Search

Background: Surgical futility has been defined as death within 72 h of emergency laparotomy. It is associated with patient distress, moral injury and opportunity costs. This study aimed to determine the rates of surgical futility after emergency laparotomy at a single high-volume centre, and to attribute costs to cases of surgical futility., Methods: A retrospective cohort study was conducted between 1st August 2021 and 1st August 2023 at a single high-volume acute hospital trust in the United Kingdom. A national patient-level costings system was used to determine the costs of hospital care from the day of surgery to the time of death., Results: In a cohort of 741 patients, there was a 3.6 % surgical futility rate. Most of these patients died within 24 h of surgery. The median total cost of admission for each patient was £14,118 (range £6,618 to £29,583). The median cost per day of admission was £6,004 (range £1,324 to £15,255)., Conclusion: This is the first study to report the costs of surgical futility in the emergency laparotomy setting. Futile surgery appears to cost more and require more resource than non-futile laparotomies. Further research should focus on how to better predict surgical futility, reduce inappropriate interventions and improve patient care., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Candice Downey reports financial support was provided by National Institute for Health and Care Excellence. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors. Published by Elsevier Ltd.) more...

Purpose: Emergency laparotomy is associated with high morbidity for the surgical patient. Understanding patients' health-related quality of life after their surgery is important to enhance the informed consent process, and to enable the evaluation and improvement of surgical care. This review aims to summarise the use of health-related quality of life tools in clinical trials involving patients undergoing emergency laparotomy., Methods: A systematic review was undertaken of the scientific literature published in the MEDLINE ® and PubMed databases between January 2011 and July 2021. A narrative synthesis approach was chosen to synthesise the diverse range of studies in a structured manner. All included papers were evaluated using the Cochrane Collaboration's tool for assessing risk of bias., Results: Eleven studies were selected for inclusion. Most of the studies had a low risk of bias. Two of the studies used health-related quality of life as the primary outcome measure. A variety of health-related quality of life measurement tools were used; the EQ-5D tool was the most popular questionnaire. Protocol adherence was dependent on the length of time which had elapsed after emergency surgery., Conclusion: There are many perceived challenges to collecting health-related quality of life data in the emergency surgery setting. Many of these can be offset with progressive trial designs. There is a need for further research in the systematic development of patient-reported outcomes for use in emergency surgery., (© 2023. The Author(s).) more...

Purpose: Levator ani muscle (LAM) avulsion affects up to 35% of women. Unlike obstetric anal sphincter injury, LAM avulsion is not diagnosed immediately after vaginal delivery, however, has a profound impact on quality of life. The management of pelvic floor disorders is in growing demand yet the significance of LAM avulsion in the context of pelvic floor dysfunction (PFD) is poorly understood. This study collates information on success of treatment for LAM avulsion to establish the best options for management of women., Methods: MEDLINE ® , MEDLINE ® In-Process, EMBASE, PubMed, CINAHL and The Cochrane Library were searched for articles that evaluated the management techniques used to treat LAM avulsion. The protocol was registered with PROSPERO (CRD42021206427)., Results: Natural healing of LAM avulsion occurs in 50% of women. Conservative measures, including pelvic floor exercises and pessary use are poorly studied. Pelvic floor muscle training for major LAM avulsions was of no benefit. Post-partum pessary use was only of benefit in the first three months for women. Surgeries for LAM avulsion are poorly researched but studies suggest they may provide benefit for 76-97% of patients., Conclusions: Whilst some women with PFD secondary to LAM avulsion improve spontaneously, 50% continue to have pelvic floor symptoms 1 year following delivery. These symptoms result in a significant negative impact on quality of life, however, it is not clear whether conservative or surgical methods are helpful. There is a pressing need for research to find effective treatments and explore appropriate surgical repair techniques for women with LAM avulsion., (© 2023. Crown.) more...

