Acute Medicine: How will we grow? - An analysis of organisational capabilities for quality improvement, research & education from SAMBA 2021.

BACKGROUND: Education, research, and Quality Improvement (QI) are key enablers for high quality care. We aimed to map the capability of Acute Medical Units (AMUs) to facilitate excellence in these areas. METHODS: AMUs were surveyed in an organisational questionnaire within the Society for Acute Medicine Benchmarking Audit 2021. RESULTS: 143 units participated. 80 units had a QI lead, 24 had a research lead and 99 had a medical education lead. 15 units had all three leadership roles. Most QI work considered service structure rather than changes in processes or care outcomes. CONCLUSION: The organisational capability of AMUs in the strategic areas considered is variable. Improving leadership and disseminating learning could help build a strategic foundation for acute medicine to grow.

Society for Acute Medicine's Patients: Learning from Experience Report (SAM-PLER) A service evaluation of patient reported experience in Acute Medicine - establishing the feasibility of a quality improvement collaborative.

Patient reported experience measures (PREMS) are a key part of measured quality. There is no tool currently used in the UK in Acute Medicine. On the 8th of September 2022 10 units based in England, Scotland and Wales collected data for the validated PREM, alongside the EQ-5D and variables from the Society for Acute Medicine's Benchmarking Audit (SAMBA) dataset. 365 patients were screened, 200 were included (55%): 159 patients from AMUs and 41 from SDEC units. Overall experience of patients was rated 8.5/10, patients rated their experience of safety, trust and listening highly. Collection of PREMS was feasible. Further research is required to link experience to clinical outcome and explore tools that capture experience of patients with altered mental status.

Society for Acute Medicine Benchmarking Audit 2021 (SAMBA21): assessing national performance of acute medicine services.

INTRODUCTION: The Society for Acute Medicine Benchmarking Audit 2021 (SAMBA21) took place on 17th June 2021, providing the first assessment of performance against the Society for Acute Medicine's Clinical Quality Indicators (CQIs) within acute medical units since the start of the COVID-19 pandemic. METHODS: All acute hospitals in the UK were invited to participate. Data were collected on unit structure, and for patients admitted to acute medicine services over a 24-hour period, with follow-up at 7 days. RESULTS: 158 units participated in SAMBA21, from 156 hospitals. 8973 patients were included. The number of admissions per unit had increased compared to SAMBA19 (Sign test p<0.005). An early warning score was recorded within 30 minutes of hospital arrival in 77.4% of patients. 87.4% of unplanned admissions were seen by a tier 1 clinician within 4 hours of arrival. Overall, the medical team performed the initial clinician assessment for 36.4% of unplanned medical admissions. More than a third of medical admissions had their initial assessment in Same Day Emergency Care (SDEC) in 25.4% of hospitals. 62.1% of unplanned admissions were seen by two other clinical decision makers prior to consultant review. Of those unplanned admissions requiring consultant review, 67.8% were seen within the target time. More than a third of unplanned admissions were discharged the same day in 41.8% of units. CONCLUSION: Performance against the CQIs for acute medicine was maintained in comparison to previous rounds of SAMBA, despite increased admissions. There remains considerable variation in unit structure and performance within acute medical services.

Length of stay in Acute Medical Admissions: Analysis from the Society for Acute Medicine Benchmarking Audit.

INTRODUCTION: Medical admissions to hospital represent a diverse range of patients, from those managed on ambulatory pathways through Same Day Emergency Care (SDEC) services, to those requiring prolonged inpatient admission. An understanding of current patterns of admission through acute medicine services and patient factors associated with longer hospital admission is needed to guide service planning and improvement. METHODS: Data from the Society for Acute Medicine Benchmarking Audit (SAMBA) 2021 were analysed. Patients admitted to acute medicine services during a 24-hour period on 17th June 2021 were included, with data recording patient demographics, frailty score, acuity and follow-up of outcomes after seven days. RESULTS: 8101 unplanned medical admissions were included, from 156 hospitals. 31.6% were discharged without overnight admission; the median hospital performance was 30.1% (IQR 19.3-39.3%). 22.1% of patients remained in hospital for more than 7 days. Those remaining in hospital for more than 48 hours and for more than seven days were more likely to be aged over 70, to be frail, or to have a NEWS2 of 3 or more on arrival to hospital. CONCLUSION: The proportion of acute medical attendances receiving overnight admission varies between hospitals. Length of stay is impacted by patient factors and illness acuity. Strategies to reduce inpatient service pressures must ensure effective care for older patients and those with frailty.

