Point-of-care lung ultrasound in patients with COVID-19 - a narrative review.

Ultrasound imaging of the lung and associated tissues may play an important role in the management of patients with COVID-19-associated lung injury. Compared with other monitoring modalities, such as auscultation or radiographic imaging, we argue lung ultrasound has high diagnostic accuracy, is ergonomically favourable and has fewer infection control implications. By informing the initiation, escalation, titration and weaning of respiratory support, lung ultrasound can be integrated into COVID-19 care pathways for patients with respiratory failure. Given the unprecedented pressure on healthcare services currently, supporting and educating clinicians is a key enabler of the wider implementation of lung ultrasound. This narrative review provides a summary of evidence and clinical guidance for the use and interpretation of lung ultrasound for patients with moderate, severe and critical COVID-19-associated lung injury. Mechanisms by which the potential lung ultrasound workforce can be deployed are explored, including a pragmatic approach to training, governance, imaging, interpretation of images and implementation of lung ultrasound into routine clinical practice.

A core competency framework for prostate cancer peer navigation.

PURPOSE: Trained peer navigators can offer valuable peer support and mentorship to cancer patients and caregivers due to their highly relevant and unique perspective about the disease experience. In order to define the role of prostate cancer (PC) peer navigators within the cancer care system, it is important to establish the essential competencies of a PC peer navigator. We systematically identified and verified a set of core competencies for PC peer navigators and present a competency framework for PC peer navigators. METHODS: In phase 1, we conducted formative research consisting of a literature review and environmental scan as well as a secondary analysis of qualitative interviews. In phase 2, we drafted and mapped competencies. Finally in phase 3, expert stakeholders completed an anonymous survey to indicate whether they endorsed the competencies and to rank the importance of each competency to the peer navigator role. Open-ended feedback was also provided for each competency. RESULTS: Six core competency domains emerged: (1) self as navigator, (2) communication, (3) knowledge/information, (4) facilitate patient-centred care, (5) eHealth/technology, and (6) caregiver needs. Forty-seven core competency statements were mapped to these domains. Expert stakeholders (n = 27) included cancer survivors, caregivers, and healthcare providers. Most (89%) of core competency statements were endorsed by stakeholders and received high priority ratings, whereas only five of the competencies were less uniformly endorsed. CONCLUSIONS: This is the first attempt to list core competencies for PC peer navigators and may offer guidance for standardizing the PC peer navigator role and training.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015: recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.(AU)

2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Rectal cancer: prognostic indicators of long-term outcome in patients considered for surgery.

PURPOSE: Patients and clinicians seek an accurate prognosis after resectional surgery for rectal cancer. The aim of this study was to determine long-term outcomes after potentially curative surgery for rectal cancer with particular focus on factors associated with longer-term survival that are available to surgeons in the early post-operative setting. METHODS: We conducted a retrospective review of a prospectively gathered database of all primary rectal adenocarcinomas considered for surgery in the University Hospitals of Leicester National Health Service (NHS) Trust between 1998 and 2007. Survival was calculated using a Kaplan-Meier method. Factors thought to be associated with survival were subjected to univariate analysis followed by Cox proportion regression. RESULTS: One thousand and twelve patients with primary rectal adenocarcinoma diagnosed between 1998 and 2007 were identified. Eight hundred and fifty three patients did not have metastases at the time of presentation and 726 patients underwent major resectional surgery. Five-year survival was 66 %. Patients' age, Dukes' stage, UICC stage, nodal involvement and circumferential resection margin status were independently associated with long-term survival on multivariate analysis. CONCLUSION: This is one of the largest series of rectal cancers from a single NHS trust. We have demonstrated that age, Dukes' stage and CRM status are associated with long-term survival. These clinical factors are readily available to the surgeon at the time of first post-operative review and can provide a good clinical guide to prognosis.

A transperineal approach to perineal hernia repair using suture anchors and acellular porcine dermal mesh.