Background: Postoperative complications are common, but there are limited data regarding their implications on patients' quality of life. This study aimed to address this gap in the literature by analysing the impact of postoperative complications on patients' health-related quality of life., Methods: Data from the Perioperative Quality Improvement Programme were analysed, and included patient-level data for 19 685 adults who underwent elective major abdominal procedures in England since 2016. Postoperative complications were graded using the Clavien-Dindo classification. Quality of life was assessed by responses to the EuroQol five-dimension five-levels-of-response (EQ-5D-5L™) questionnaire before surgery, and at 6 and 12 months after operation. Ordinal logistic regression was used to estimate the association between Clavien-Dindo grades and quality of life. Tobit and ordinary least squares regression analyses were used to estimate the quality-adjusted life-year (QALY) loss resulting from postoperative complications between admission and 12 months after surgery., Results: At 6 and 12 months after surgery, increasingly severe postoperative complications were significantly associated with poorer health-related quality of life. The effect of postoperative complications on quality of life was sustained until at least 12 months after operation. Between admission and 12 months after surgery, 0.012, 0.026, 0.033, and 0.086 QALYs were lost for those experiencing a grade I, II, III, or IV postoperative complication respectively., Conclusion: Postoperative complications have a significant and sustained effect on patients' quality of life after surgery; this effect worsens as the severity of the complications increases., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.) more...

The development and evaluation of an interprofessional education (IPE) pre-professional geriatrics experience involving learners from 10 different health discipline programs is described. The experience provided learners with opportunities to use small-group collaborative approaches in two 3-hour interprofessional sessions. Learners gained exposure to geriatric principles and awareness of the needs of older adults and their families using case studies developed by experienced interprofessional faculty. Learners completed pre- and post-experience surveys and worksheets on their confidence to function in interprofessional teams, knowledge of other disciplines, perceptions of importance of each discipline in providing older adult care, and the qualities considered for a successful team. Data were collected over three offerings of the experience (2016, 2017, 2018) and analyzed using paired sample t-tests and ANOVA. A total of 562 learners participated with outcome measures indicating increased knowledge of older adult services different health professionals provide and increased confidence in knowing when to complete care referrals. Mean increase in learners' confidence to function in interprofessional teams was significant, suggesting the experience was effective in facilitating confidence in functioning and improving views of other disciplines' roles. This experience demonstrated that learners gained exposure to apply geriatric principle skills and critical thinking as interprofessional team members. more...

Background: Medical technologies have the potential to improve quality and efficiency of healthcare. The design of clinical trials should consider participants' perspectives to optimise enrolment, engagement and satisfaction. This study aims to assess patients' perceptions of their involvement in medical device trials, to inform the designs of future medical technology implementation and evaluation., Methods: Four focus groups were undertaken with a total of 16 participants who had participated in a study testing hospital inpatient remote monitoring devices. Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis., Results: Four main themes emerged: patients' motivations for participating in medical device research; patients' perceptions of technology in medicine; patients' understanding of trial methodology; and patients' perceptions of the benefits of involvement in medical device trials. The appeal of new technology is a contributing factor to the decision to consent, although concerns remain regarding risks associated with technology in healthcare settings. Perceived benefits of participating in device trials include extra care, social benefits and comradery with other participants seen using the devices, although there is a perceived lack of confidence in using technology amongst older patients., Conclusion: Future device trials should prioritise information sharing with participants both before and after the trial. Verbal and written information alongside practical demonstrations can help to combat a lack of confidence with technology. Randomised trials and those with placebo- or sham-controlled arms should not be considered as barriers to participation. Study results should be disseminated to participants in lay format as soon as possible, subject to participant permission. more...

Background: Time out of clinical training can impact medical trainees' skills, competence and confidence. Periods of Out of Programme for Research (OOPR) are often much longer than other approved mechanisms for time of out training. The aim of this survey study was to explore the challenges of returning to clinical training following OOPR, and determine potential solutions., Methods: All current integrated academic training (IAT) doctors at the University of Leeds (United Kingdom) and previous IAT trainees undertaking OOPR in the local region (West Yorkshire, United Kingdom)(n = 53) were invited to complete a multidisciplinary survey., Results: The survey was completed by 33 participants (62% response rate). The most relevant challenges identified were completing the thesis whilst transitioning back to clinical work, the rapid transition between full-time research and clinical practice, a diminished confidence in clinical abilities and isolation from colleagues. Potential solutions included dedicated funds allocated for the renewal of lapsed skills, adequate notice of the clinical rotation to which trainees return, informing clinical supervisors about the OOPR trainee returning to practice and a mandatory return to standard clinical days., Conclusions: Addressing these issues has the potential to improve the trainee experience and encourage future trainees to take time out of training for research activities. more...