Perceptions of anonymised data use and awareness of the NHS data opt-out amongst patients, carers and healthcare staff.

BACKGROUND: England operates a National Data Opt-Out (NDOO) for the secondary use of confidential health data for research and planning. We hypothesised that public awareness and support for the secondary use of health data and the NDOO would vary by participant demography and healthcare experience. We explored patient/public awareness and perceptions of secondary data use, grouping potential researchers into National Health Service (NHS), academia or commercial. We assessed awareness of the NDOO system amongst patients, carers, healthcare staff and the public. We co-developed recommendations to consider when sharing unconsented health data for research. METHODS: A patient and public engagement program, co-created and including patient and public workshops, questionnaires and discussion groups regarding anonymised health data use. RESULTS: There were 350 participants in total. Central concerns for health data use included unauthorised data re-use, the potential for discrimination and data sharing without patient benefit. 94% of respondents were happy for their data to be used for NHS research, 85% for academic research and 68% by health companies, but less than 50% for non-healthcare companies and opinions varied with demography and participant group. Questionnaires showed that knowledge of the NDOO was low, with 32% of all respondents, 53% of all NHS staff and 29% of all patients aware of the NDOO. Recommendations to guide unconsented secondary health data use included that health data use should benefit patients; data sharing decisions should involve patients/public. That data should remain in close proximity to health services with the principles of data minimisation applied. Further, that there should be transparency in secondary health data use, including publicly available lists of projects, summaries and benefits. Finally, organisations involved in data access decisions should participate in programmes to increase knowledge of the NDOO, to ensure public members were making informed choices about their own data. CONCLUSION: The majority of participants in this study reported that the use of healthcare data for secondary purposes was acceptable when accessed by NHS. Academic and health-focused companies. However, awareness was limited, including of the NDOO. Further development of publicly-agreed recommendations for secondary health data use may improve both awareness and confidence in secondary health data use.

Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed "secondary use". The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing.Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about 'Opt-out' schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.

BACKGROUND: This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus. METHODS: All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days. RESULTS: Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions. CONCLUSION: Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.

Applying a COVID Virtual Ward model, assessing patient outcomes and staff workload.

A COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW.

Acute, non-COVID related medical admissions during the first wave of COVID-19: A retrospective comparison of changing patterns of disease.

COVID-19 may have altered the case-mix of non-COVID acute medical admissions. Retrospective analysis of acute medical admissions to University Hospitals Birmingham NHS Foundation Trust, showed that medical admissions decreased in April 2020 compared to April 2019. The proportion of young adults, non-cardiac chest pain, musculoskeletal conditions and self-discharges decreased. The proportion of admissions due to alcohol misuse, psychiatric conditions, overdoses and falls increased. There were a higher number of patients admitted to ICU and greater inpatient mortality but not once COVID diagnoses were excluded. There was a significant change in hospitalised case-mix with conditions potentially reflecting social isolation increasing and diagnoses which rarely require hospital treatment, reducing. This analysis will help inform service planning.

Society for Acute Medicine Benchmarking Audit 2019 (SAMBA19): Trends in Acute Medical Care.

INTRODUCTION: The eighth Society for Acute Medicine Benchmarking Audit (SAMBA19) took place on Thursday 27th June 2019. SAMBA gives a broad picture of acute medical care in the UK and allows individual units to compare their performance against their peers. METHOD: All UK hospitals were invited to participate. Unit and patient level were collected. Data were analysed against published Clinical Quality indicators (CQI) and standards. This was the biggest SAMBA to date, with data from 7170 patients across 142 units in 140 hospitals. RESULTS: 84.5% of patients had an Early Warning Score measured within 30 minutes of arrival in hospital (SAMBA18 84.1%), 90.4% of patients were seen by a competent clinical decision maker within four hours of arrival in hospital (SAMBA18 91.4 %) and 68.6% of patients were seen by a consultant within the timeframe standard (SAMBA18 62.7%). Ambulatory Emergency Care is provided in 99.3% of hospitals. 61.8% of patients are initially seen in the Emergency Department (ED). Since SAMBA18 death rates and planned discharge rates, while the use of NEWS2 increased from 2.5% to 59.2% of hospitals. CONCLUSION: SAMBA19 highlighted the evolving complexity of acute medical pathways for patients. The challenge now is to increase sample frequency, assess the impact of SAMBA open a broader debate to define optimal CQIs.

Acute care service performance during winter: report from the winter SAMBA 2020 national audit of acute care.

