Sociodemographic variables as predictors of adverse outcome in SARS-CoV-2 infection: an Irish hospital experience.

INTRODUCTION: Our hospital found itself at the epicentre of the Irish COVID-19 pandemic. We describe the organisational challenges faced in managing the surge and identified risk factors for mortality and ICU admission among hospitalised SARS-CoV-2-infected patients. METHODS: All hospitalised SARS-CoV-2 patients diagnosed between March 13 and May 1, 2020, were included. Demographic, referral, deprivation, ethnicity and clinical data were recorded. Multivariable regression, including age-adjusted hazard ratios (HR (95% CI), was used to explore risk factors associated with adverse outcomes. RESULTS: Of 257 inpatients, 174 were discharged (68%) and 39 died (15%) in hospital. Two hundred three (79%) patients presented from the community, 34 (13%) from care homes and 20 (8%) were existing inpatients. Forty-five percent of community patients were of a non-Irish White or Black, Asian or minority ethnic (BAME) population, including 34 Roma (13%) compared to 3% of care home and 5% of existing inpatients, (p < 0.001). Twenty-two patients were healthcare workers (9%). Of 31 patients (12%) requiring ICU admission, 18 were discharged (58%) and 7 died (23%). Being overweight/obese HR (95% CI) 3.09 (1.32, 7.23), p = 0.009; a care home resident 2.68 (1.24, 5.6), p = 0.012; socioeconomically deprived 1.05 (1.01, 1.09), p = 0.012; and older 1.04 (1.01, 1.06), p = 0.002 were significantly associated with death. Non-Irish White or BAME were not significantly associated with death 1.31 (0.28, 6.22), p = 0.63 but were significantly associated with ICU admission 4.38 (1.38, 14.2), p = 0.014 as was being overweight/obese 2.37 (1.37, 6.83), p = 0.01. CONCLUSION: The COVID-19 pandemic posed unprecedented organisational issues for our hospital resulting in the greatest surge in ICU capacity above baseline of any Irish hospital. Being overweight/obese, a care home resident, socioeconomically deprived and older were significantly associated with death, while ethnicity and being overweight/obese were significantly associated with ICU admission.

Recent advances in the understanding of celiac disease: therapeutic implications for the management of pediatric patients.

Celiac disease (CD) is an autoimmune condition occurring in genetically susceptible individuals characterized by inflammatory injury to the mucosa of the small intestine after the ingestion of wheat glutens or related barley and rye products. Originally thought to be highly prevalent only in Northern European populations, growing evidence indicates a much higher prevalence in many other regions, including the US as well as South America, North Africa, and Asia. The growing awareness that pediatric patients may present with quite diverse and protean manifestations and the significant impact of CD on childhood development has prompted efforts to increase CD awareness for the early diagnosis and treatment of this disease. The current diagnostic criteria for CD requires characteristic histologic findings in small bowel biopsies and clinical remission when placed on a gluten-free diet. Serologic testing for CD can provide additional support for the diagnosis of CD or a means to assess efficacy and adherence to a gluten-free diet. The mainstay of treatment remains the institution of a gluten-free diet. However, patients with refractory CD may require treatment with immunosuppressant medications. With the increased identification of specific gluten epitopes and understanding of the pathogenesis of CD, future therapies may rely on genetically altering gluten proteins, immunization techniques, or therapies focused on either the development of specific immune tolerance or regulation of mucosal inflammation.

The risk of lymphoma in the treatment of inflammatory bowel disease with immunosuppressive agents.

Immunosuppressive agents have become an established part of the therapeutic armamentarium for inflammatory bowel disease (IBD). However, when used in transplant recipients or for other indications, agents that suppress or modulate the immune system (immunomodulators) have been associated with an increased risk of lymphoma. Fortunately, in part because of the lower doses used in IBD patients, the risk of lymphoma in IBD patients appears to be significantly less than that associated with renal and hepatic transplant-related immunosuppression. Whether the risk of azathioprine or 6-mercaptopurine associated lymphoma in IBD is real or relates to the underlying disease remains unclear. The results of several recent large well designed population-based studies suggest that the lymphoma risk associated with azathioprine and 6-mercaptopurine therapy is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is far outweighed by the clinical benefit of immunomodulator therapy in IBD. While the issue of lymphoma risk is likely to become more relevant with the growing number of biologic and immunomodulators being tested in clinical trials for IBD, early post-marketing surveillance data on infliximab suggests that the lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine.

Smoking and immunomodulators do not influence the response or duration of response to infliximab in Crohn's disease.