Perineal hernia following major pelvic surgery is a rare but recognised complication. Various surgical approaches to the repair of a symptomatic perineal hernia have been described. We describe the first reported use of the Mitek suture anchors to secure an acellular porcine dermal graft to the ischia during the transperineal repair of a large perineal hernia.

Nonresectional palliative abdominal surgery for patients with advanced colorectal cancer.

OBJECTIVE: Nonresectional palliative abdominal surgery (e.g. defunctioning stoma/bypass) may be appropriate for patients unsuitable for curative resection, to deal with complications of advanced colorectal malignancy such as obstruction. Our aim was to review the outcome of surgery in these patients within our institution. METHOD: All patients undergoing palliative surgery without resection for colorectal carcinoma between July 1998 and January 2007 were identified from our prospectively compiled colorectal cancer database. Data were extracted related to patients' demographics, presentation, tumour site, operative intervention, complications, oncological therapies, length of hospital stay and postoperative survival. RESULTS: One hundred and ninety-three patients were identified with a median age of 79 years (31-94 years). Fifty per cent were operated on an emergent basis for obstruction or perforation, and 50% on an elective basis. One hundred and sixty-nine patients had defunctioning stomas formed of which 156 were loop stomas. Twenty-four patients underwent bypass procedures. Thirty-day mortality rate was 13.5% and postoperative morbidity rate 47%. Median survival was 247 days, with 1-year survival of 38%. Patients undergoing operation on an emergent basis had poorer long-term survival (127 vs 320 days, P = 0.002). CONCLUSION: Nonresectional palliative abdominal surgery is associated with relatively high morbidity and mortality, particularly when performed in the emergency setting. However, in this patient group with a very poor outlook, it may be offered with reasonable survival expectations.

The RAPID protocol enhances patient recovery after both laparoscopic and open colorectal resections.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs can accelerate recovery and shorten the hospital stay after colorectal resections. The RAPID (remove, ambulate, postoperative analgesia, introduce diet) protocol is a simplified ERAS program that consists of a simplified, user-friendly single-page pro forma schedule. This study aimed to evaluate the impact of the RAPID protocol on patients undergoing both laparoscopic and open colorectal resections in two specialized colorectal units. METHODS: A prospective, two-center study assessed 117 age-matched patients undergoing open or laparoscopic colorectal resection to compare the postoperative course for patients using the RAPID protocol with those treated in a traditional manner. RESULTS: Of the 117 patients studied, 70 underwent laparoscopic resection (55 with the RAPID protocol) and 47 underwent open resection (25 with the RAPID protocol). Patients undergoing laparoscopic resections with the RAPID protocol had a significantly shorter hospital stay (p = 0.01) and tolerance of a full diet (p = 0.002). Similarly, patients undergoing open resections with the RAPID protocol also have a significantly shorter hospital stay (p = 0.04). CONCLUSION: The RAPID protocol is a user-friendly, easy, and effective tool that facilitates earlier tolerance of diet and discharge from the hospital for patients undergoing laparoscopic or open colorectal resections.

Colorectal cancer: presentation and outcome in British South Asians.

AIM: Colorectal cancer (CRC) has a lower incidence in patients of South Asian origin compared with British Caucasians. There are however little data available regarding the demographics of these patients, their presentation and outcome. Leicester has a high South Asian immigrant population, and we aim to define any potential differences in presentation, pathogenesis and outcome between our Caucasian and South Asian ethnic groups. METHOD: All patients of South Asian origin were identified from the Leicester CRC database between June 1998 and April 2007. Data were analysed regarding the patients' demographics, the presentation and treatment details, tumour characteristics and clinical outcome. Data were compared with Caucasian patients from the same database. Patients from an ethnic background other than South Asia or Caucasians were excluded from analysis. RESULTS: 3435 patients were included in the analysis, of which 134 (3.9%) were of South Asian ethnicity. 61.9% of South Asian patients were male compared with 56% of Caucasians. South Asians were significantly younger at presentation (61.4 vs 70.6 years, P < 0.001). South Asian patients had significantly more rectal tumours than their Caucasian counterparts (P = 0.002). South Asian patients were more likely to require initial oncological therapy, and were less likely to have resectional surgery than Caucasians (P = 0.006). Of the patients undergoing resectional surgery, the ASA grade, mode of surgery, tumour characteristics and Dukes' stage were similar. There was no difference in 5-year survival between the South Asian and Caucasian patients. CONCLUSION: Patients of South Asian ethnicity are younger at their age of presentation and have a higher proportion of rectal tumours compared with British Caucasian patients. They are more likely to require initial oncological treatment and are less likely to undergo resectional surgery, therefore suggesting more advanced disease at presentation. Overall 5-year survival is the similar.

