Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

The impact of timing modified natural cycle frozen embryo transfer based on spontaneous luteinizing hormone surge.

PURPOSE: To evaluate whether adjusting timing of modified natural cycle frozen embryo transfer (mNC-FET) 1 day earlier in the setting of a spontaneous LH surge has an impact on pregnancy outcomes. METHODS: This retrospective cohort study evaluated all mNC-FET with euploid blastocysts from May 1, 2016 to March 30, 2019, at a single academic institution. Standard protocol for mNC-FET included ultrasound monitoring and hCG trigger when the dominant follicle and endometrial lining were appropriately developed. Patients had serum LH, estradiol, and progesterone checked on day of trigger. If LH was ≥ 20 mIU/mL, trigger was given that day and FET was performed 6 days after surge (LH/HCG+6), with the intent of transferring 5 days after ovulation. If LH was < 20 mIU/mL, FET was performed 7 days after trigger (hCG+7). Primary outcomes included clinical pregnancy and live birth rates. To account for correlation between cycles, a generalized estimating equation (GEE) method for multivariable logistic regression was used. RESULTS: Four hundred fifty-three mNC-FET cycles met inclusion criteria, of which 205 were in the LH/HCG+6 group and 248 were in the HCG+7 group. The overall clinical pregnancy rate was 64% and clinical miscarriage rate was 4.8%, with similar rates between the two groups. The overall live birth rate was 60.9% (61.0% in LH/HCG+6 group and 60.9% in HCG+7 group). After implementing GEE, the odds of CP (aOR 0.97, 95% CI [0.65-1.45], p = 0.88) and LB (aOR 0.98, 95% CI [0.67-1.45], p = 0.93) were similar in both groups. CONCLUSIONS: In our study cohort, mNC-FET based on LH/HCG+6 versus HCG+7 had similar pregnancy outcomes.

Quantitative Study of the Beliefs and Attitudes Toward Organ Donation and the Opt-Out System Among the Sikh Community in the United Kingdom.

In the United Kingdom, there is a paucity donors from ethnic minorities; however, the number of recipients from ethnic minorities is increasing annually. Following implementation of the opt-out system (OOS) in Wales, a wider debate has started whether the system should be adopted elsewhere in the United Kingdom. We studied Sikh opinion with regard to organ donation and the OOS. METHODS: An anonymous survey was completed by Sikhs in phase 1 paper-based forms and in phase 2 online questionnaires. Data were analyzed using multinomial regression. RESULTS: A total of 268 responses were analyzed; 82.8% said they would donate an organ to anyone; however, 62.1% were not registered organ donors and of those not registered 57.6% did not have sufficient knowledge about the donation process. On multinomial regression, independent variables associated with acceptability of organ donation were awareness of organ shortage, knowing a donor in the immediate family, higher education level, and knowing a successful transplant recipient (all P < .05). Approximately 1 in 2 Sikhs do not understand presumed consent and a majority of 60.1% disagree with the OOS. CONCLUSIONS: Significant barriers exist to donation; there is lack of awareness of the OOS and donation process. Targeted intervention is required to address these barriers.

Understanding and coping with diversity in healthcare.

In the healthcare sector, race, ethnicity and religion have become an increasingly important factor in terms of patient care due to an increasingly diverse population. Health agencies at a national and local level produce a number of guides to raise awareness of cultural issues among healthcare professionals and hospitals may implement additional non-medical services, such as the provision of specific types of food and dress to patients or the hiring of chaplains, to accommodate the needs of patients with religious requirements. However, in an attempt to address the spiritual, cultural and religious needs of patients healthcare providers often assume that ethnic minority groups are homogenous blocks of people with similar needs and fail to recognize that a diverse range of views and practices exist within specific groups themselves. This paper describes the example of the Sikh community and the provision of palliative care in hospitals and hospices. Although, the majority of patients classifying themselves as Sikhs have a shared language and history, they can also be divided on a number of lines such as caste affiliation, degree of assimilation in the west, educational level and whether baptized or not, all of which influence their beliefs and practices and hence impact on their needs from a health provider. Given that it is unfeasible for health providers to have knowledge of the multitude of views within specific religious and ethnic communities and accounting for the tight fiscal constraints of healthcare budgets, this paper concludes by raising the question whether healthcare providers should step away from catering for religious and cultural needs that do not directly affect treatment outcomes, and instead put the onus on individual communities to provide resources to meet spiritual, cultural and religious needs of patients.