The Winter Society for Acute Medicine Benchmarking Audit (SAMBA) provides the first comparison of performance within acute medicine against clinical quality indicators during winter, a time of increased pressure and demand on acute services. 105 hospitals participated in Winter SAMBA, collecting data over 24-hours on 30th January 2020. 5626 patients were included. Participating units saw a median of 48 patients (range 13-131). Comparison between Winter SAMBA and SAMBA19 found less patients had an early warning score within 30 minutes during winter (74.3% vs 78.9%) and less were seen by a clinical decision maker within four hours (84.9% vs 87.9%). Unplanned admissions represented a higher proportion of workload (92.5% vs 90.1%). Patients were more likely to have a NEWS2 score of 3 or higher (30.1% vs 25.7%). Performance is poorer in winter, and patients are more unwell, needing prompt treatment. Services should ensure high quality care can be maintained through times of increased pressure, including winter.

Serum lipase for assessment of pancreatic trauma.

PURPOSE: Pancreatic enzymes are routinely measured during reception of trauma patients to assess for pancreatic injury despite conflicting evidence on their utility. The aim of this study was to investigate the utility of routine initial serum lipase measurement for the diagnosis of acute pancreatic trauma. MATERIALS AND METHODS: Lipase measurements were introduced as part of the trauma pathology panel and requested on all patients who presented to an adult major trauma service and met trauma call-out criteria. Clinical records of these patients were extracted from the trauma registry and retrospectively reviewed. The performance of an initial serum lipase level measured on presentation to detect pancreatic trauma was determined. RESULTS: There were 2,580 patients included in the study, with 17 patients diagnosed with pancreatic trauma. An elevated lipase was recorded in 390 patients. Statistically significant associations were observed for elevated lipase in patients with pancreatic trauma, head injury, acute alcohol ingestion and massive blood transfusion. As a test for pancreatic trauma, an abnormal serum lipase result had a specificity of 85.3 % (95 % CI 83.8-86.6), sensitivity of 76.5 % (95 % CI 49.8-92.2), positive predictive value of 3.3 % (95 % CI 1.8-5.8) and negative predictive value of 99.8 % (95 % CI 99.4-99.9). Higher cut-offs of serum lipase did not result in better performance. CONCLUSIONS: A normal serum lipase result can be a useful adjunct to exclude pancreatic injury. A positive lipase result, regardless of the cut-off used, was not reliably associated with pancreatic trauma, and should not be used to guide further assessment.

Facilitated early ileostomy closure after rectal cancer surgery: a case-matched study.

BACKGROUND: The aim of this study was to evaluate the outcomes of an early stoma closure protocol facilitated by Seprafilm wrapping of defunctioning ileostomies compared with a similar group of patients with conventional stoma formation and closure. METHODS: Consecutive patients undergoing defunctioning ileostomy following rectal resection with pelvic anastomosis were planned for early closure and had their ileostomy wrapped in Seprafilm at the time of formation. Stoma closure was performed at 4-6 weeks if water-soluble contrast enema showed no evidence of leak, and the patient's physiological parameters had been optimized. Patients were matched for age, gender, American Society of Anaesthesiologists score, neoadjuvant treatment and procedure, with patients undergoing conventional ileostomy formation and closure. Outcomes were compared using the 2-tailed Mann-Whitney U test and Fisher's exact test. RESULTS: Following resection, twenty-two patients (69 %) were suitable for early closure and underwent stoma closure at a median of 37 days (range 25-90 days). Seprafilm-wrapped ileostomies were closed earlier than the conventional ileostomies (median 55 days (range 25-250 days) versus 213 days (range 86-352 days), p < 0.001). There was no difference between the groups as regards length of hospital stay or complications following ileostomy closure. Eighteen Seprafilm stoma patients and 22 conventional stoma patients received adjuvant chemotherapy. Median time to starting chemotherapy from resection was 10 versus 8.5 weeks, respectively (p = 0.36). CONCLUSIONS: An early stoma closure protocol facilitated by Seprafilm wrapping of the ileostomy is practical, does not increase morbidity and significantly reduces the time with a stoma for the patient. An early stoma closure protocol did not significantly delay in the commencement of chemotherapy.

Traumatic adrenal gland injury: epidemiology and outcomes in a major Australian trauma center.