Background: Despite medical advances, major surgery remains high risk with up to 44% of patients experiencing postoperative complications. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient's mobility. The aim of this study was to evaluate the feasibility, acceptability and clinical outcomes of continuous remote monitoring after major surgery., Methods: The study was a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery were randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring was achieved using the SensiumVitals® wireless patch which is worn on the patient's chest and monitors heart rate, respiratory rate and temperature continuously, and alerts the nurse when there is deviation from pre-set physiological norms. Feasibility was assessed by evaluating recruitment rate, adherence to protocol and randomisation and the amount of missing data. Clinical outcomes included time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of hospital readmission within 30 days of discharge., Results: One hundred and thirty-six patients were randomised between October 2018 and April 2019: 67 to the control group and 69 to the intervention group. Recruitment was completed prior to the 12 month target with a high rate of eligibility and consent. Missing data was limited only to questionnaire responses; no participants were lost to follow-up and only one participant was withdrawn due to loss of capacity. The number of patients classed as 'drop-out' due to design (8.1%) were less than anticipated, and there were no participants who crossed over into the alternative trial allocation group. Seventeen participants in the intervention group (28%) did not adhere to the monitoring protocol. No formal comparisons between arms was undertaken; however, participants had fewer unplanned critical care admissions (1 versus 5) and had a shorter average length of hospital stay (11.6 days (95% confidence interval 9.5-13.7 days) versus 16.2 days (95% confidence interval 11.3-21.2 days)) in the continuous vital signs monitoring group. The time taken to receive antibiotics in cases of sepsis was similar in both arms. A cost-utility analysis indicated that the remote monitoring system was cost-saving when compared to standard NEWS monitoring alone., Conclusions: It is feasible to perform a large-scale randomised controlled trial of continuous remote monitoring after major surgery. Progression to a definitive multicentre randomised controlled trial would be appropriate, taking consideration of factors, such as patient adherence, that might mask the potential benefit of additional monitoring., Trial Registration: ISRCTN registry with study ID ISRCTN16601772 . Registered 30 August 2017. more...

Transitions of care involve multifaceted considerations for patients, which can pose significant challenges if factors like oral health are overlooked when evaluating medication management. This article examines how oral health factors should be considered in medication management of patients who may be at risk for hospital readmission. This article also explores successes and challenges of a pharmacy consult service integrated into a dental clinic practice, and the opportunities within that setting to improve overall patient outcomes including those related to care transitions. more...

The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transmembrane protein transporter is known for conferring resistance to treatment in cancers. Photodynamic therapy (PDT) is a promising anti-cancer method involving the use of light-activated photosensitisers to precisely induce oxidative stress and cell death in cancers. ABCG2 can efflux photosensitisers from out of cells, reducing the capacity of PDT and limiting the efficacy of treatment. Many studies have attempted to elucidate the relationship between the expression of ABCG2 in cancers, its effect on the cellular retention of photosensitisers and its impact on PDT. This review looks at the studies which investigate the effect of ABCG2 on a range of different photosensitisers in different pre-clinical models of cancer. This work also evaluates the approaches that are being investigated to address the role of ABCG2 in PDT with an outlook on potential clinical validation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.) more...

Background: Research waste is a major challenge for evidence-based medicine. It implicates misused resources and increased risks for research participants. The aim of this study was to quantify constituent components of waste in surgical RCTs and explore targets for improvement., Methods: ClinicalTrials.gov was searched for RCTs registered between January 2011 and December 2012 using the keyword 'surgery'. The primary outcome was research waste, defined as non-publication, inadequate reporting or presence of an avoidable design limitation. Serial systematic searches of PubMed and Scopus databases were performed to determine publication status. Adequacy of reporting was assessed using the CONSORT checklist. Avoidable design limitations were evaluated according to the presence of bias and/or the absence of a cited systematic review of the literature., Results: Of 5617 registered RCTs, 304 met all eligibility criteria. Overall, 259 of 304 (85·2 per cent) demonstrated at least one feature of waste. Of these, 221 (72·7 per cent) were published in a peer-reviewed journal and 219 were accessible for full-text review. Only 73 of 131 (55·7 per cent) RCTs with a pharmacological intervention and 24 of 88 (27 per cent) with a non-pharmacological intervention were reported adequately, and 159 of 219 (72·6 per cent) demonstrated an avoidable design limitation. Multicentre (odds ratio 0·31, 95 per cent c.i. 0·11 to 0·88) and externally funded (OR 0·35, 0·15 to 0·82) RCTs were less associated with research waste., Conclusion: This study identified a considerable burden of research waste in surgical RCTs. Future initiatives should target improvements in single-centre, poorly supported RCTs., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.) more...

