-
In Vivo (Athens, Greece) 2024Neoadjuvant radiochemotherapy followed by surgery is a standard of care in locally advanced rectal cancer (LARC). Only a subgroup of patients can obtain a pathological...
BACKGROUND/AIM
Neoadjuvant radiochemotherapy followed by surgery is a standard of care in locally advanced rectal cancer (LARC). Only a subgroup of patients can obtain a pathological complete response (pCR) and achieve good local control. However, the role of pCR on patient survival is debated. The aim of the study was to evaluate the impact of pCR on clinical outcomes and toxicities in LARC patients treated with dose intensification and concomitant capecitabine treatment in a neoadjuvant radiochemotherapy schedule.
PATIENTS AND METHODS
This was a single Institution retrospective study including 178 patients. Mandard tumor regression grade (TRG) and pTNM staging system were used to classify pathological response and define pathological complete response (pCR). Patients were divided in: pCR (pT0N0) and Not-pCR (pT>0N>0), according to pTNM and in good responders (TRG1-2) and partial/not responders (TRG3-5), according to Mandard TRG. The Kaplan-Meier method was used to estimate OS, CSS, DFS and LC.
RESULTS
A low severe toxicity rate was observed. Acute Grade 3 lower bowel toxicity and Grade 3 cutaneous toxicity were reported in 2 (1.1%) patients, respectively. Late Grade >3 lower bowel toxicity was reported in 6 patients (3%) and late Grade >3 cutaneous toxicity was registered in one patient. No other severe acute and late toxicities were reported. The 5- and 10-year OS, CSS, DFS and LC rates were 85% and 75%, 94% and 92%, 83% and 81%, 88% and 88%, respectively. We observed a pCR rate of 36% and a good responders rate of 62%, in our study population. Both groups showed better rates for each analyzed clinical outcome.
CONCLUSION
Neoadjuvant radiochemotherapy with dose intensification in LARC patients resulted in favorable long-term oncological outcomes, pCR rate showed an optimal impact on OS and DFS with an acceptable toxicity.
Topics: Humans; Rectal Neoplasms; Male; Female; Neoadjuvant Therapy; Middle Aged; Aged; Adult; Treatment Outcome; Neoplasm Staging; Chemoradiotherapy; Aged, 80 and over; Retrospective Studies; Capecitabine; Kaplan-Meier Estimate
PubMed: 38688610
DOI: 10.21873/invivo.13577 -
Journal of Veterinary Internal Medicine 2024Hypothermia is a cause of neonatal calf death in cold climates. Practical and effective rewarming methods are important for bovine health within affected regions. (Comparative Study)
Comparative Study
BACKGROUND
Hypothermia is a cause of neonatal calf death in cold climates. Practical and effective rewarming methods are important for bovine health within affected regions.
HYPOTHESIS/OBJECTIVES
To compare the rewarming rate and blood analytes (glucose, lactate, and cortisol) of calves resuscitated with forced air with warm water bath, with or without oral administration of caffeine.
ANIMALS
Twenty healthy neonatal Holstein bull calves.
METHODS
In this randomized, prospective study, calves born healthy and without history of dystocia were cooled to 32°C rectal temperature then thermally resuscitated using either forced air rewarming or warm water bath (40°C) with or without oral administration of caffeine. Rectal temperatures were used to quantify recovery rate. Measurements of glucose, lactate, and cortisol were recorded for every 2°C change in rectal temperature.
RESULTS
Rectal temperature decline (0.03°C per minute) and total cooling time (191.0 ± 33.3 minutes) did not significantly differ among treatment groups. Calves were successfully resuscitated to 38°C by either method. Time required to euthermia using warm water was significantly faster (0.1°C per minute; 64.3 ± 17.8 minute; P < .05) than forced air (0.05°C per minute; 123.1 ± 20.0 minutes). Caffeine had no significant effect on resuscitation rate (P = .14; 95% CI, -0.002 to 0.024) in either treatment; however, caffeine was associated with reduced time to euthermia by 8.3 and 10.8 minutes, respectively. Changes in metabolic variables (glucose, lactate, and cortisol), were inversely related to rectal temperature with no statistical significance among rewarming methods.
CONCLUSIONS AND CLINICAL IMPORTANCE
Although warm water submersion is faster, forced air rewarming is an effective alternative for restoration of euthermia.
Topics: Animals; Cattle; Hypothermia; Animals, Newborn; Caffeine; Male; Cattle Diseases; Prospective Studies; Rewarming; Resuscitation; Hydrocortisone; Administration, Oral; Baths; Blood Glucose; Lactic Acid; Body Temperature; Random Allocation
PubMed: 38685595
DOI: 10.1111/jvim.17066 -
American Journal of Veterinary Research May 2024To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta...
Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.
OBJECTIVE
To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana).
ANIMALS
15 African elephants (6 males and 9 females) of various ages.
METHODS
Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling.
RESULTS
Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 μg·h/mL), maximum observed concentration (Cmax; 3.73 μg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 μg·h/mL; Cmax, 2.52 μg/mL; and absorption t1/2, 0.13 hours.
CONCLUSIONS
Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration.
CLINICAL RELEVANCE
African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.
PubMed: 38684186
DOI: 10.2460/ajvr.24.02.0039 -
Vaccines Apr 2024() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to...
() infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for , undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as () in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against . The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options-twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising vaccine candidate. In addition, this project demonstrates the suitability of the pre-exposed outbred pig model for vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of vaccine candidates into clinical trials.
PubMed: 38675805
DOI: 10.3390/vaccines12040423 -
Poultry Science Jun 2024The broiler industry is adversely affected by the rise in global temperature. This study investigated the effects of in ovo feeding of α-ketoglutaric acid (AKG) on...
In ovo feeding of α-ketoglutaric acid improves hepatic antioxidant-gene expression, plasma antioxidant activities and decreases body temperature without affecting broiler body weight under cyclic heat stress.
The broiler industry is adversely affected by the rise in global temperature. This study investigated the effects of in ovo feeding of α-ketoglutaric acid (AKG) on growth performance, organ weight, plasma metabolite, plasma oxidative stress, rectal temperature (RT), and hepatic mRNA expression of antioxidant-related genes in Arbor Acres broilers subjected to cyclic heat stress (HS). Three hundred fifty fertile eggs during incubation were divided into 5 groups according to AKG concentrations and temperature conditions. After dissolving AKG in distilled water at 0, 0.5, 1.0, and 1.5, 0% AKG was in ovo administered to 2 of the 5 groups whereas the remaining 3 groups received 0.5, 1.0, and 1.5%, respectively. From d 29 to 34 of age, 4 groups of birds received heat stress (HS) at 31°C ± 1°C for 6 h per day while the other group was kept at room temperature (21°C ± 1°C; NT). So, the 5 treatment groups were: 1) 0AKG-NT, where chicks hatched from eggs receiving 0% AKG were reared under thermoneutral conditions. 2) 0AKG-HS, where chicks hatched from eggs receiving 0% AKG were reared under cyclic HS conditions. 3) 0.5AKG-HS, where chicks hatched from eggs receiving 0.5% AKG were reared under cyclic HS conditions. 4) 1.0AKG-HS, where chicks hatched from eggs receiving 1.0% AKG were reared under cyclic HS conditions. 5) 1.5AKG-HS, where chicks hatched from eggs receiving 1.5% AKG were reared under cyclic HS conditions. HS significantly reduced body weight change (ΔBW %) and average daily gain (ADG) without affecting average daily feed intake (ADFI). Feed conversion ratio (FCR) was significantly increased (P = 0.003) in all HS-treated groups. A significant linear decrease in the final RT (P = 0.005) and a change in RT (P = 0.003) were detected with increasing AKG concentration. Total antioxidant capacity (P = 0.029) and antioxidant balance (P = 0.001) in plasma increased linearly with increasing AKG concentration whereas malondialdehyde concentrations were linearly decreased (P = 0.001). Hepatic gene expression of CAT (P = 0.026) and GPX1 (P = 0.001) were dose-dependently upregulated while nicotinamide adenine dinucleotide phosphate oxidase (NOX)1, NOX4, and heat shock protein (HSP)70 were linearly downregulated (P < 0.05). Hence, in ovo injection of AKG was effective in mitigating HS-induced oxidative stress without attenuating the adverse effects on broiler growth.
Topics: Animals; Chickens; Antioxidants; Liver; Ketoglutaric Acids; Body Temperature; Hot Temperature; Body Weight; Gene Expression; Ovum; Male; Dose-Response Relationship, Drug; Random Allocation
PubMed: 38670054
DOI: 10.1016/j.psj.2024.103749 -
Animal Bioscience Apr 2024This study aimed to determine the effects of increasing energy and protein levels in diets by including protected fat (PF), glycerol (GL), and soybean meal (SBM) on...
Dietary effects of protected fat, glycerol, and soybean meal on performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions.
OBJECTIVE
This study aimed to determine the effects of increasing energy and protein levels in diets by including protected fat (PF), glycerol (GL), and soybean meal (SBM) on growth performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions.