Design and internal validation of an obstetric early warning score: secondary analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

We designed and internally validated an aggregate weighted early warning scoring system specific to the obstetric population that has the potential for use in the ward environment. Direct obstetric admissions from the Intensive Care National Audit and Research Centre's Case Mix Programme Database were randomly allocated to model development (n = 2240) or validation (n = 2200) sets. Physiological variables collected during the first 24 h of critical care admission were analysed. Logistic regression analysis for mortality in the model development set was initially used to create a statistically based early warning score. The statistical score was then modified to create a clinically acceptable early warning score. Important features of this clinical obstetric early warning score are that the variables are weighted according to their statistical importance, a surrogate for the FI O2 /Pa O2 relationship is included, conscious level is assessed using a simplified alert/not alert variable, and the score, trigger thresholds and response are consistent with the new non-obstetric National Early Warning Score system. The statistical and clinical early warning scores were internally validated using the validation set. The area under the receiver operating characteristic curve was 0.995 (95% CI 0.992-0.998) for the statistical score and 0.957 (95% CI 0.923-0.991) for the clinical score. Pre-existing empirically designed early warning scores were also validated in the same way for comparison. The area under the receiver operating characteristic curve was 0.955 (95% CI 0.922-0.988) for Swanton et al.'s Modified Early Obstetric Warning System, 0.937 (95% CI 0.884-0.991) for the obstetric early warning score suggested in the 2003-2005 Report on Confidential Enquiries into Maternal Deaths in the UK, and 0.973 (95% CI 0.957-0.989) for the non-obstetric National Early Warning Score. This highlights that the new clinical obstetric early warning score has an excellent ability to discriminate survivors from non-survivors in this critical care data set. Further work is needed to validate our new clinical early warning score externally in the obstetric ward environment.

Characterization of low-molecular-weight glutenin genes in Aegilops tauschii.

This paper reports the characterization of the low-molecular-weight (LMW) glutenin gene family of Aegilops tauschii (syn. Triticum tauschii), the D-genome donor of hexaploid wheat. By analysis of bacterial artificial chromosome (BAC) clones positive for hybridization with an LMW glutenin probe, seven unique LMW glutenin genes were identified. These genes were sequenced, including their untranslated 3' and 5' flanking regions. The deduced amino acid sequences of the genes revealed four putative active genes and three pseudogenes. All these genes had a very high level of similarity to LMW glutenins characterized in hexaploid wheat. The predicted molecular weights of the mature proteins were between 32.2 kDa and 39.6 kDa, and the predicted isoelectric points of the proteins were between 7.53 and 8.06. All the deduced proteins were of the LMW-m type. The organization of the seven LMW glutenin genes appears to be interspersed over at least several hundred kilo base pairs, as indicated by the presence of only one gene or pseudogene per BAC clone. Southern blot analysis of genomic DNA of Ae. tauschii and the BAC clones containing the seven LMW glutenin genes indicated that the BAC clones contained all LMW glutenin-hybridizing bands present in the genome. Two-dimensional gel electrophoresis of an LMW glutenin extract from Ae. tauschii was conducted and showed the presence of at least 11 distinct proteins. Further analysis indicated that some of the observed proteins were modified gliadins. These results suggest that the actual number of typical LMW glutenins may in fact be much lower than previously thought, with a number of modified gliadins also being present in the polymeric fraction.

Neonatal hemochromatosis, renal tubular dysgenesis, and hypocalvaria in a neonate.

We report a neonate with neonatal hemochromatosis (NH), renal tubular dysgenesis (RTD), and hypocalvaria. NH is a fatal condition of the newborn, characterized by severe idiopathic liver failure of intrauterine onset and siderosis, intra- and extrahepatic, with sparing of the reticuloendothelial system. RTD is characterized by short, abnormally developed cortical tubules that lack proximal tubule differentiation. Although both NH and RTD have been reported as entities with a genetic component, similar findings can be secondary to in utero insults. Hypocalvaria has been reported in association with fetal hypoxia including that secondary to angiotensin converting enzyme inhibitors. This 38-week-old infant died at 8.5 h. The small nodular liver weighed 44 g. Grossly, the kidneys were normal. Hypocalvaria was present. Microscopically, the hepatic parenchyma was distorted by fibrous tracts, proliferation of bile ducts, and abundant iron deposition in hepatocytes. Extrahepatic siderosis in the pancreas, myocardium, and other organs was consistent with NH. Proximal convoluted tubules were not seen on routine stains and markers for proximal tubules were negative. Previous reports have linked NH with RTD and RTD with hypocalvaria. This infant had all three of these rare conditions, which have been hypothesized or shown to be due to genetic factors, hypoxia, or drugs. The etiology in this case is unknown.

