Multicenter Collaborative Study Research Articles

C-KIT Expression in Orbital Cavernous Venous Hemangiomas.

Orbital (slow flow) cavernous venous hemangiomas (OCVH) are the most common benign orbital tumors in adults. The c-KIT is a tyrosine kinase receptor, which is expressed on several types of cells, is thought to play a key role in tumor pathogenesis. The purpose of this study was to evaluate the presence of the receptor c-KIT in OCVH. Our retrospective study examined 16 orbital cavernous venous hemangiomas from 16 cases operated on between 2006–2016 at Emek Medical Center. The mean tumor size was 18.4 mm. Symptoms appeared between 6 months and 22 years before operation. All specimens were analyzed for the c-KIT receptor through immunohistochemistry. The c-KIT was expressed by the endothelium in all 16 preparates. Staining was strong in two cases, moderate in six, and weak in eight cases, with no statistically significant correlation between staining and tumor size (p = 0.69) or the symptom duration (p = 0.15). We conclude that c-KIT may play an important role in the pathogenesis of OCVH. This pilot study is significant in that tumor-targeted therapy such as Imatinib Mesylate and Sunitinib may have a role in treating surgically complicated cases located in the orbital apex. A large multicenter collaborative study is necessary to examine the role of c-KIT in OCVH.

RADI-04. Stereotactic radiosurgery in alveolar soft part sarcoma brain metastasis

BackgroundAlveolar soft part sarcoma (ASPS), although rare, has the highest incidence of brain metastasis amongst all sarcomas. Stereotactic radiosurgery (SRS) has been shown to be a well tolerated and effective treatment of intracranial sarcomatous metastasis. However, there is a paucity of published literature that guides radiation therapy in this condition.MethodsThis is a single centre retrospective review of all ASPS patients with intraparenchymal brain metastasis in our centre treated with stereotactic radiosurgery (SRS). SRS dosing is dichotomised into high and low dose (≥25 Gy and <25 Gy respectively) and outcomes such as local recurrence (LR) and radiation effects are noted. Successful treatment was defined as a lesion that regressed, is stable, or has less than 25% increase in tumour volume. Local recurrence (LR) was defined as increase in tumour volume by more than 25% during follow up.ResultsThere were three patients with 11 ASPS metastatic brain lesions, one of which underwent retreatment. Each lesion was followed up for a mean duration of 12 months (range: 5 – 22 months). Five lesions treated with a high dose regime and six lesions were given low dose. Lesions treated with high dose SRS experienced significantly less LR (20% vs 83.3%, OR 20.0 [95%CI 0.93 – 430), p = 0.036) with no increase in undue symptomatic radiation effects. Retreatment of lesions with LR after initial SRS using a low dose regime was successful, albeit only in the single recurrent lesion.ConclusionsWe conclude that SRS can be used as a first line treatment for ASPS brain metastasis that are not surgically accessible and that using a high dose for treatment is effective and safe. Multicentre collaborative studies can be performed to validate this claim.

Effect of Occupational Therapy Program to Promote Well-Being in People with Experiences of Mental Illness- Quasi-Experimental Study

The aim of this study was to test the effectiveness of an occupational therapy program to promote well-being in people with experiences of mental illness. The method was a multicentre collaborative study. The intervention group participated in an occupational therapy program to promote well-being in addition to the standard program of day hospital/psychiatric occupational therapy, while the control group only participated in the standard program only. Results showed that the intervention group had effects on three factors, including “Positive emotions,” “Willingness to ask for help,” and “Achievement.” The effectiveness of this program needs to be further tested in a randomized controlled trial.

Association of Pharyngocutaneous Fistula With Cancer Outcomes in Patients After Laryngectomy

Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain. To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival. A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years). Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years. In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non-PCF (72%) group was 3% (95% CI, -6% to 12%). The difference in overall survival between the group with PCF (44%) and the non-PCF group (52%) was 8% (95% CI, -2% to 20%). The difference in disease-free survival between PCF and non-PCF groups was 6% (95% CI, -4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control. This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.