A case of toxic megacolon in a patient with collagenous colitis.

Collagenous colitis is an uncommon inflammatory bowel disease, the aetiology of which is unknown. We report a case of toxic megacolon in a patient with collagenous colitis, a previously unreported complication.

Enteral Clostridium difficile, an emerging cause for high-output ileostomy.

The loss of fluid and electrolytes from a high-output ileostomy (>1200 ml/day) can quickly result in dehydration and if not properly managed may cause acute renal failure. The management of a high-output ileostomy is based upon three principles: correction of electrolyte disturbance and fluid balance, pharmacological reduction of ileostomy output, and treatment of any underlying identifiable cause. There is an increasing body of evidence to suggest that Clostridium difficile may behave pathologically in the small intestine producing a spectrum of enteritis that mirrors the well-recognised colonic disease manifestation. Clinically this can range from high-output ileostomy to fulminant enteritis. This report describes two cases of high-output ileostomy associated with enteric C difficile infection and proposes that the management algorithm of a high-output ileostomy should include exclusion of small bowel C difficile.

Restorative proctocolectomy. Does ethnicity affect outcome?

OBJECTIVE: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is well-established in the management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). We review outcome of pouch surgery from a single centre, comparing non-South Asian and South Asian Caucasian populations. METHOD: Patients undergoing RPC for UC and FAP during a 10-year period between January 1997 and January 2007 were identified from hospital records. Data were collected retrospectively from case notes on early and long-term results. RESULTS: A total of 107 patients underwent pouch formation for UC (94%) or FAP (6%) and 22 (21%) were from the Asian subcontinent. Eighty-seven (81%) underwent a three-stage procedure and 20 (19%) a two-stage procedure. Postoperative complications occurred in 40 (37%) patients, being major in 11 (10%) patients with relaparotomy required in 9 (8%) with no difference between South Asian and non-South Asian Caucasian patients. Long-term pouch function, with a median of five times over 24 h (range 2-15), was similar between the two groups. The incidence of pouchitis was 57 (53%) and this was significantly greater in the South Asian population [17/21 (77%); 39/86 (46%); P = 0.006]. CONCLUSION: Surgical results were similar in South Asian and non-South Asian Caucasian patients, but the incidence of pouchitis was greater in the former group.

Terminal Ileum Perforation as a Consequence of a Migrated and Fractured Oesophageal Stent.

Covered self-expanding metallic stents are commonly employed to relieve malignant oesophageal obstruction. We report a case of a patient with oesophageal cancer treated by stent insertion and curative chemoradiotherapy with subsequent stent migration to the stomach. The stent fractured with the distal fragment migrating as far as the terminal ileum where it caused perforation of the bowel.

Assessment of a patient consultation questionnaire-based scoring system for stratification of outpatient risk of colorectal cancer.

BACKGROUND: The UK government's fast-track 2-week wait (2WW) rule and colorectal cancer guidelines aimed to detect patients at high risk of having colorectal cancer, but the yield has been poor. A patient consultation questionnaire (PCQ)-based scoring system may be an effective tool for prioritizing colorectal referrals. The aim of this study was to validate the system in a large and ethnically diverse population and to compare it with 2WW referrals. METHODS: Over a 1-year period, all colorectal referrals (2WW and traditional letters) at nine hospitals in Leicestershire were sent a PCQ to complete and return. A weighted numerical score (WNS), which reflects the patient's risk of having colorectal cancer, was calculated and compared with the hospital diagnosis. RESULTS: Of a total of 1422 PCQs returned, 83 patients were diagnosed with colorectal cancer. The 2WW referrals constituted 35.7 per cent of all referrals. The mean WNS of patients with colorectal cancer was significantly higher than that of the other patients (mean 76.3 versus 48.9 respectively; P < 0.001). For similar cancer detection rates (or sensitivity), the specificity of a WNS cut-off of 70 was significantly better than that of the 2WW system (82.7 versus 66.1 per cent; P < 0.001). CONCLUSION: The PCQ-based WNS system improves specificity for detecting colorectal cancer, particularly when the WNS exceeds 70.

