Adapting the investigation of patients on urgent suspected cancer pathway with lower gastrointestinal symptoms across Wales during COVID-19.

INTRODUCTION: The COVID-19 pandemic necessitated the introduction of revised diagnostic pathways for assessing urgent suspected cancer (USC) referrals. Combinations of faecal immunochemical testing (FIT) and minimal preparation computed tomography (CT) scans (MPCT) were used to manage referrals and prioritise access to clinical services or invasive tests. The effectiveness of these pathways across Wales is evaluated in this study. METHODS: All consecutive patients referred from primary care on the USC pathway between 15 March and 15 June 2020 were included to reflect the effect of full lockdown measures. Data collected included demographics, presenting symptom(s), investigations and timelines and patient outcomes up to 90 days following initial referral. RESULTS: A total of 1,050 patients across eight sites in Wales were included. Of these 1,050 patients, 52.6% were female with median age 68 (21-97) years; 50.5% had first-line clinical review, of which 61.1% were virtual consultations; 49.5% had primary investigations; 26.7% of patients had FIT and 13.1% had MPCT. COVID-response pathways achieved a 29.9% reduction in use of colonoscopy as first-line investigation and 79% of patients avoided face-to-face consultations altogether during this first wave of the pandemic. Overall, 6.8% of USC referrals were diagnosed with colorectal cancer (CRC). Median timescale from diagnosis to treatment for CRC was 65 (4-175) days. The negative predictive value (NPV) for FIT in this cohort was 99.6%. MPCT as the first modality had a NPV of 99.2%. CONCLUSION: A modified investigation pathway helped maintain cancer diagnosis rates during the pandemic with improved resource utilisation to that used prepandemic.

Cocaine Abuse: An Unusual Association.

Cocaine addiction is a common problem in the adolescent and the young adults, pharmacologic interventions to reverse the effects of which do not exist. Neurological complications of cocaine abuse, such as seizures, headache, ischemic or hemorrhagic stroke, or subarachnoid hemorrhage, can be disastrous as a result of uncontrolled vasoconstriction and vasculitic damage. The lone occurrence of subdural hematoma in the absence of any other intracranial hemorrhagic complication is rarely seen in patients of cocaine abuse. We wish to share our experience of one such patient who presented to us with an unusual combination of the widespread cerebral infarction and subdural hematoma.

Hughes Abdominal Repair Trial (HART) - Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial.

BACKGROUND: Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. METHODS/DESIGN: This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. DISCUSSION: A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions. TRIAL REGISTRATION NUMBER: ISRCTN 25616490 . Registered on 1 January 2012.

Does an enhanced recovery programme add value to laparoscopic colorectal resections?

PURPOSE: Enhanced recovery programmes (ERP) are now becoming integral to the management of patients undergoing colorectal resection. The benefits of ERP in patients undergoing open colorectal resections have been well recognized; however, the value of ERP in patients undergoing laparoscopic resections is still uncertain. This study was undertaken to assess the impact of ERP in our unit where nearly 90 % of elective colorectal resections are performed laparoscopically. METHODS: A prospectively maintained database of all patients undergoing colorectal resections between Jan 2008 to December 2012 was analysed. The ERP programme was introduced in Aug 2010. The primary outcome measure was post-operative length of stay. Secondary outcome measures were post-operative morbidity and mortality. RESULTS: A total of 506 patients underwent major colorectal resections in the study period (282 patients since introduction of ERP). There were no demographic differences between the pre-ERP and post-ERP groups of patients. The median length of stay prior to the introduction of ERP was 6 days (right-sided resections = 6, left-sided resections = 7.5 and rectal resections = 5.5). For post-ERP, the median length of stay was 5 days (right = 5.5, left = 5 and rectal = 4). Patients who had their laparoscopic procedure converted to open had a course similar to open resections. The morbidity and mortality was lesser in the ERP group but did not reach statistical significance. CONCLUSION: The introduction of an ERP adds additional value in laparoscopic colorectal resections, with further reductions in morbidity and length of stay.