Comparisons between retinal vessel calibers and various optic disc morphologic parameters with different optic disc appearances: The Glaucoma Stereo Analysis Study.

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. This study evaluated the retinal vessel calibers and correlations using GSAS fundus photographs between retinal vessels and 38 optic nerve head (ONH) morphologic parameters comprehensively. In all 240 eyes, the mean central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were 138.4 and 216.5 μm, respectively; the CRAE correlated with age, visual field scores and 19 ONH parameters and CRVE correlated with age, intraocular pressure, visual field scores and 11 ONH parameters. Among the different optic disc appearances including focal ischemia (FI) (n = 53, 22%), generalized enlargement (GE) (n = 53, 22%), myopic glaucoma (MY) (n = 112, 47%), and senile sclerosis (SS) (n = 22, 9%), the CRAE did not differ significantly; CRVE was significantly narrower in SS than in FI and MY. In FI, GE, MY, and SS disc types, CRAE correlated with 3, 14, 9, and 2 ONH parameters, respectively, and CRVE corelated with 9, 0, 12, and 6 ONH parameters, respectively. We confirmed previous observations on the effect of retinal vessel narrowing on glaucomatous changes in the ONH and visual field. The associations between retinal vessel caliber and ONH morphologic parameters vary among different optic disc appearances, suggesting different effects of vascular changes in each disc type.

Risk Classification for Overall Survival by the Neutrophil-Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab-A Multicenter Collaborative Study in Japan.

Simple SummaryPembrolizumab improves overall survival (OS) in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas objective response was observed in a modest number of patients (<25%) for this treatment, implying the distinct survival outcomes for those patients. Thus, the optimal risk stratification to predict survival outcomes at the initiation of pembrolizumab treatment would be helpful for physicians. In the present study, we examined a risk model developed using two clinical factors, including the number of metastatic sites and neutrophil–lymphocyte ratio (NLR), for predicting OS at the initiation of pembrolizumab treatment. This risk stratification seemed to be well-balanced (26.5%, 44.3%, and 29.2% in the favorable-risk, intermediate-risk, and poor-risk groups, respectively), and Kaplan–Meier curves illustrated clear discrimination of OS among the risk groups. Since the model proposed in the present study can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

An Overview of the Korean Intermittent Exotropia Multicenter Study by the Korean Association for Pediatric Ophthalmology and Strabismus.

The Korean Intermittent Exotropia Multicenter Study (KIEMS), which was initiated by the Korean Association of Pediatric Ophthalmology and Strabismus, is a collaborative multicenter study on intermittent exotropia in Korea. The KIEMS was designed to provide comprehensive information, including subjective and objective findings of intermittent exotropia in a large study population. A total of 65 strabismus specialists in 53 institutions contributed to this study, which, to date, is one of the largest clinical studies on intermittent exotropia. In this article, we provide a detailed methodology of the KIEMS to help future investigations that may use the KIEMS data.

A multi-center collaborative double-blind study on clinical evaluation of AYUSH-SL in patients receiving mass drug administration for management of chronic filarial lymphedema—study protocol

