI: 10.1016/j.jpba.2024.116156 -
Surgical Infections May 2024species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to...
species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204-14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934-29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044-1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968-0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features.
Topics: Humans; Male; Female; Risk Factors; Retrospective Studies; Middle Aged; Candidiasis, Invasive; Intraabdominal Infections; Critical Illness; Aged; Digestive System Surgical Procedures; Adult; Hospital Mortality; Aged, 80 and over
PubMed: 38634791
DOI: 10.1089/sur.2023.333 -
Redox Biology Jun 2024Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload...
Differentiation of intestinal stem cells toward goblet cells under systemic iron overload stress are associated with inhibition of Notch signaling pathway and ferroptosis.
Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h. We found that iron overload caused damage to intestinal morphology with a 64 % reduction in villus height/crypt depth ratio, and microvilli injury in the duodenum. Iron overload mediated epithelial function by inhibiting the expression of nutrient transporters and enhancing the expression of secretory factors in the duodenum. Meanwhile, iron overload inhibited the proliferation of ISCs and regulated their differentiation into secretory mature cells, such as goblet cells, through inhibiting Notch signaling pathway both in mice and enteroid. Furthermore, iron overload caused oxidative stress and ferroptosis in intestinal epithelial cells. In addition, ferroptosis could also inhibit Notch signaling pathway, and affected the proliferation and differentiation of ISCs. These findings reveal the regulatory role of iron overload on the proliferation and differentiation of ISCs, providing a new insight into the internal mechanism of iron overload affecting intestinal health, and offering important theoretical basis for the scientific application of iron nutrition regulation.
Topics: Animals; Ferroptosis; Mice; Goblet Cells; Iron Overload; Signal Transduction; Stem Cells; Cell Differentiation; Receptors, Notch; Oxidative Stress; Intestinal Mucosa; Cell Proliferation; Disease Models, Animal; Male
PubMed: 38631120
DOI: 10.1016/j.redox.2024.103160 -
Trials Apr 2024Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other...
BACKGROUND
Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).
METHODS/DESIGN
The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival.
DISCUSSION
The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care.
ETHICS AND DISSEMINATION
The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation.
TRIAL REGISTRATION
EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.
Topics: Adult; Humans; Adrenergic beta-Antagonists; Ascites; Carvedilol; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hypertension, Portal; Liver Cirrhosis; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 38627804
DOI: 10.1186/s13063-024-08063-3 -
Veterinaria Italiana Jul 2023This study aimed to investigate the comparison of effect of anticoccidal drugs including lasalocid and diclazuril with probiotic and synbiotic on the growth performance...
This study aimed to investigate the comparison of effect of anticoccidal drugs including lasalocid and diclazuril with probiotic and synbiotic on the growth performance and intestinal morphology in broiler chicken. One hundred eighty chickens (Ross 308, 1 day old) were randomly divided into 6 equal groups (n=30) including the negative control (basal diet), the positive control (basal diet+oral inoculation of 3×104 sporulated oocytes of E. tenella, and four treatment groups. At days of 28 and 49 of age, 9 chickens were blindly chosen from each group were scarified by decapitation and their various segments of small intestine including ileum, jejunum, and duodenum were evaluated histomorphologically. We found that the economic losses resulted from coccidial infection in the poultry industry are caused by the decreased performance of broiler chicken induced by morphological changes in the any three segments specially jejunum. The anticoccidial drugs, synbiotic and probiotic can partially prevent morphological changes in any three segments of small intestine in broiler chicken with coccidiosis. Since morphological changes in the jejunum begin earlier than in other parts and surface area of jejunal villi is important for nutrition absorbance as well as growth performance, lasolacid was found to a be more efficient treatment in this regard.
Topics: Animals; Lasalocid; Coccidiostats; Chickens; Probiotics; Intestine, Small; Poultry Diseases; Nitriles; Triazines
PubMed: 38625750
DOI: 10.12834/VetIt.2587.17307.2 -
Journal of Agricultural and Food... May 2024Phlorizin (PHZ) is one of the main pharmacologically active ingredients in . We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus...
Phlorizin (PHZ) is one of the main pharmacologically active ingredients in . We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially , is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3, CD4, and CD8 T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families , , and ). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including -006, , , , , and increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.
Topics: Animals; Gastrointestinal Microbiome; Mice; Cattle; Bacteria; Bovine Virus Diarrhea-Mucosal Disease; Diarrhea Viruses, Bovine Viral; Antiviral Agents; Feces; Female; Mice, Inbred BALB C; Male
PubMed: 38625103
DOI: 10.1021/acs.jafc.4c01228 -
Veterinary Immunology and... May 2024Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses worldwide in the swine industry. PEDV attacks the intestine, disrupts intestinal epithelium...
Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses worldwide in the swine industry. PEDV attacks the intestine, disrupts intestinal epithelium morphology and barrier integrity, and results in profound diarrhea and high mortality. A commercially available isotonic protein solution (IPS) (Tonisity Px) has anecdotally been reported to be effective in supportive treatment of piglets with active PEDV infections. This study evaluated the effects of supplementing (or not) the drinking water of 14 day old PEDV-infected piglets with the IPS on the content of E-cadherin, fibronectin, interferon-alpha (IFN-α), and matrix metalloproteinase 9 (MMP-9) in duodenal tissue. The content of PEDV DNA in feces was also measured. Though both groups had similar PEDV shedding at day 1, IPS piglets had significantly lower PEDV shedding at day 5, 14 and 21. The IPS group also had a shorter duration of PEDV virus shedding. Levels of E-cadherin and fibronectin, both of which are structural proteins in the intestine, remained unchanged from baseline in the IPS group, whereas the same molecules decreased significantly in the control group. IFN-α, an antiviral cytokine, and MMP-9, an enzyme that aids in tissue remodeling, were increased at days 5 and 14 post infection, and then decreased at day 21 post-infection in the IPS group compared to control. Overall, the IPS used in this study enhanced epithelial intercellular adhesion (E-cadherin) and extracellular matrix structure (fibronectin), resulted in significantand favorable changes in MMP-9 activity, and favorably modulated IFN-α production. This is the first report of this panel of biomarkers, especially MMP-9 and IFN-α, in the face of in vivo PEDV infection. This is also the first report to investigate a commercially available swine product that does not need to be administered in solid feed, and that is already registered for use throughout Asia, Europe, South America, and North America. Overall, the results of this study serve to clarify the behavior of 4 key biomarkers in the presence of in vivo PEDV infection. The results also indicate that IPS (Tonisity Px) supplementation is a viable intervention to modulate the porcine intestinal immune response with favorable effects on the intestine.
Topics: Animals; Swine; Virus Shedding; Porcine epidemic diarrhea virus; Coronavirus Infections; Swine Diseases; Fibronectins; Matrix Metalloproteinase 9; Cadherins; Intestines; Interferon-alpha; Cell Adhesion; Intestinal Mucosa
PubMed: 38608406
DOI: 10.1016/j.vetimm.2024.110753