Transbronchial lung biopsy: can specimen quality be predicted at the time of biopsy?

STUDY OBJECTIVES: To determine the bronchoscopist's ability to predict specimen quality at the time of transbronchial biopsy and to determine the influence of biopsy specimen size and alveolar content on diagnostic value. DESIGN: Prospective, blinded, observational analysis. SETTING: Tertiary care academic hospital-based pulmonary practice. PATIENTS: Forty-three adult patients who underwent transbronchial lung biopsy. INTERVENTIONS: Each of 170 biopsy specimens was rated as to likelihood of containing diagnostic tissue, size and ability to float, tissue types present, number of alveoli, and pathologic diagnosis. RESULTS: Fifteen percent of biopsy specimens were small and 40% were large. Seventy-six percent of specimens floated; 61.8% of the 170 biopsy specimens contained abnormal lung tissue; and 14.7% of individual specimens were diagnostic. Fifty-two percent of specimens contained >20 alveoli. Larger biopsy specimens were more likely to contain diagnostic tissue (r=0.29, p=0.001). Cup forceps retrieved smaller pieces of tissue (p=0.007) and were less likely to obtain diagnostic tissue (p=0.06). Physician ratings of specimen quality (mean+/-SD) did not differ between specimens containing normal and abnormal tissue (5.98+/-2.3 vs 5.46+/-5.5; p=0.24) or between specimens containing diagnostic vs nondiagnostic tissue (5.56+/-2.5 vs 6.25+/-2.1; p=0.14). Specimens that floated were no more likely to be diagnostic or abnormal than specimens that sank (p<0.05). Diagnosis when established was made by the first biopsy specimen in 53.3% and the second in 33.3% CONCLUSIONS: Physician estimate of biopsy specimen quality and the float sign are not helpful in predicting that the biopsy specimen contains abnormal or diagnostic tissue. Diagnostic biopsy specimen will likely be obtained if the size of the specimen fills the forceps, 2 to 4 biopsies are performed, and toothed forceps are used.

Prenatal ultrasound diagnosis of abdominal aortic aneurysm with fibrotic occlusion in aortic branch vessels.

In a 35-year-old multiparous patient, an ultrasound scan performed at 32 weeks' gestational age for size less than dates revealed an appropriately grown fetus with a two-vessel umbilical cord. Also noted were dilated, tortuous abdominal and pelvic vessels. A scan at 33.5 weeks confirmed the two-vessel cord and noted a widely dilated abdominal aorta and a left foot 2 cm shorter than the right. Delivery at 36 weeks was followed by a neonatal course complicated by thromboses, renovascular hypertension, and a newly patent ductus with pulmonary hypertension. Successful ligation was followed by acute pulmonary hypertension, cardiac dysfunction and death. Autopsy findings included aneurysmal dilation of the abdominal aorta without evidence of arterial wall pathology.

Tissue mast cells in breast cancer.

The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p less than or equal to .05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted.

Objective pathological diagnosis of coal worker's pneumoconiosis.

Pertinent pathological features of lungs obtained at autopsies from 99 coal miners were compared with those observed in the lungs of 268 male town dwellers of comparable age who were not occupationally related to the coal mining or other industries at risk for development of pneumoconiosis. The degree of anthracotic pigment deposition and severity of type of pigmented lesion with its accompanying reticulum fiber formation and fibrosis were significantly greater in lungs of miners. There was a high degree of overlap in degree of pigment deposition, particularly those quantitated as grades 1 and 2 and in lesions regarded as types 1 and 2. The greatest divergence was observed for prevalence of nodular pulmonary lesions (type 4). There was also a considerable divergence in the type 3 alteration characterized by nonnodular aggregates of carbon-laden macrophages accompanied by minimal reactive fibrosis. It appears that an objective pathological diagnosis of coal workers' pneumoconiosis (CWP) can be rendered only by the demonstration of type 4 lesions. Approximately 25% of coal miners exhibited unequivocal features of CWP. No significant differences concerning incidence or types of emphysema or frequency of chronic cor pulmonale were encountered between the two populations.