INTRODUCTION: Adrenal gland injury (ADGI) is quite rare and mostly associated with other organ injuries secondary to blunt thoracoabdominal trauma. Bilateral ADGI has severe consequences if not discovered in the treatment course of trauma victims. PURPOSE: To review our experience of management of ADGI, epidemiology, and outcomes in a major Australian trauma institute. METHODS: A retrospective analysis of all patients presenting with thoracoabdominal trauma to the Alfred Hospital who had been diagnosed with adrenal gland injury between July 2001 and July 2007. RESULTS: Of 3,921 patients with blunt thoracoabdominal injuries, 2.4% were identified with blunt ADGI (70 males and 26 women, age range 15-85 years). Right adrenal injuries occurred in 72.9%, left adrenal injuries in 22.9%, and bilateral ADGI in 4.2%. Computed tomography (CT) scan findings revealed 82.2% of acute injuries to be hyperdense hematoma expanding and distorting the adrenal gland. Periadrenal stranding and hemorrhagic changes around the adrenal limbs were seen in 12.5%. Oval or round lesions were seen in 3.1%. Surgery was performed in 25% of the study group for associated thoracoabdominal injuries. Patients with left adrenal gland injury had higher rates of mortality and morbidity, and length of stay. CONCLUSION: ADGI is being increasingly recognized with the widespread use of CT scan in the evaluation of multitrauma patients. ADGI is usually self-limiting and typically managed nonoperatively. Acute adrenal insufficiency should be considered and investigated in case of unexplained hypotension in uni- or bilateral ADGI.

Efficient detection of Alport syndrome COL4A5 mutations with multiplex genomic PCR-SSCP.

We have performed effective mutation screening of COL4A5 with a new method of direct, multiplex genomic amplification that employs a single buffer condition and PCR profile. Application of the method to a consecutive series of 46 United States patients with diverse indications of Alport syndrome resulted in detection of mutations in 31 cases and of five previously unreported polymorphisms. With a correction for the presence of cases that are not likely to be due to changes at the COL4A5 locus, the mutation detection sensitivity is greater than 79%. The test examines 52 segments, including the COL4A6/COL4A5 intergenic promoter region, all 51 of the previously recognized exons and two newly detected exons between exons 41 and 42 that encode an alternatively spliced mRNA segment. New genomic sequence information was generated and used to design primer pairs that span substantial intron sequences on each side of all 53 exons. For SSCP screening, 16 multiplex PCR combinations (15 4-plex and 1 3-plex) were used to provide complete, partially redundant coverage of the gene. The selected combinations allow clear resolution of products from each segment using various SSCP gel formulations. One of the 29 different mutations detected initially seemed to be a missense change in exon 32 but was found to cause exon skipping. Another missense variant may mark a novel functional site located in the collagenous domain.

Oxidative neuropathology and putative chemical entities for Alzheimer's disease: neuroprotective effects of salen-manganese catalytic anti-oxidants.

Considerable evidence exists that the brains of individuals with Alzheimer's disease are subject to elevated levels of oxidative stress, particularly in regions exhibiting pathological damage. A major contributor to this oxidative stress appears to be the inflammatory process. Activation of rodent microglial cells by LPS or beta-amyloid peptide results in a marked up-regulation of inducible nitric oxide synthase (iNOS) and corresponding nitric oxide (NO) production. Elevated levels of iNOS are also observed in the brains of Alzheimer patients. The reaction of NO with superoxide leads to the generation of the highly reactive and damaging peroxynitrite free radical species. Peroxynitrite appears to play a key role in the generation of an oxidative stress in the Alzheimer brain as evidenced by widespread nitrotyrosine immunoreactivity. We have employed SIN-1 as a peroxynitrite generating system in cell cultures in order to characterize the effects of this free radical on neurons. SIN-1 treatment of primary rat hippocampal neurons in culture results in neurotoxicity by a necrosis mechanism according to electron microscopic criteria. One approach to limiting peroxynitrite mediated damage is to limit superoxide production. An approach we have evaluated is treatment with salen manganese compounds, a class of catalytic antioxidant compounds which behave as superoxide dismutase (SOD)/catalase mimetics to detoxify superoxide. A number of such salen manganese compounds, including EUK-8 and EUK-134, can markedly protect primary rat cortical neurons from hydrogen peroxide mediated oxidative stress. Such salen manganese compounds can similarly afford marked neuroprotection to an oxidative stress imposed by SIN-1, potentially attributable at least in part to their inherent SOD activity. The salen manganese SOD/catalase mimetics represent a promising class of catalytic antioxidant for attenuating oxidative stress.

News coverage of alcohol and other drugs in U.S. college newspapers.