BACKGROUND: Lymphatic filariasis (LF) is caused by Wuchereria bancrofti, Brugia malayi, or B. timori, the parasitic nematodes that are transmitted through mosquitoes. The World Health Organization has recommended mass drug administration (MDA) as preventive chemotherapy strategy. In Ayurveda, LF has been narrated under the heading Shlipada, and the literature also includes detailed therapeutic measures. AYUSH-SL is a formulation prepared based on the classical information of herbs used in treating LF. MATERIALS AND METHODS: This is a multi-center, prospective, parallel-group, placebo-controlled, double blind interventional study. A total of 180 participants are planned to be recruited, and the duration of the study will be 2.5 years. Diagnosed cases of filariasis (as evidenced by a positive immune-chromatographic card test or enzyme-linked immunosorbent assay or microfilariae (MF) test report) of either sex within the age group of 18–65 years present with features of filarial lymphedema of Grade I and Grade II (lower limbs) will be included in the trial. The study group will be treated with MDA and AYUSH-SL tablet. The control group will receive MDA and a matching placebo. The duration of the therapy will be of 12 weeks, and a last follow-up will be done at the 24th week. OUTCOME MEASURES: The primary outcome measure is reduction of edema computed for analysis by percentage reduction from the baseline at 4th, 12th, and 24th week. The secondary outcome measures include improvement in quality of life (QoL), which will be assessed using the Lymphatic Filariasis Specific QoL Questionnaire, and prevention of recurrence of acute episodes, which will be assessed by probing the presence and severity of episodes in the past 4 weeks. DISCUSSION: The deformities and disability due to filarial lymphedema vanquish physically as well as mentally leading to hardships in normal life. Management of filarial lymphedema is required for preventing disease progression and episodes of adenolymphangitis. The study is expected to provide evidence on the coded Ayurveda drug AYUSH-SL in the management of chronic filarial lymphedema.

Extended surgery for middle bile duct cancer: Results from Japan-Korea collaboration study

It was not clear whether pancreaticoduodenectomy (PD) or bile duct segmental resection (BDSR) was superior for localized middle bile duct cancer (mid-BDC). To investigate the short- and long-term outcomes of mid-BDC patients treated with PD compared to those for BDSR. This was a retrospective, Japanese and Korean multi-center collaboration study (UMIN000017914) based on patients' medical records. A total of 663 patients, including 245 BDSR and 418 PD cases, were enrolled. Postoperative pancreatic fistula incidence, surgical site infection in the organ space, and clinically problematic morbidities were significantly higher in the PD group. However, there was no difference in the mortality rate. Local and lymph node recurrence rates were significantly higher in the BDSR group. Overall survival was significantly longer in the PD group. Subgroup analysis revealed that the PD group had significantly better prognosis in early stage (stage IA/IB) cases which were the best indicators for BDSR, even when R0 resection was achieved. In multivariate analysis, BDSR was an independent poor prognostic factor. Although the inferior short-term outcomes, our data advocate that PD should be the standard procedure for mid-BDCs and that BDSR should be avoided (Hayashi H, et al. J Hepatobiliary Pancreat Sci 2020; 27: 289-298).

Cycling injuries requiring orthopaedic intervention during the first COVID-19 lockdown period: A multi-centre SCottish Orthopaedic Research collaborativE (SCORE) study

IntroductionThe COVID-19 lockdown resulted in decreased vehicle use and an increased uptake in cycling. This study investigated the trends in cycling-related injuries requiring orthopaedic intervention during the COVID-19 lockdown period compared with similar time periods in 2018 and 2019. MethodsData were collected prospectively for patients in 2020 and collected retrospectively for 2019 and 2018, from hospitals within four NHS Scotland Health Boards encompassing three major trauma centres. All patients who sustained an injury as a result of cycling requiring orthopaedic intervention were included. Patient age, sex, mechanism of injury, diagnosis and treatment outcome from electronic patient records. ResultsNumber of injuries requiring surgery 2020: 77 (mean age/years – 42.7); 2019: 47 (mean age/years - 42.7); 2018: 32 (mean age/years – 31.3). Overall incidence of cycling injuries 2020: 6.7%; 2019: 3.0%; 2018: 2.1%. Commonest mechanism of injury: fall from bike 2020 n = 54 (70.1%); 2019 n = 41 (65.1%); 2018 n = 25 (67.6%). Commonest injury type: fracture 2020 n = 68 (79.1%); 2019 n = 33 (70.2%); 2018 n = 20 (62.5%). Commonest areas affected: Upper extremity: 2020 n = 45 (58.5%); 2019 n = 25 (53.2%); 2018 n = 25 (78.1%). Lower extremity: 2020 n = 23 (29.9%); 2019 n = 14 (29.7%); 2018 n = 7 (21.8%). ConclusionA significant increase in the number of cycling related injuries requiring orthopaedic intervention, a greater proportion of female cyclists and an older mean age of patients affected was observed during the COVID-19 lockdown period compared with previous years. The most common types of injury were fractures followed by lacerations and fracture-dislocations. The upper extremity was the commonest area affected.

