A Propensity-Matched Cohort Study of Intravenous Iron versus Red Cell Transfusions for Preoperative Iron-Deficiency Anemia.

BACKGROUND: While preoperative anemia is associated with adverse perioperative outcomes, the benefits of treatment with iron replacement versus red blood cell (RBC) transfusion remain uncertain. We used a national database to establish trends in preoperative iron-deficiency anemia (IDA) treatment and to test the hypothesis that treatment with preoperative iron may be superior to RBC transfusion. METHODS: This study is a propensity-matched retrospective cohort analysis from 2003 to 2023 using TriNetX Research Network, which included surgical patients diagnosed with IDA within 3 months preoperatively. After matching for surgery type and comorbidities, we compared a cohort of patients with preoperative IDA who were treated with preoperative intravenous (IV) iron but not RBCs (n = 77,179), with a cohort receiving preoperative RBCs but not IV iron (n = 77,179). Propensity-score matching was performed for age, ethnicity, race, sex, overweight and obesity, type 2 diabetes, hyperlipidemia, essential hypertension, heart failure, chronic ischemic heart disease, neoplasms, hypothyroidism, chronic kidney disease, nicotine dependence, surgery type, and lab values from the day of surgery including ferritin, transferrin, and hemoglobin split into low (<7 g/dL), medium (7-<12 g/dL), and high (≥12 g/dL) to account for anemia severity. The primary outcome was 30-day postoperative mortality with the secondary outcomes being 30-day morbidity, postoperative hemoglobin level, and 30-day postoperative RBC transfusion. RESULTS: Compared with RBC transfusion, preoperative IV iron was associated with lower risk of postoperative mortality (n = 2550/77,179 [3.3%] vs n = 4042/77,179 [5.2%]; relative risk [RR], 0.63, 95% confidence interval [CI], 0.60-0.66), and a lower risk of postoperative composite morbidity (n = 14,174/77,179 [18.4%] vs n = 18,632/77,179 [24.1%]; RR, 0.76, 95% CI, 0.75-0.78) (both P = .001 after Bonferroni adjustment). Compared with RBC transfusion, IV iron was also associated with a higher hemoglobin in the 30-day postoperative period (10.1 ± 1.8 g/dL vs 9.4 ± 1.7 g/dL, P = .001 after Bonferroni adjustment) and a reduced incidence of postoperative RBC transfusion (n = 3773/77,179 [4.9%] vs n = 12,629/77,179 [16.4%]; RR, 0.30, 95% CI, 0.29-0.31). CONCLUSIONS: In a risk-adjusted analysis, preoperative IDA treatment with IV iron compared to RBC transfusion was associated with a reduction in 30-day postoperative mortality and morbidity, a higher 30-day postoperative hemoglobin level, and reduced postoperative RBC transfusion. This evidence represents a promising opportunity to improve patient outcomes and reduce blood transfusions and their associated risk and costs.

Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

INTRODUCTION: Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. METHODS: A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. RESULTS: A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. CONCLUSION: Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

How do we ensure a safe ABO recheck process?

BACKGROUND: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples. MATERIALS AND METHODS: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided. RESULTS: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected. CONCLUSION: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices.

Therapeutic plasma exchange for the treatment of refractory necrotizing autoimmune myopathy.

INTRODUCTION: Necrotizing autoimmune myopathy (NAM) is strongly associated with pathognomonic autoantibodies targeting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or signal recognition particle (SRP), whose levels in turn are correlated with serum creatine kinase (CK) and necrosis. Thus, NAM may be amenable to therapeutic plasma exchange (TPE) to remove pathogenic antibodies and improve patient symptoms. METHODS: A retrospective case series and literature review of patients presenting with NAM and undergoing treatment with TPE was performed. Clinical data including patient demographics, symptoms, physical exam findings, muscle biopsy, lower extremity imaging, prior therapy, and duration from diagnosis to TPE initiation were collected retrospectively for adult patients with NAM treated with TPE after failing to respond to immunomodulatory therapy. Laboratory data including change in CK levels and myositis-specific antibody titers from baseline were measured in some patients. RESULTS: Six patients (median age at diagnosis 52.5 years, interquartile range [IQR] 35.8-64.5 years, four male/two female) underwent a median of 7.5 (IQR: 5-10) TPE procedures with 5% albumin as replacement. All patients exhibited a statistically significant reduction in CK level from pre-TPE baseline (range: 43.0%-58.7% reduction). Responses in this cohort were best in patients with antibodies targeting HMGCR and SRP, which are most strongly associated with NAM. These results compare favorably to a literature review of NAM patients (n = 19) treated with TPE, who also exhibited positive clinical and laboratory responses across varying treatment lengths. CONCLUSION: TPE can play a role in the management of NAM, particularly in patients with HMGCR or SRP antibodies who are refractory to pharmacologic immunosuppression.

Transfusion support and alternatives for Jehovah's Witness patients.