Background: Continuous vital signs monitoring on general hospital wards may allow earlier detection of patient deterioration and improve patient outcomes. This systematic review will assess if continuous monitoring is practical outside of the critical care setting, and whether it confers any clinical benefit to patients., Methods: MEDLINE ® , MEDLINE ® In-Process, EMBASE, CINAHL and The Cochrane Library were searched for articles that evaluated the clinical or non-clinical outcomes of continuous vital signs monitoring in adults outside of the critical care setting. The protocol was registered with PROSPERO (CRD42017058098)., Findings: Twenty-four studies met the inclusion criteria and reported outcomes on a total of 40,274 patients and 59 ward staff in nine countries. The majority of studies showed benefits in terms of critical care use and length of hospital stay. Larger studies were more likely to demonstrate clinical benefit, particularly critical care use and length of hospital stay. Three studies showed cost-effectiveness. Barriers to implementation included nursing and patient satisfaction and the burden of false alerts., Conclusions: Continuous vital signs monitoring outside the critical care setting is feasible and may provide a benefit in terms of improved patient outcomes and cost efficiency. Large, well-controlled studies in high-risk populations are required to evaluate the clinical benefit of continuous monitoring systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.) more...

Background: Vital signs monitoring is used to identify deteriorating patients in hospital. The most common tool for vital signs monitoring is an early warning score, although emerging technologies allow for remote, continuous patient monitoring. A number of reviews have examined the impact of continuous monitoring on patient outcomes, but little is known about the patient experience. This study aims to discover what patients think of monitoring in hospital, with a particular emphasis on intermittent early warning scores versus remote continuous monitoring, in order to inform future implementations of continuous monitoring technology., Methods: Semi-structured interviews were undertaken with 12 surgical inpatients as part of a study testing a remote continuous monitoring device. All patients were monitored with both an early warning score and the new device. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis., Findings: Patients can see the value in remote, continuous monitoring, particularly overnight. However, patients appreciate the face-to-face aspect of early warning score monitoring as it allows for reassurance, social interaction, and gives them further opportunity to ask questions about their medical care., Conclusion: Early warning score systems are widely used to facilitate detection of the deteriorating patient. Continuous monitoring technologies may provide added reassurance. However, patients value personal contact with their healthcare professionals and remote monitoring should not replace this. We suggest that remote monitoring is best introduced in a phased manner, and initially as an adjunct to usual care, with careful consideration of the patient experience throughout., (Copyright © 2018 Elsevier B.V. All rights reserved.) more...

Background: Early warning scores are widely used to identify deteriorating patients. Whilst their ability to predict clinical outcomes has been extensively reviewed, there has been no attempt to summarise the overall strengths and limitations of these scores for patients, staff and systems. This review aims to address this gap in the literature to guide improvements for the optimization of patient safety., Methods: A systematic review was conducted of MEDLINE ® , PubMed, CINAHL and The Cochrane Library in September 2016. The citations and reference lists of selected studies were reviewed for completeness. Studies were included if they evaluated vital signs monitoring in adult human subjects. Studies regarding the paediatric population were excluded, as were studies describing the development or validation of monitoring models. A narrative synthesis of qualitative, quantitative and mixed- methods studies was undertaken., Findings: 232 studies met the inclusion criteria. Twelve themes were identified from synthesis of the data: Strengths of early warning scores included their prediction value, influence on clinical outcomes, cross-specialty application, international relevance, interaction with other variables, impact on communication and opportunity for automation. Limitations included their sensitivity, the need for practitioner engagement, the need for reaction to escalation and the need for clinical judgment, and the intermittent nature of recording. Early warning scores are known to have good predictive value for patient deterioration and have been shown to improve patient outcomes across a variety of specialties and international settings. This is partly due to their facilitation of communication between healthcare workers. There is evidence that the prediction value of generic early warning scores suffers in comparison to specialty-specific scores, and that their sensitivity can be improved by the addition of other variables. They are also prone to inaccurate recording and user error, which can be partly overcome by automation., Conclusions: Early warning scores provide the right language and environment for the timely escalation of patient care. They are limited by their intermittent and user-dependent nature, which can be partially overcome by automation and new continuous monitoring technologies, although clinical judgment remains paramount., (Copyright © 2017 Elsevier Ltd. All rights reserved.) more...