OBJECTIVE: Clinical predictors for infliximab response are still unknown. Identifying predictors of response to infliximab in Crohn's disease may improve our selection of patients. METHODS: Two hundred patients with luminal (61%) or fistulous (39%) Crohn's disease and at least 6 months of follow-up following a total of 416 infliximab infusions were evaluated. Clinical response and duration of response were the primary endpoints. RESULTS: Patients with fistulous disease had a higher response rate (83% versus 70%, P = 0.044) and a significantly longer duration of response compared with patients with luminal disease (17.4 versus 10.1 wks, P = 0.017). For luminal disease, nonsmokers and smokers had similar response rates (74% versus 64%, P = 0.5) and similar durations of response (9.4 wks versus 8.4 wks P = 0.6) while patients taking concurrent immunomodulators had similar response rates compared with those not taking immunomodulators (74% versus 71%, P = 0.9) and similar durations of response (10.4 wks versus 10.6 wks, P = 0.9). For fistulous disease, response rates (89% versus 83% P = 0.9) and duration of response (16.9 wks versus 10.1 wks, P = 0.10) were similar between nonsmokers and smokers and concurrent immunomodulators had no effect on response (89% versus 86%, P = 0.9) or duration of response (19.8 wks versus 15.4 wks, P = 0.46). Multivariable analysis confirmed that neither smoking, corticosteroids, immunomodulator therapy, gender, age, age of disease onset, disease duration, nor luminal disease location significantly influenced response or duration of response. CONCLUSIONS: Patients with fistulous disease had a higher response rate and a significantly longer duration of response compared with patients with luminal disease. However, among patients with luminal or fistulous disease, neither smoking nor immunomodulators had any effect on response or duration of response.

New technology for endoscopic retrograde cholangiopancreatography: improving safety, success, and efficiency.

Known and documented factors attributable to ERCP-related complications include the experience and technique of the endoscopist as well as anatomic and pathologic factors pertaining to the papilla. In an effort to minimize trauma, facilitate deep entry to the biliary system, and improve the efficiency of therapeutic ERCP, new cannulation, sphincterotomy, and guide wire devices have been developed, based on principles of safe and successful therapeutic ERCP learned over the years. By totally re-engineering familiar accessories into smaller, more flexible, and more versatile devices, the 0.025-inch guide wire-based DASH system attempts to minimize the trauma at deep CBD cannulation and thereby increase the safety and success of achieving deep cannulation and sphincterotomy. Limited clinical experience to date suggests that the DASH system can provide full-function ERCP while reducing risks and costs. Attention to cannulation has led to the development of the RX Biliary System which provides the endoscopist and the assistant with increased control of the guide wire and exchange compared with traditional devices, resulting in less stress, less hand and wrist force used for contrast injection, and easier guide wire management, all of which have been shown in clinical trials to improve the speed and efficiency of ERCP while reducing complications.

Celiac disease.

Timely diagnosis and treatment of celiac disease is important not only to improve the immediate quality of life of the patient but also to decrease the long-term risks of untreated celiac disease. A large Finnish study showed that the 5-year survival among patients who strictly adhered to a gluten-free diet was similar to that of the general population. Growth and development in infants and children proceed normally with continued gluten avoidance, and in adults many of the disease complications including osteopenia are avoided. However, peripheral neuropathy, ataxia, and severe osteopenia, particularly in the setting of secondary hyperparathyroidism, usually persist. Enteropathyassociated T-cell lymphoma is widely recognized as a complication of celiac disease, and gluten restriction has been shown to significantly decrease the risk of this malignancy to the level of the general population. Whether gluten restriction is beneficial or should be recommended for patients with asymptomatic disease remains controversial. However, the available evidence suggests that this treatment is always indicated in patients showing celiac enteropathy, at least to prevent the possible long-term complications of this condition. Despite a dearth of evidence presently to support population-wide screening for celiac disease, patients at high-risk for celiac disease should be screened based on symptoms, family history, and associated conditions, as morbidity from subclinical disease in young patients has been demonstrated.

Endoscopic assessment of inflammatory bowel disease: colonoscopy/esophagogastroduodenoscopy.

Endoscopy plays an important role in the initial diagnosis of IBD, including the evaluation of disease severity, activity, and extent. The implications of complete mucosal healing further confirm the function of endoscopy in the follow-up of IBD patients. The use of therapeutic endoscopy, for example stricture dilatation, can avoid the need for bowel resection. Modalities such as capsule endoscopy, EUS, NBI, CE, and other emerging techniques are likely to have an increasing role in the management of IBD, particularly in the area of dysplasia surveillance and treatment.

Intravenous, contrast-enhanced MR colonography using air as endoluminal contrast agent: impact on colorectal polyp detection.

PURPOSE: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). MATERIALS AND METHODS: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. RESULTS: Twenty-four polyps were detected in eighteen patients with CC (5 polyps ≥ 10 mm, 4 polyps 6-9 mm, 15 polyps ≤ 5 mm). MRC was 66.7% (12/18) sensitive and 96.4% (27/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5/5) and 100% (19/19), respectively, for lesions greater than 10mm, 100% (4/4) and 100% (20/20) for lesions 6-9 mm, and sensitivity of 20% (3/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9/9) and 100% (15/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n=16) of patients preferred MRC as a future screening test compared to 33% (n=15) for CC. CONCLUSION: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps ≥ 6 mm in size. Further studies are warranted.