This study investigated the substance use-related content of a sample of student-run college newspapers. Two independent coders examined 157 news stories, features, editorials, commentaries, letters, photographs, and cartoons. Items about alcohol appeared in one out of every two issues, while items about other drugs appeared in one out of every five issues. Basic information about alcohol and other drug (AOD) use was reported in about one-fifth of the items, while three-fourths dealt with social, legal, safety, or health problems associated with AOD use, especially alcohol consumption. Just over half referred to some type of control policy, most often an enforcement action. Around one-fourth mentioned educational efforts to promote AOD prevention. Very few dealt with detection, intervention, or treatment. Most college newspapers are missing good opportunities for more extensive coverage of AOD issues that would better inform their readers, especially about factors contributing to campus AOD problems and specific program and policy options.

High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.

Expression of mRNA for type IV collagen alpha1, alpha5 and alpha6 chains by cultured dermal fibroblasts from patients with X-linked Alport syndrome.

COL4A5 mutations causing X-linked Alport syndrome (XLAS) are frequently associated with absence of the alpha3, alpha4,alpha5 and alpha6 chains of type IV collagen from basement membranes and increased amounts of the alpha1(IV) and alpha2(IV) chains in glomerular basement membrane. Although many COL4A5 mutations have been described in XLAS, the mechanisms by which these mutations influence the basement membrane appearance of chains other than alpha5(IV) remain poorly understood. In this study, we used dermal fibroblasts from eight normal individuals and nine males with XLAS to test the hypotheses that COL4A5 mutations increase transcription of COL4A1 and suppress transcription of COL4A6. Ribonuclease protection assays revealed that alpha1(IV), alpha5(IV) and alpha6(IV) transcripts were expressed in cultures of dermal fibroblasts. The mRNA levels for alpha1(IV) in eight of nine patients with XLAS were not increased compared to controls; one patient with a large COL4A5 deletion showed significant elevation of alpha1(IV) mRNA levels. No differences in steady-state mRNA levels for alpha6(IV) were found when XLAS fibroblasts were compared with controls, even though little or no alpha6(IV) protein was detectable at the dermal-epidermal junction by immunofluorescence study. This finding suggests that post-transcriptional events account for the absence of alpha6(IV) in the Alport dermal-epidermal junction.

Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM.

Mycoplasma arthritidis, an agent of rodent arthritis, produces a potent superantigen (SAg), MAM. Previous work established that MAM is presented to T cells by murine H-2E or the homologous human HLA-DR molecules and that lymphocytes lacking a functional H-2E molecule fail to respond to MAM. Recently, more potent and purified preparations of MAM of known protein content have become available. This enabled us to more effectively compare the response of MAM with that of other SAgs by using lymphocytes from mice whose cells express different H-2A and HLA-DQ molecules. Here we demonstrate that cells from some H-2E-negative mouse strains respond to higher concentrations of MAM. By use of inbred, congenic, and recombinant mice, we show that these differences are, in fact, exercised at the level of the major histocompatibility complex (MHC) and that allelic polymorphisms at H-2A influence reactivity to MAM. In addition, polymorphisms at HLA-DQ, the human homolog of H-2A, also influence responsiveness to MAM. Cells expressing DQw6 (HLA-DQA1*0103 and DQBI*0601 chains) gave much higher responses to MAM than did cells expressing DQw8 (DQA1*0301 and DQB1*0302 chains). In fact, responses of lymphocytes expressing DQB1*0601 chains homozygously were as high as those observed for cells expressing a functional H-2E molecule. Murine lymphocytes responded less well to staphylococcal enterotoxin B (SEB) and SEA, but mouse cells expressing human MHC molecules gave much higher responses. The patterns of reactivity observed with cells expressing the various murine and human alleles differed for MAM, SEB, and SEA, suggesting that each of these SAgs interacts with different regions or residues on MHC molecules. It has been hypothesized that SAgs might play a role in susceptibility to autoimmune disease. Allelic polymorphisms at MHC loci might therefore influence susceptibility to autoimmune disease by affecting immunoreactivity to specific superantigens.

Common ancestry of three Ashkenazi-American families with Alport syndrome and COL4A5 R1677Q.

Mutations in the basement membrane collagen gene COL4A5 cause the progressive renal glomerular nephropathy and typical hearing loss that occur in X-linked Alport syndrome. Nearly all cases involve distinct mutations, as expected for an X-linked disease that significantly reduces the fitness of affected males. A few exceptional COL4A5 mutations appear to be associated with a reduced disease severity and may account for a significant proportion of late-onset Alport syndrome in populations where a founder effect has occurred. The novel mutation reported here, COL4A5 arg1677gln, has been detected in three independently ascertained Ashkenazi-American families, causes a relatively mild form of nephritis with typical onset in the fourth or fifth decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.