Long-term outcome of prucalopride for chronic constipation: a single-centre study.

AIM: Newer 5-hydroxytryptamine agonists, such as prucalopride, have been demonstrated to be effective in the short term for treatment of chronic constipation. To date, few studies have investigated their medium- and long-term effectiveness. METHOD: An analysis was carried out of a prospectively maintained database of all patients started on prucalopride for chronic constipation between April 2011 and April 2014. Cleveland Clinic Constipation Score (CCCS) questionnaires were administered before starting treatment with prucalopride and at the first follow-up visit to assess change in CCCS scores in 50 randomly selected patients. RESULTS: A total of 155 patients (median age: 47 years; seven men) were started on prucalopride in this period. Of these, 16 (10%) had slow-transit constipation, 31 (20%) had obstructive defaecation syndrome and 30 (19%) had a combination of both. Of these 155 patients, 78% patients were on three or more laxatives at the time of starting prucalopride. Patients were started on 1 mg or 2 mg according to their age. The median follow-up period was 24 (range: 4-40) months. At the first follow-up visit, 106 (68%) patients reported good symptomatic improvement, whereas the remainder had no response. Third of initial responders showed decreased efficacy after a median duration of 6 months and needed regular laxatives/irrigation. Of the 50 patients who filled in the CCCS questionnaires (15 patients were nonresponders), 32 (64%) reported improved scores with a median improvement of two points per criterion. CONCLUSION: This study provides evidence that prolonged use of prucalopride is effective in achieving a sustained benefit in the majority of patients.

Ethnomedicinal plants of Kathua district, J&K, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural products, especially those derived from plants, continue to provide new and important leads in the drug discovery process. The first step in drug discovery is to document material traditionally used to treat an ailment. Documentation of such knowledge will lead to its conservation and facilitate future research on medicinal plant safety and efficacy to validate traditional use. The present study was undertaken with an aim to document the ethnomedicinal plants of Kathua district. MATERIAL AND METHODS: The data were quantitatively analysed using indices like use-value (UV), informant consensus factor (ICF) and fidelity level (Fl). RESULTS: A total of 112 informants (78 males and 34 females) were interviewed. They were using a total of 197 plants from 87 families and 174 genera for the ethnomedicinal purposes. The most dominant families were Fabaceae, Asteraceae and Lamiaceae. The most important plants of the study site on the basis of use-value were Mentha longifolia, Curcuma domestica, Zingiber officinale, Ocimum tenuiflorum, Adiantum capillus-veneris, Viola odorata, Mentha arvensis and Acorus calamus. The diabetes treatment had the maximum consensus (0.96 ICF) among the informants. Other important categories with high ICF values were gastrointestinal disorders and respiratory disorders. Total 23 species recorded 100% Fl. Medicinal plants with high Fl were Brassica rapa, Plumbago zeylanica, Punica granatum, Catharanthus rosea, Tinospora cordifolia, Acacia catechu, Aegle marmelos, Abrus precatorius, Oxalis corniculata, Nicotiana plumbaginifolia, Achillea millefolium, Tamarindus indica, Taxus baccata and Butea monosperma. CONCLUSION: The plants with high UV and Fl like M. longifolia, C. domestica, Z. officinale, O. tenuiflorum, A. capillus-veneris, A. calamus, B. rapa, P. zeylanica, C. rosea, T. cordifolia, A. catechu, O. corniculata, N. plumbaginifolia, A. millefolium, T. indica, T. baccata and B. monosperma should be analysed for pharmacological components and discovery of new drugs.

Sciatic nerve division: a cadaver study in the Indian population and review of the literature.