METHODS
Thirty-six steers (initial BW, 724.9 ± 58.3 kg; age, 25.5 ± 0.4 month) were assigned into Control (TDN 76%, CP 15%), PF (TDN 83.6%, CP 15%), PF+GL (TDN 83.6%, CP 15%) and PF+GL+SBM (TDN 83.6%, CP 16.5%) by randomized complete block design for a total of 16 weeks with division of 4 week periods. The average temperature-humidity index was 87.0 (1st period; Severe), 82.8 (2nd; Moderate), 71.4 (3rd; Comfort), and 68.1 (4th; Comfort).
RESULTS
The DMI showed no treatments differences during the whole experiment. However, DMI in 1st and 2nd period decreased by approximately 30% and 10% compared to 4th period, respectively. Higher ADG and FCR were noted for treatments compared to Control at both 1st and 2nd period (p<0.05). There were no treatment effects on rectal temperature (RT), cortisol, and behaviors during the entire experiment. However, both RT and cortisol in 0, 1st and 2nd period were higher than those of 3rd and 4th period (p<0.05). Carcass yield and grade remained unaffected by increasing TDN and CP levels. Behavioral changes in the hot season (1st period) included reduced lying (43%), increased standing (48%), decreased walking (62%), and decreased eating (38%) (p<0.05), with an increase in drinking by 54%. Rumination during standing was 53% higher, while rumination during lying was about 33% lower compared to the post-hot season (3rd period) (p<0.05).
CONCLUSION
Dietary supplementation of protected fat in late-fattening Hanwoo steers under heat stress had a positive effect on preventing a reduction in performance.
PubMed: 38665089
DOI: 10.5713/ab.23.0503 -
International Journal of Surgery Case... May 2024Obturator hernia accounts for less than 1 % of all documented cases of pelvic hernias. It most commonly presents as an obstructive syndrome in elderly, multiparous,...
INTRODUCTION AND IMPORTANCE
Obturator hernia accounts for less than 1 % of all documented cases of pelvic hernias. It most commonly presents as an obstructive syndrome in elderly, multiparous, slim women, characterized by a wider pelvis that facilitates the passage of the hernia sac through the obturator foramen alongside the obturator nerve. In this case, adhering to the SCARE (Updating Consensus Surgical CAse REport) checklist criteria, we present a typical scenario involving an elderly woman who was initially misdiagnosed with a fecaloma, concealing an obturator hernia.
CASE REPORT
An 85-year-old patient, displaying prodromal signs of senile disease, presented for medical attention with incapacitating abdominal pain in the right iliac fossa, accompanied by nausea and vomiting. Rectal examination revealed the presence of a fecaloma, and glycerin administration was performed rectally. The patient's condition worsened with the development of mental confusion and hyperactive delirium. Abdominal Computer tomography scan (CT scan) revealed right obturator hernia with enteral segment insinuation and dilation of the proximal bowel. An infraumbilical laparotomy was performed. The herniation of an ileal segment and the right ovary through the obturator foramen was identified. The content proved irreducible to manual maneuvers, leading to obturator muscle section following the dissection of the Retzius space. The right round ligament of the uterus was sectioned, and we manage to preserve the Obturatory branch of the lumbar plexus throughout dissection. A polypropylene mesh was positioned and secured with non-absorbable sutures on the Cooper's ligament, iliac crest, and obturator muscle and segmental enterectomy with primary anastomosis using a linear stapler was performed.
CLINICAL DISCUSSION
This demanding case brings to the spotlight the importance of reevaluating even the usual cases. We provide our experience bringing together an unusual diagnosis after the conduction of a once diagnosed fecaloma that almost went down to a perforated acute abdomen. Hence the importance of suspect obturator hernia in unknown obstructive abdomen in elderly women.
CONCLUSION
With this report we aim to raise awareness of careful propaedeutic inquiry of acute abdomen. We provide our experience bringing together the diagnosis that agrees with our literature review. Elderly patients commonly challenge the clinical evaluation, especially those with signs of senile disease. Thereby, inkling hidden diagnosis in typical scenarios can improve the patient's care in emergency settings.
PubMed: 38663288
DOI: 10.1016/j.ijscr.2024.109643 -
BMJ Open Apr 2024Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the...
INTRODUCTION
Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants.
METHODS AND ANALYSIS
This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation.
ETHICS AND DISSEMINATION
This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ChiCTR2300079199.
Topics: Female; Humans; Infant, Newborn; Male; China; Double-Blind Method; Enema; Enterocolitis, Necrotizing; Glycerol; Infant, Premature; Intensive Care Units, Neonatal; Meconium; Randomized Controlled Trials as Topic
PubMed: 38658011
DOI: 10.1136/bmjopen-2024-084704 -
World Journal of Urology Apr 2024To prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection using povidone-iodine (PI) and antibiotic prophylaxis (AP).