Erythropoiesis changes with increasing age in the elderly Chinese

Erythropoiesis slowly decreases with increasing age, which may be reflected in red blood cell (RBC) parameters. This multicentre collaborative study aimed to investigate the changes in erythropoiesis with increasing age in a healthy Chinese population. A total of 14,591 healthy individuals (6,713 aged at least 60y and 7,878 aged below 60y) from seven cities across China were enrolled. K2-EDTA anticoagulant blood samples were analysed. The results are presented as median and 2.5-97.5th percentile. RBC parameters showed some differences between the two groups divided by the age of 60 in the Chinese population. The median, 2.5th and 97.5th percentile values of RBC, haemoglobin (HGB) and haematocrit (HCT) in patients aged ≥60y were significantly lower than in those ˂60y. The values of mean cell volume (MCV), mean cell haemoglobin (MCH) and red cell distribution width (RDW) were higher in the group aged ≥60y. Men had significantly higher RBC, HGB, HCT, MCV, MCH and RDW indices than women. The prevalence of anaemia gradually increased with age in men and was higher than that in women after 50. The median haemoglobin and MCV in Nanning and Guangzhou were lower than those in other regions. RBC parameters varied with increasing age and differed between males and females, indicating that erythropoiesis decreases in the elderly Chinese population. Subsequent studies should be conducted for age- and sex-specific reference intervals in healthy elderly Chinese populations.

Propensity-score matched analysis of the efficacy of maintenance/continuous therapy in newly diagnosed patients with multiple myeloma: a multicenter retrospective collaborative study of the Japanese Society of Myeloma.

Maintenance ± consolidation or continuous therapy is considered a standard of care for both transplant-eligible and -ineligible patients with multiple myeloma (MM). However, long-term benefits of such therapy have not yet been clarified in the context of clinical practice. To clarify the efficacy of maintenance/continuous approach, we retrospectively analyzed the cohort data of newly diagnosed MM patients by propensity-score matching based on age, gender, revised International Staging System (R-ISS) stage, and implementation of transplantation to reduce the bias due to confounding variables. Among 720 patients, 161 were identified for each of the maintenance and no maintenance groups. Maintenance/continuous therapy employed immunomodulatory drugs (n = 83), proteasome inhibitors (n = 48), combination of both (n = 29), or dexamethasone alone (n = 1). Progression-free survival (PFS) was significantly prolonged in the maintenance group compared with the no maintenance group (median 37.7 and 21.9months, p = 0.0002, respectively). Prolongation of PFS was observed in both transplanted and non-transplanted patients (p = 0.017 and p = 0.0008, respectively), with standard risk (p < 0.00001), R-ISS stage I (p = 0.037) and stage II (p = 0.00094), and those without obtaining complete response (p = 0.0018). There was no significant benefit in overall survival (OS), but it tended to be better in the maintenance group in non-transplanted patients. Regarding the treatment pattern, the substitution or addition of drugs different from the induction therapy and the combination with immunomodulatory drugs and proteasome inhibitors appeared to be more beneficial for PFS but not OS. These results support the benefit of current maintenance/continuous approach in routine clinical practice in the management of MM.

Residential proximity to pesticide applications in Argentine Patagonia: impact on pregnancy and newborn parameters.