INTRODUCTION: The sciatic nerve is the largest nerve, with a long course in the inferior extremity. Its division into the tibial and common peroneal nerves can occur at any level from the sacral plexus to the inferior part of the popliteal space. These anatomical variations may contribute to clinical conditions such as piriformis syndrome, sciatica and coccygodynia. METHODS: This study was performed on cadavers in order to study the level of sciatic nerve division. The inferior extremities of 43 cadavers were classified into six groups depending on the level of sciatic nerve division in the gluteal region, the upper, middle and lower parts of the back of the thigh, and the popliteal fossa. RESULTS: The highest incidence of sciatic nerve division (40.7 percent) was observed in the lower part of the posterior compartment of the thigh. In 34.9 percent of the specimens, the sciatic nerve was divided into tibial and common peroneal nerves in the popliteal fossa. 16.3 percent of extremities showed sciatic nerve division proximal to its entrance in the gluteal region. CONCLUSION: In sciatic nerve neuropathies, the extent of neurological deficits depends on the level of sciatic nerve division. Sciatic nerve division into tibial and common peroneal components at a higher level can result in the involvement of only one out of the two divisions from sciatic neuropathy. It can also result in a failure of the sciatic nerve block while performing popliteal block anaesthesia.

Crohn's disease: systematic review of assessment of disease severity and its relevance to surgery.

BACKGROUND: The aims of treatments for Crohn's disease are symptom control by medical or surgical means and improvement in health-related quality of life (HRQOL). A wide number of classification systems, instruments of disease activity measurement (DAM) and HRQOL are available, but few are used in routine surgical practice. OBJECTIVE: To review the validity of DAM and HRQOL instruments and their applicability to surgically treated patients. METHOD: A systematic literature search was undertaken to identify these instruments. Qualifying articles were used to determine the construct, content and criterion validity of the instruments identified with respect to surgically treated patients. RESULTS: Thirteen disease activity indices and 11 HRQOL assessment tools were identified. Construct validity was demonstrated throughout but concerns of content and criterion validity were noted. CONCLUSION: None of the current disease activity or HRQOL tools can be used without potential bias in a trial of surgical vs medical therapy as the items included favour the outcomes experienced following medical therapy. A more balanced assessment tool in the setting of a multidisciplinary trial is needed.

Isolation and characterization of the notch ligand delta4.

Notch signaling plays a critical role in a variety of developmental programs. In vertebrates, the complexity of the process is underscored by the existence of multiple Notch receptors and multiple ligands, each of which displays a distinct expression profile. Furthermore, the ligands can be subdivided into two families, the Serrate/Jagged family and the Delta family. Here we present the isolation of a novel Notch ligand, Delta4. Expression analyses indicate that mouse Delta4 is highly expressed in the eye and lung during embryogenesis and in the heart, lung, liver, and kidney of the adult. Functionally, Delta4 is indistinguishable from Jagged1 in its abilities to inhibit myogenesis and to stimulate transcription through Notch1 and the DNA binding protein CSL.

Update on surgical removal of choroidal neovascularization.

Surgical management of choroidal neovascularization may offer patients with subretinal membranes another therapeutic option. Current techniques allow extraction of subretinal membranes, but not all patients have favorable clinical outcomes with such an approach. This article reviews the current state of subretinal surgery and attempts to summarize those characteristics that may predict good surgical results. Vitreoretinal surgical techniques for the management of subretinal membranes are reasonably well established. Certain characteristics of choroidal neovascularization have been identified that may suggest favorable surgical outcomes; however, no randomized prospective data are yet available to show the role of these procedures. The National Institutes of Health-sponsored Submacular Surgery Trials are designed to determine whether surgery or observation is better for eyes with subfoveal choroidal neovascularization in presumed ocular histoplasmosis syndrome or age-related macular degeneration and in eyes with age-related macular degeneration-associated hematomas.

A combination light-pipe, soft-tipped suction, and infusion cannula instrument for macular translocation.