Parallel imaging enhanced MR colonography using a phantom model.

PURPOSE: To compare various Array Spatial and Sensitivity Encoding Technique (ASSET)-enhanced T2W SSFSE (single shot fast spin echo) and T1-weighted (T1W) 3D SPGR (spoiled gradient recalled echo) sequences for polyp detection and image quality at MR colonography (MRC) in a phantom model. Limitations of MRC using standard 3D SPGR T1W imaging include the long breath-hold required to cover the entire colon within one acquisition and the relatively low spatial resolution due to the long acquisition time. Parallel imaging using ASSET-enhanced T2W SSFSE and 3D T1W SPGR imaging results in much shorter imaging times, which allows for increased spatial resolution. MATERIALS AND METHODS: Using two porcine colon phantoms each with eight simulated 3-10-mm "polyps," baseline reference sequences acquired without ASSET (6-mm slices and readout bandwidth [BW] 62 kHz) were compared with 11 SSFSE and 8 SPGR sequences acquired with 2-fold ASSET acceleration. ASSET-enhanced SSFSE and SPGR sequences comprised BW/matrix combinations ranging from 20-62 kHz/256-352x256, respectively, with slice thicknesses adjusted from 3.0 to 4.5 mm to maintain a 23-26-second acquisition time and 30 cm slab thickness. Two experienced radiologists viewed the datasets in a randomized, blinded fashion. RESULTS: Compared to reference sequences, ASSET-enhanced SSFSE and SPGR sequences facilitated better polyp detection and had similar overall image quality and per-phantom specificity. The two best ASSET-enhanced SSFSE (3 and 4.5 mm slices, each with BW of 62.5 kHz and 352x256 matrices) and three best ASSET-enhanced SPGR BW/slice thickness/matrix combinations of 31 kHz/4.4 msec/192x256; 62/3.4/192x256; and 62/4.0/192x256, respectively, permitted detection of all polyps>or=5 mm. CONCLUSION: Parallel imaging using ASSET-enhanced T2W SSFSE and T1W 3D SPGR improves the ability to detect significant colon polyps in an MRC phantom model.

Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

BACKGROUND: Recent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults. METHODS: Five cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis. RESULTS: Thirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers. CONCLUSION: Administration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.

CT colonography in 546 patients with incomplete colonoscopy.

PURPOSE: To retrospectively evaluate the positive predictive value (PPV) of computed tomographic (CT) colonography performed in patients who were referred for further examination after incomplete colonoscopy. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board; informed consent was waived. We identified 546 consecutive patients (mean age, 64.1 years; 401 [73.4%] women) who underwent CT colonography after incomplete colonoscopy between November 1999 and December 2002. A retrospective chart review was performed if CT colonography depicted endoscopically nonvisualized lesions 6 mm or greater in diameter. Repeat colonoscopy rate, endoluminal findings, and PPV of CT colonography were determined. Subsequent colonoscopic findings were used as the reference standard. RESULTS: In 72 (13.2%) patients, CT colonography depicted 88 endoscopically nonvisualized lesions 6 mm or greater. Of 11 patients reported to have 12 masses (> or =20 mm), at subsequent colonoscopy, one patient had no mass. Eighteen patients had 23 large (10-19-mm) polyps that they were suspected of having, and 47 patients had 53 medium (6-9-mm) polyps that they were suspected of having. At a median follow-up of 31 months (range, 6-42 months), 45 (63%) of 72 patients underwent follow-up colonoscopy because of their CT colonographic findings. Rates of repeat colonoscopy for masses, large polyps, and medium polyps were 100%, 94%, and 45%, respectively. Per-patient and per-lesion PPVs of CT colonography for masses, large polyps, and medium polyps were 90.9% and 91.7%, 64.7% and 70%, and 33.3% and 30.4%, respectively. CONCLUSION: CT colonography has the potential to become an accepted technique for evaluation of the nonvisualized part of the colon after incomplete colonoscopy, and it can increase the diagnostic yield of masses and clinically important polyps in this part of the colon.

Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice.

Endoscopy plays an integral role in the diagnosis, management, and surveillance of inflammatory bowel disease (IBD). Because there is no single pathognomonic test that establishes the diagnosis of IBD, endoscopy is useful in establishing the diagnosis, excluding other etiologies, distinguishing Crohn's disease from ulcerative colitis, defining the patterns, extent, and activity of mucosal inflammation, and obtaining mucosal tissue for histologic evaluation. In established IBD, endoscopy helps define the extent and severity of involvement, which in turn influences medical and surgical decisions, aids in targeting medical therapies, and allows for the management of IBD-related complications. Furthermore, endoscopy plays a key role in the surveillance of patients with long-standing colitis who are at increased risk for dysplasia and the development of colorectal cancer.