Among residents living close to agricultural fields who are potentially exposed to pesticides, pregnant women and their fetuses are of particular concern for their vulnerability to environmental chemicals. In this collaborative multicenter study, we covered a wide distribution of participants in the most important fruit production zone of north Patagonia (Argentina) to investigate whether maternal residential proximity to fruit croplands with intense pesticide applications (rural group -RG-) is associated with pregnancy complications and alterations in their newborn parameters compared to the urban population (urban group -UG-). A total of 776 pregnant women met the inclusion criteria. The percentage of threatened miscarriage was significantly higher in the RG than in the UG. The percentage of miscarriage, threat of premature labor, intrauterine fetal death, preterm premature rupture of membranes, and intrauterine growth retardation were similar in both groups. Newborn anthropometric parameters were corrected by sex and gestational age prior to statistical analysis. Length at birth and head circumference were lower in the RG than in the UG. Birth weight was similar in both groups. The percentage of head circumference less than the 5th percentile and the ponderal index were greater in the RG than in the UG. Our results suggest that proximity to pesticide applications may increase the risk of pregnancy complications and altered newborn parameters.

MO068RENAL HISTOPATHOLOGY IN CANCER PATIENTS: RESULTS OF A MULTICENTER STUDY

Abstract Background and Aims Some decades ago, patients with cancer were not submitted to invasive procedures because of their short life expectancy. This is one of the main reasons why data about kidney histology in oncological patients with kidney impairment is very scarce: kidney biopsies were not performed in this population. However, renal biopsy is an especially useful diagnostic and prognostic tool in these patients when they develop kidney injury. The aim of our study is to study clinical and histological characteristics of patients with active solid organ malignancy that underwent kidney biopsy in a multicenter cohort. Method We performed a multicenter collaborative retrospective study. Clinical, demographical, and histological data from patients with an active neoplasia or in active cancer treatment who underwent kidney biopsy were collected. Statistics: Quantitative variables are expressed as mean+/-SD (normal distribution) or median (IQ 25-75) (non-normal distribution).Qualitative variables are expressed as percentage. Actuarial survival curves were performed using Kaplan-Meier. Results 94 patients with cancer who underwent a kidney biopsy during the study period, from 9 hospitals were included.63.8% men, 36.2% woman and mean age 66 (SD +/- 10,95) years old. The indications for biopsy were acute renal failure (63.8%), proteinuria (17%), and exacerbation of chronic kidney disease (11.7%). At the time of the renal biopsy, 27.7% patients presented diabetes, 60.6% high blood pressure, 10.6% were on non-steroidal anti-inflammatory drugs treatment, and 74.5% were receiving renin angiotensin system blockers. Malignances were lung (31.9%), intestinal (13.8%) and prostate (8.5%), with 43.6% metastatic cancer. As oncospecific treatment, 33% received chemotherapy, 30.8% immunotherapy (of which 37.93% received more than 1 checkpoint inhibitor (CPI) and 24.13% had immune-related adverse events), 22.4 % specific therapies, 17 % surgery, and 3.2% conservative treatment. Previously to kidney injury, 51.06% presented Cr&amp;gt; 1 mg / dL. At the time of kidney biopsy, median creatinine was 2,63mg/dL [1,75-3,9 (IQ 25-75)], median urine protein/creatinine ratio 795 mg/g [221-3182(IQ 25-75)]; 51.1% presented haematuria and 22.3% nephrotic range proteinuria; 8.5% eosinophiluria and 7.44% hemolytic anemia and /or low platelet. At the time of renal biopsy, 8.5% presented ANCA and 5.31% decrease in C3 / C4 serum levels. The renal biopsy diagnosis was: 40.4% acute interstitial nephritis, followed by acute tubular necrosis (9.6%), thrombotic microangiopathy (6.4%), membranous nephropathy (5.3%) and IgA nephropathy (6.4%). 62.8% received corticosteroids (28.81% pulses) for an average of 5.8 months [3.7-9.1(IQ 25-75)]. 12.8% required kidney replacement therapy. 43.6% showed complete recovery of kidney function at the end of follow-up. Average follow-up 22.59 months. 40.2% of patients died at the end of follow-up and 72.34 % presented chronic kidney disease. As expected, and maybe related to the heterogeneous cancer disease studied, the only factor associated with mortality was the presence of the metastasis at the moment of kidney biopsy (p=0.028). Conclusion Histological kidney diagnosis in patients with active cancer involves various renal disorders, such as acute interstitial nephritis, thrombotic microangiopathy, membranous nephropathy and IgA nephropathy. Renal biopsy in this group of patients provides valuable diagnostic and prognostic information. More studies are needed to expand the consensus in the diagnosis and treatment of oncological patients with renal injury.