PURPOSE: To describe a combination light-pipe, soft-tipped suction needle, and infusion cannula instrument for use in macular translocation surgery. METHODS: Macular translocation surgery was performed in human cadaver and live rabbit eyes with a combination light-pipe, soft-tipped suction needle, and infusion cannula instrument. RESULTS: A combination light-pipe, soft-tipped suction needle, and infusion cannula can be used for macular translocation. This instrument is useful for relocating the retina after a 360 peripheral retinotomy is created. It can also be used for macular translocation with the scleral imbrication technique when superior movement of the fovea is required. When used in combination with another soft-tipped suction needle instrument, this surgical instrument allows precise bimanual placement of the retina with simultaneous infusion of liquid perfluorocarbon for fixating the macula to its new location. CONCLUSION: A combination light-pipe, soft-tipped suction needle, and infusion cannula instrument may be a useful tool for macular translocation surgery.

Retinopathy progression and visual outcomes after phacoemulsification in patients with diabetes mellitus.

PURPOSE: To determine the rate of progression of diabetic retinopathy following phacoemulsification surgery and to determine if surgeon experience and/or surgical duration adversely affect visual outcome. METHODS: A retrospective review of 150 eyes of 119 diabetic patients who underwent phacoemulsification surgery over a 5-year period was performed. Data collected included patient age, sex, type and duration of diabetes, diabetic control, associated systemic health factors, preoperative visual acuity and retinopathy grade, duration of surgery, intraoperative complications, and postoperative course. The effect of these factors on visual outcome and rate of retinopathy progression was studied. Resident and private cases were compared. RESULTS: The visual acuity improved by two or more lines in 117 eyes (78%). Ninety-three eyes (62%) had a final visual acuity greater than or equal to 20/40. Retinopathy progression was seen in 37 eyes (25%) followed up for 6 to 10 months. Preoperative nonproliferative diabetic retinopathy, prolonged surgical duration, and limited surgical experience were statistically associated with retinopathy progression. CONCLUSIONS: The visual results and rate of retinopathy progression after phacoemulsification surgery in our series do not appear to differ significantly from those reported using other techniques. Nonproliferative diabetic retinopathy, longer surgical duration, and surgical inexperience resulted in an increased rate of retinopathy progression.

Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogen-activated protein kinase.

p38 is a member of the mitogen-activated protein (MAP) kinase superfamily activated by stress signals and implicated in cellular processes involving inflammation and apoptosis. Unlike the extracellular signal-regulated kinases (p42 and p44 MAP kinases), which are stimulated by insulin in many cell types, p38 activity is inhibited by insulin in postmitotic fetal neurons for which insulin is a potent survival factor (Heidenreich, K. A., and Kummer, J. L. (1996) J. Biol. Chem. 271, 9891-9894). These data suggested that insulin's effects on neuronal survival are mediated by inhibition of a p38-mediated apoptotic pathway. To better understand the relationship between p38 activity and cell survival, we induced apoptosis in two cell lines and examined the ability of insulin or a specific p38 inhibitor (a pyridinyl imidazole compound PD169316) to block p38 activity and cell death. In Rat-1 fibroblasts grown in the presence of serum, p38 activity was undetectable by immune complex assays, and the number of apoptotic cells was very low (<0.5%). After the removal of serum for 16 h, p38 activity was markedly elevated, and apoptosis increased by 14-15-fold. Insulin (50 ng/ml) inhibited p38 activity by approximately 70% and blocked apoptosis by at least 80%. PD169316 also blocked p38 enzyme activity and apoptosis by approximately 80%. Similar results were obtained in differentiated PC12 cells that were deprived of nerve growth factor (NGF) for 16 h. In the presence of NGF, p38 activity and the number of apoptotic cells was very low (approximately 1.0%). After NGF withdrawal, p38 activity was selectively elevated and apoptosis increased to 15%. Both insulin and PD169316 markedly blocked the increase in p38 activity and apoptosis. The MAP kinase kinase inhibitor, PD98059, had no effect on apoptosis in Rat-1 fibroblasts and only partially blocked apoptosis in PC12 cells. PD98059 did not influence insulin's ability to block apoptosis, indicating that the extracellular signal-regulated kinase pathway does not mediate insulin's survival effects. These data further support the role of p38 in cellular apoptosis and support the hypothesis that insulin promotes cell survival, at least in part, by inhibiting the p38 pathway.