Factors that influence the adequacy of total mesorectal excision for rectal cancer.

OBJECTIVE: In 1997 with the start of CRO7 trial it was agreed that adequacy of surgical resection of rectal cancer would be determined by a pathologically determined grading of the mesorectum the so called total mesorectal excision score (TME score). Scores ranged from 1-3 with 3 being a perfect specimen. The aim of this study was to investigate factors which may influence TME scores and establish if local recurrence is related to them. METHOD: Data on all patients undergoing resectional surgery for rectal cancer in our unit are entered prospectively onto a database. Pathology reports of those patients who underwent total mesorectal excision were examined and the TME scores added to the database. Categorical variables were analysed using the chi2 test, continuous variables using ANOVA. Statistical significance was taken as P < 0.05. RESULTS: Between January 2000 and June 2005, 518 patients underwent surgery for adenocarcinoma of the rectum, of these, 287 patients had a total mesorectal excision for mid or lower third tumours under the care of seven colorectal surgeons. All resected specimens were scored by a Consultant GI pathologist. Two hundred and fourteen patients underwent anterior resection and 73 underwent abdomino-perineal resection. The median age of the patients was 73 years (range 38-95 years). One hundred and ninety-four patients were male. Seventy-eight patients were treated with preoperative radiotherapy, 59 short course and 19 long course. TME scores were TME1 n = 30, TME2 n = 99, TME3 n = 158. Fifteen patients developed local pelvic recurrence at 2 years. Total mesorectal excision scores were not statistically influenced by Dukes' stage, width of tumour, preoperative radiotherapy or grade of surgeon. Male patients were statistically more likely to have a TME score of 2 or 3 compared with female P = 0.04. Patients undergoing an anterior resection were statistically more likely to have a TME score of 2 or 3 compared with abdomino-perineal resection P = 0.0001. Tumours with a circumferential resection margin (CRM) of more than 1 mm were more likely to have a TME score of 2 or 3 score (P = 0.0001). There was no relationship between TME and local recurrence (P = 0.966). CONCLUSION: There is no relationship between the TME score in patients undergoing resectional surgery for adenocarcinoma of the rectum and the development of local recurrence at 2 years. Other factors such as CRM involvement are more likely to have an impact on local recurrence. The factors that influence the quality of TME are the operative procedure of anterior resection, male gender and CRM positivity. There appear to be no deleterious effects on the TME score by Specialist Registrars performing the operation under Consultant supervision. While TME scores may be an index of a technical performance, they appear to have little role in predicting future outcomes.

Unreasonable expectations in emergency colorectal cancer surgery.

OBJECTIVES: The recently published ACPGBI colorectal cancer (ACPGBI CRC) scoring system for predicting operative mortality has been suggested as an instrument to improve patient consent procedures and to compare results between centres. This study compares the results of a surgical unit against the standards set by the ACPGBI colorectal cancer model and for emergency surgery, against the p-POSSUM instrument. METHODS: Data for the ACPGBI CRC model were collected prospectively through 2003 at the Leicester Royal Infirmary. Additional data needed for the p-POSSUM was retrospectively collected from case records. The actual mortality was compared with that predicted by the models. RESULTS: Seventy-two colorectal cancer operations were performed during the study period. The observed operative mortality in elective cases was lower, and in emergency cases higher, than predicted by the ACPGBI CRC model. With emergency cases the predicted mortality using P-POSSUM was significantly higher than that using the ACPGBI CRC model, particularly in the presence of faecal contamination. CONCLUSION: The ACPGBI CRC model may be accurate for elective cases, but appears to significantly underestimate predicted mortality in the emergency setting, both actual and predicted by p-POSSUM. This may be due to a failure to incorporate adequate weighting for faecal peritonitis and the associated systemic insult into the ACPGBI model.

Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations.

Constitutively active mutant forms of signaling enzymes provide insight into mechanisms of activation as well as useful molecular tools for probing downstream targets. In this study, point mutations in ERK2 at conserved residues L73P and S151D were identified that individually led to 8-12-fold increased specific activity and in combination reached 50-fold, indicating synergistic interactions between these residues. Examination by mass spectrometry, phosphatase sensitivity, and Western blotting revealed that the mutations enhanced ERK2 activity by facilitating intramolecular autophosphorylation predominantly at Tyr-185 and to a lesser extent at Thr-183 and that phosphorylation at both sites is required for activation. A set of short molecular dynamics simulations were carried out using different random seeds to sample locally accessible configurations. Simulations of the active mutant showed potential hydrogen bonding interactions between the phosphoryl acceptor and catalytic nucleophile, which could account for enhanced intramolecular autophosphorylation. In intact cells, the ERK2 mutants were functionally active in phosphorylating Elk-1 and RSK1 and activating the c-fos promoter. This activity was only partially reduced upon treatment of cells with the MKK1/2 inhibitor, U0126, indicating that in vivo the mechanism of ERK2 activation occurs substantially through autophosphorylation and partially through phosphorylation by MKK1/2.

Pemphigus vulgaris: clinicopathologic review of 33 cases in the oral cavity.

A retrospective study was conducted on all cases of pemphigus vulgaris occurring on oral mucosal surfaces in the files of the Oral Pathology Laboratory at Temple University from 1974 to 1996. A total of 35 biopsies from 33 patients were reviewed, 25 female and eight male. Patient ages ranged from 27 to 79 years; the mean age was 56.5. The most common clinical complaint was of painful ulcers that failed to resolve within several weeks. Thirty patients had no known history of pemphigus, while in three patients a history of pemphigus was known. The most common clinical impression was that of mucous membrane pemphigoid, but the differential diagnosis included other vesiculoerosive conditions.

The effect of pelvic ileal reservoir volume and antiperistaltic reflux on emptying efficiency.

PURPOSE: The emptying efficiency of four different designs of pelvic ileal reservoir was compared using two different techniques of measurement. METHOD: Thirty-four patients were studied one year after restorative proctocolectomy. In each the ileal reservoir was filled with methyl cellulose paste labeled with 51chromium-chromate and technetium Tc 99m-diethylenetriamine pentaacetic acid. Percentage evacuation was calculated from 1) the difference in 51chromium activity between the recovered effluent and the total paste administered and 2) gamma camera measurements of technetium Tc 99m-diethylenetriamine pentaacetic acid activity within the ileal reservoir before and after evacuation. RESULTS: Median evacuation using the 51chromium method was 84, 90, 70, and 75 percent for the W40, W30, J40, and J30 reservoirs respectively. The results were not significantly different from those obtained using the gamma camera: 83, 87, 67, and 71 percent (P = not significant). Patients with either type of W reservoir evacuate isotope-labeled paste more efficiently than patients with J40 reservoirs (P < 0.05 and P < 0.001, respectively) but not J30 reservoirs (P = not significant). However, if the actual volume of paste evacuated during a visit to the lavatory is measured, it is greatest for J40 reservoirs (median, 300 ml compared with 258 ml for W40, 289 ml for W30, and 268 ml for J30; P = not significant). CONCLUSIONS: Gamma camera measurement of ileal reservoir emptying is as accurate as our previous standard technique and provides a qualitative record of pouch evacuation, which may reveal reasons for inefficient emptying. The gamma camera images reveal that the difference in emptying percentage between W and J pouches is because of reflux of paste into the afferent ileum occurring more frequently in J pouches than in W pouches. The effect of this phenomenon on emptying is more than compensated for by the increase in reservoir capacity created by the reflux.