Variation in Human Research Ethics Committee and governance processes throughout Australia: a need for a uniform approach.

In Australia, ethics committees across different states vary in application, requirement and process for the ethical review and approval for clinical research. This may lead to confusion and delays in the enablement of multicentre research projects. This study explores the effect of differing processes for Ethics and Governance in the establishment of the CovidSurg-Cancer study during the global COVID-19 pandemic. An anonymous, structured web-based questionnaire was designed using the Research Electronic Data Capture application (REDCap) platform to capture consultant surgeons, fellows, and trainees experience in the ethics application process. 'CovidSurg-Cancer' was an international multicentre collaborative study to assess the impact of COVID-19 on the outcomes of patients undergoing cancer surgery. The ethics process to set up this observational study was used as to explore the differing processes applied across Australia. The CovidSurg-Cancer study was successfully set up in 14 hospitals. Four hospitals approved the study directly as an audit. Of the remaining sites, 10 ethics applications underwent Human Research Ethics Committee review following which two (14%) were subsequently approved as an audit activity and eight hospitals (57%) were given formal ethical approval with waiver of consent. Ethics application acceptance from another Australian Human Research Ethics Committee was provided with six applications; however, only three were reciprocated without the requirement for further agreements. A third of (30%) respondents suggested that the details of the application pathway, process and documentation were unclear. Ethics processes are varied across Australia with considerable repetition. A centralized, harmonized application process would enhance collaborative research.

P100 Recruitment barriers in multicentre collaborative studies as demonstrated by a single unit experience of the Management of Acutely Symptomatic Hernias (MASH) study

IntroductionMASH is a multi-centre prospective cohort study assessing the management of patients presenting with symptomatic abdominal wall hernia. Consenting patients are recruited during acute admission, with telephone follow up at day 30 and 90. We performed a retrospective review of all patients referred to a single general surgical unit with a symptomatic hernia to quantify recruitment rate and identify barriers to recruitment.MethodsPatients meeting the inclusion criteria 1st August to 18th September were identified from prospective handover lists and electronic records and compared to the prospectively compiled screening log. Reason for not enrolment was coded according to protocol with an additional code added for patients not identified at time of admission.Results8/23 (35%) eligible patients were enrolled. 15/23 (65%) were not enrolled due to; Patient not identified at time of admission n = 9 (60%), declined n = 2 (13.3%), too unwell to consent n = 2 (13.3%), translational barrier n = 1 (6.6%) and lacking capacity n = 1 (6.6%). Patients not identified at time of admission included those seen by clinicians not involved in study (new starters and locums) and those discharged directly from A&E with insufficient time and resources to gain consent.ConclusionIn our unit 65% of eligible patients were not recruited, the majority of whom were missed at time of presentation. This study will generate important information on management and outcomes of acute hernias however strategies are required to recognise and mitigate recruitment bias. Staff turnover may be a significant factor in prospective studies, particularly those prolonged during the COVID-19 pandemic.