Aim: To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base., Methods: This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MED-LINE (1950 to June 2016) was conducted. The keywords "osteoporosis", "osteoporotic fracture", "dementia" and "Alzheimer's disease" (AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia (predominantly Alzheimer's type) and osteoporosis., Results: Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies., Conclusion: Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed., Competing Interests: Conflict-of-interest statement: The authors confirm that there are no potential conflicts of interest. There is no financial support to declare. more...

Background: Retraction plays a vital role in optimizing the field of vision in minimal-access surgery. As such, a number of devices have been marketed to aid the surgeon in laparoscopic retraction. This systematic review explores the advantages and disadvantages of the different instruments in order to aid surgeons and their institutions in selecting the appropriate device. Primary outcome measures include operation time, length of stay, use of staff, patient morbidity, ease of use, conversion rates to open surgery, and cost., Methods: Systematic literature searches were performed in MEDLINE, EMBASE, The Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. The search strategy focused on studies testing a retraction device. The selection process was based on a predefined set of inclusion and exclusion criteria. Data were then extracted and analyzed., Results: Out of 1360 papers initially retrieved, 12 articles were selected for data extraction and analysis. A total of 10 instruments or techniques were tested. Devices included the Nathanson's liver retractor, liver suspension tape, the V-List technique, a silicone disk with or without a snake retractor, the Endoloop, the Endograb, a magnetic retractor, the VaroLift, a laparoscope holder, and a retraction sponge. None of the instruments reported were associated with increased morbidity. No studies found increased rates of conversion to open surgery. All articles reported that the tested instruments might spare the use of an assistant during the procedure. It was not possible to determine the impact on length of stay or operation time., Conclusions: Each analyzed device facilitates retraction, providing a good field of view while allowing reduced staff numbers and minimal patient morbidity. Due to economic and environmental advantages, reusable devices may be preferable to disposable instruments, although the choice must be primarily based on clinical judgement., (© The Author(s) 2015.) more...

Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size. more...

Background: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas., Methods: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed., Results: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis., Conclusions: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR. more...

Our previous animal studies showed that maternal Porphyromonas gingivalis infection in a subcutaneous chamber is associated with hepatic and uterine translocation, as well as systemic induction of maternal inflammatory responses, both of which were associated with fetal growth restriction (FGR). However, P. gingivalis-challenged dams had fetuses with either FGR (2 standard deviations below mean weight of nonchallenged dams) or normal weight. Therefore, the objective of this study was to determine whether maternal infection with P. gingivalis compromises normal fetal development via direct placental invasion and induction of fetus-specific placental immune responses characterized by a proinflammatory Th1-type cytokine profile. P. gingivalis-specific DNA was detected in placentas and fetuses of FGR and normal littermates from P. gingivalis-infected dams. Th1- and Th2-type cytokine mRNA as well as tumor necrosis factor alpha and transforming growth factor beta 2 mRNA were examined in placental tissue by using reverse transcription-PCR to determine Th1/Th2 ratios. For eight litters containing both normal-weight and FGR fetuses, P. gingivalis DNA was detected only in the placentas of FGR fetuses. All fetuses and all amniotic fluid samples from infected and control dams were negative for P. gingivalis DNA. mRNA levels of gamma interferon and interleukin-2 (IL-2) were significantly increased in placentas of FGR fetuses, while expression of IL-10 was significantly decreased in the same group. These data indicate that, in P. gingivalis-challenged dams, within each litter there is placenta-specific translocation of P. gingivalis that results in growth restriction of the targeted fetus, which is associated with a shift in the placental Th1/Th2 cytokine balance. more...