OBJECTIVE
To summarize available data and compare the efficacy of rectal disinfection using PI with non-PI methods prior to TRUS-PB.
EVIDENCE ACQUISITION
Three databases were queried through November 2023 for randomized controlled trials (RCTs) analyzing patients who underwent TRUS-PB. We compared the effectiveness of rectal disinfection between PI groups and non-PI groups with or without AP. The primary outcomes of interest were the rates of overall infectious complications, fever, and sepsis. Subgroups analyses were conducted to assess the differential outcomes in patients using fluoroquinolone groups compared to those using other antibiotics groups.
EVIDENCE SYNTHESIS
We included ten RCTs in the meta-analyses. The overall rates of infectious complications were significantly lower when rectal disinfection with PI was performed (RR 0.56, 95% CI 0.42-0.74, p < 0.001). Compared to AP monotherapy, the combination of AP and PI was associated with significantly lower risk of infectious complications (RR 0.54, 95% CI 0.40-0.73, p < 0.001) and fever (RR 0.47, 95% CI 0.30-0.75, p = 0.001), but not with sepsis (RR 0.49, 95% CI 0.23-1.04, p = 0.06). The use of fluoroquinolone antibiotics was associated with a lower risk of infectious complications and fever compared to non-FQ antibiotics.
CONCLUSION
Rectal disinfection with PI significantly reduces the rates of infectious complications and fever in patients undergoing TRUS-PB. However, this approach does not show a significant impact on reducing the rate of sepsis following the procedure.
Topics: Humans; Male; Anti-Infective Agents, Local; Antibiotic Prophylaxis; Disinfection; Image-Guided Biopsy; Povidone-Iodine; Prostate; Prostatic Neoplasms; Rectum
PubMed: 38652324
DOI: 10.1007/s00345-024-04941-2 -
JDS Communications May 2024Lipopolysaccharide (LPS) challenges are commonly used in animal studies as a model for infection with gram-negative bacteria and innate immune activation. We used a...
Lipopolysaccharide (LPS) challenges are commonly used in animal studies as a model for infection with gram-negative bacteria and innate immune activation. We used a low-dose LPS challenge for evaluating interindividual variation in innate immune responses in calves. This was part of a larger study aimed at predicting interindividual variation in feed efficiency in veal calves by variation in feeding motivation, digestion, metabolism, immunology, and behavioral traits. However, due to unexpected high mortality, this LPS challenge was performed in 32 calves rather than in 130 calves, which was initially intended in that larger study, and the 32 calves subjected to the LPS challenge were removed from that larger study. The objective of this short communication is to report the effects of a low-dose LPS challenge in those 32 calves and to examine whether the high variation in calves' responses to LPS could be explained by parameters related to feeding motivation, digestion, behavior, and immunology measured in early life. Thirty-two male Holstein-Friesian calves of Dutch origin were intravenously injected with LPS (0.05 μg/kg of body weight) at an age of 72 ± 0.6 d. Rectal temperature and respiratory frequency were recorded before injection and every hour after injection up to 6 h. In the 8 wk before the LPS challenge, measurements were performed related to general health, feeding motivation, digestion, behavior, and immunity. Following LPS administration, 3 calves died of shock, a fourth calf was euthanized because of severe symptoms of shock and 3 other calves were treated with corticosteroids to counteract observed symptoms of shock. Within the group of 25 relatively mild-responding calves, large interindividual variation in clinical responses to LPS was observed. The maximum increase in rectal temperature varied from 0.6 to 1.9°C and averaged 1.2 ± 0.39°C (coefficient of variation was 32%). The maximum increase in respiratory frequency varied from 16 to 132 bouts/min and averaged 60 ± 28 bouts/min (coefficient of variation was 48%). Little differences were found in early-life measurements between the 7 heavy and 25 mild responders, although heavy responders tended to have a better umbilical hernia score, and had a lower score in a human approach test (i.e., were less reactive) and lower presence of fecal pathogens. The maximum increase in rectal temperature correlated negatively with blood hemoglobin concentration at arrival of the calves at the facilities (r = -0.59) and in wk 4 (r = -0.53). The maximum increase in respiratory frequency correlated negatively with fecal color score (r = -0.43) and positively with fur score in wk 5 (r = 0.50). Overall, mortality (12.5%) and variation in clinical response was high after a low-dose LPS challenge in clinically healthy calves and some hematological and health measurements in early life were related to the clinical response of calves to LPS.
PubMed: 38646583
DOI: 10.3168/jdsc.2023-0437