Dental caries vaccine: An overview

Dental caries is an irreversible microbial disease of the tooth which fulfills the idea of an infectious disease and hence the possibilities of vaccination have been considered. Many pertinent components of vaccine development, such as protein, recombinant or synthetic peptide, or DNA-based active vaccines, as well as mucosal adjuvants, such as heat-labile enterotoxins from Vibrio cholera or Escherichia coli, and chitosan, have proven effective through numerous in vitro and in vivo researches, as well as some human clinical trials. The use of adjuvants and the routes of antigen administration have both been studied to improve the host response. Vaccines such as pGJA-P/VAX, LT derivative/Pi39-512, KFD2-rPAc and SBR/GBR-CMV-nirB are few of the potential vaccines that have been produced and tested in animals in recent years. However, there is still a scarcity of information about the role of caries vaccine in human population. Multicentre collaborative studies and clinical trials of immunologically superior dental caries vaccine formulations are the need of the hour for preventing dental caries.

Clinical Study of 668 Indian Subjects with Juvenile, Young, and Early Onset Parkinson's Disease.

To determine the demographic pattern of juvenile-onset parkinsonism (JP, <20 years), young-onset (YOPD, 20-40 years), and early onset (EOPD, 40-50 years) Parkinson's disease (PD) in India. We conducted a 2-year, pan-India, multicenter collaborative study to analyze clinical patterns of JP, YOPD, and EOPD. All patients under follow-up of movement disorders specialists and meeting United Kingdom (UK) Brain Bank criteria for PD were included. A total of 668 subjects (M:F 455:213) were recruited with a mean age at onset of 38.7 ± 8.1 years. The mean duration of symptoms at the time of study was 8 ± 6 years. Fifteen percent had a family history of PD and 13% had consanguinity. JP had the highest consanguinity rate (53%). YOPD and JP cases had a higher prevalence of consanguinity, dystonia, and gait and balance issues compared to those with EOPD. In relation to nonmotor symptoms, panic attacks and depression were more common in YOPD and sleep-related issues more common in EOPD subjects. Overall, dyskinesias were documented in 32.8%. YOPD subjects had a higher frequency of dyskinesia than EOPD subjects (39.9% vs. 25.5%), but they were first noted later in the disease course (5.7 vs. 4.4 years). This large cohort shows differing clinical patterns in JP, YOPD, and EOPD cases. We propose that cutoffs of <20, <40, and <50 years should preferably be used to define JP, YOPD, and EOPD.

Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95%CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95%CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Study of the pathophysiological mechanisms associated with the onset and course of neurodevelopmental disorders in preterm infants (the PeriSTRESS-PremTEA study): Rationale, objectives, design and sample description

BackgroundThere are few studies exploring the pathophysiological pathways that may condition differentially the emergence/course of neurodevelopmental disorders (ND) in very preterm and extremely preterm newborns (VPTN/EPTN). Furthermore, there are no established biological markers predictive of ND in this population. The aim of this study is four-fold: in two cohorts of VPTN/EPTN (i) to characterize the emergence/course of ND up to corrected-age 6 years, (ii) to identify those factors (from prenatal stages up to age 6 years) that explain the interindividual differences related to emergence/course of ND, (iii) to identify in the first hours/days of life a urinary metabolomic biomarker profile predictive of ND, and (iv) to determine longitudinally variations in DNA methylation patterns predictive of ND. MethodsObservational, longitudinal, prospective, six-year follow-up, multicentre collaborative study. Two cohorts are being recruited: the PeriSTRESS-Valencia-cohort (n=26 VPTN, 18 EPTN, and 122 born-at-term controls), and the PremTEA-Madrid-cohort (n=49 EPTN and n=29 controls). ResultsWe describe the rationale, objectives and design of the PeriSTRESS-PremTEA project and show a description at birth of the recruited samples. ConclusionsThe PeriSTRESS-PremTEA project could help improve early identification of clinical, environmental and biological variables involved in the physiopathology of ND in VPTN/EPTN. It could also help to improve the early identification of non-invasive ND biomarkers in this population. This may allow early ND detection as well as early and personalised intervention for these children.