Bioactive murine and human interleukin-12 fusion proteins which retain antitumor activity in vivo.

Interleukin-12 (IL-12) is unique amongst cytokines in being a disulfide-linked heterodimer of two separately encoded subunits (p35 and p40). We expressed single chain IL-12 proteins from retroviral constructs in which the two IL-12 subunits were linked by a 6-15 amino acid polypeptide linker, with deletion of the 22 amino acid leader sequence of the trailing subunit. The murine fusion protein IL-12.p40.L.delta p35 containing a (Gly4Ser)3 linker was stably expressed, bioactive in vitro, and had an apparent specific activity comparable to that of native and recombinant IL-12. Western blotting confirmed that murine IL-12.p40.L.delta p35 retained the linking polypeptide sequences. The analogous human IL-12.p40.L.delta p35 fusion protein containing a Gly6Ser linker was bioactive with an apparent specific activity comparable to recombinant human IL-12. In a preexisting CMS-5 tumor model, CMS-5 cells secreting either native or fusion protein forms of IL-12 prolonged survival and led to complete tumor regression.

Characterization of V2O5-AlPO4 catalysts by 51V and 1H magic-angle spinning solid-state nuclear magnetic resonance spectroscopy.

Amorphous aluminum orthophosphate is used as a carrier for preparing a series of V2O5-AlPO4 catalysts with varying vanadia content. The catalysts were characterized by solid-state 51V and 1H magic-angle spinning nuclear magnetic resonance (MAS NMR), electron spin resonance (ESR) and X-ray diffraction (XRD). The XRD patterns of the catalysts remained amorphous at all loadings studied. 51V Solid-state NMR spectra revealed the presence of V2O5 microcrystallites at higher vanadia loadings. The 1H MAS NMR spectra of the catalysts showed a maximum consumption of support hydroxyl groups at 6 wt.-% V2O5 indicating the completion of a monolayer at this composition.

Some aspects of the bionomics of Culex quinquefasciatus (Diptera: Culicidae) in Rajahmundry town, Andhra Pradesh.

From January 1991 to December 1992 the adult and immature populations of Culex quinquefasciatus were monitored in selected localities of Rajahmundry town. The larval density per dip ranged from 1.1 in September to 25.3 in October and the pupal density from 1.2 to 8.4 in October. Two high peaks of adult density in a year were observed during the study. Infective mosquitoes were recorded only in November 1991 and August 1992. Cx. quinquefasciatus landing on human bait was maximum between 2200 to 2400 hours and they preferred to land on body site followed by legs, hands and face in that order. The anthropophilic index was 79.5 per cent. Ratio of Female: Male mosquitoes was 5:1.

Solid-state 27Al and cross-polarization 13C magic-angle spinning nuclear magnetic resonance characterisation of aluminas derived from basic aluminum succinate.

Solid-state 27Al and cross-polarization (CP) 13C magic-angle spinning nuclear magnetic resonance (MAS NMR) was used to characterise aluminas obtained by calcining basic aluminium succinate at different temperatures. In basic aluminium succinate, aluminium is in the tetrahedral coordination only. However, in both X-ray amorphous and gamma-aluminas aluminium is in the tetrahedral and octahedral coordination. The intensity of the aluminium peaks is at a maximum for samples calcined at 700 degrees C. 13C CP MAS NMR indicates the bonding of Al with carbon of the carboxylate group in basic aluminium succinate. Samples calcined at 400-870 degrees C do not give 13C spectra.