PURPOSE OF REVIEW: Jehovah's Witness patients with critical anemia or undergoing major surgery are challenging for healthcare providers to manage, as most will decline transfusion of whole blood and its main components. Recent advances in our understanding of hemostatic agents, alternative hemoglobin-based oxygen carriers, and patient blood management have culminated in a complex array of options to manage critical anemia and bleeding in this patient population. RECENT FINDINGS: Refusal of blood products in the setting of critical anemia is associated with significant risk of morbidity and mortality. With implementation of patient blood management measures, targeted treatment of anemia and coagulopathy has reduced the need for transfusions. Likewise, increased clinical experience with hemoglobin-based oxygen carriers in Jehovah's Witnesses with critical anemia has provided new insights into their potential benefits and pitfalls. SUMMARY: Options and alternatives to manage the Jehovah's Witness patient in the perioperative setting or in the setting of critical anemia will be reviewed.

Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing.

Results of DNA mismatch repair testing are used to detect Lynch syndrome and have prognostic and therapeutic implications among patients with sporadic colorectal carcinomas. Immunohistochemistry for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6) and PCR for microsatellite instability are two established methods for assessing mismatch repair function. Older literature suggested a discordance rate of approximately 5% between these assays, leading some institutions to perform dual testing on all cases. Although universal mismatch repair testing is now recommended by multiple professional organizations, none provide guidelines regarding preferred assays. We surveyed 96 academic and nonacademic institutions to assess Lynch syndrome screening practices and evaluated discordance rates between immunohistochemistry and PCR among 809 colorectal cancers tested in our own institution. Our survey demonstrated no significant differences between academic and nonacademic practices with respect to testing strategies. Eighty six percent performed universal screening, and usually (76%) employed immunohistochemistry on initial biopsy samples. Only 20% employed PCR; these were mostly academic practices that used both immunohistochemistry and PCR (p < 0.01 compared with the nonacademic groups). Loss of MLH1/PMS2 staining was often (90%) followed by either BRAF mutational analysis or MLH1 methylation assays. Only 24% adhered to WHO recommendations to assign histologic grade based on mismatch repair status. We found only 3 cases (0.4%) with discordant immunohistochemistry and PCR results in our own practice: 1 reflected decreased MSH-6 staining in a neoadjuvantly treated microsatellite stable tumor, 1 MLH1-deficient tumor showed diminished MLH1/PMS2 in the tumor compared with internal control, and 1 case reflected an error in the molecular laboratory. Overall, our results showed extremely low discordance between methods assessing mismatch repair status and would suggest immunohistochemistry as the preferred single screening test. PCR can be reserved for cases that show equivocal immunostaining patterns.

Detecting senescence: methods and approaches.

The detection of senescent cells has become an important area of research in the aging field. Due to the complexity of the senescence program and the lack of a unique signature for senescence, the detection of these cells remains problematic. This is especially true for in vivo detection in aged or diseased tissue samples. This chapter outlines approaches for the detection of senescent cells based upon methods established for mesenchymal cells in culture. A stepwise approach to the detection of senescent cells using multiple techniques is provided.

Effectiveness of quadrivalent human papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia.

OBJECTIVE: To measure the effectiveness of the quadrivalent human papillomavirus (HPV) vaccine against cervical abnormalities four years after implementation of a nationally funded vaccination programme in Queensland, Australia. DESIGN: Case-control analysis of linked administrative health datasets. SETTING: Queensland, Australia. PARTICIPANTS: Women eligible for free vaccination (aged 12-26 years in 2007) and attending for their first cervical smear test between April 2007 and March 2011. High grade cases were women with histologically confirmed high grade cervical abnormalities (n = 1062) and "other cases" were women with any other abnormality at cytology or histology (n = 10,887). Controls were women with normal cytology (n = 96,404). MAIN OUTCOME MEASURES: Exposure odds ratio (ratio of odds of antecedent vaccination (one, two, or three vaccine doses compared with no doses) among cases compared with controls), vaccine effectiveness ((1-adjusted odds ratio) × 100), and number needed to vaccinate to prevent one cervical abnormality at first screening round. We stratified by four age groups adjusted for follow-up time, year of birth, and measures of socioeconomic status and remoteness. The primary analysis concerned women whose first ever smear test defined their status as a case or a control. RESULTS: The adjusted odds ratio for exposure to three doses of HPV vaccine compared with no vaccine was 0.54 (95% confidence interval 0.43 to 0.67) for high grade cases and 0.66 (0.62 to 0.70) for other cases compared with controls with normal cytology, equating to vaccine effectiveness of 46% and 34%, respectively. The adjusted numbers needed to vaccinate were 125 (95% confidence interval 97 to 174) and 22 (19 to 25), respectively. The adjusted exposure odds ratios for two vaccine doses were 0.79 (95% confidence interval 0.64 to 0.98) for high grade cases and 0.79 (0.74 to 0.85) for other cases, equating to vaccine effectiveness of 21%. CONCLUSION: The quadrivalent HPV vaccine conferred statistically significant protection against cervical abnormalities in young women who had not started screening before the implementation of the vaccination programme in Queensland, Australia.

Reducing all-cause mortality among patients with psychiatric disorders: a population-based study.

BACKGROUND: Among patients with psychiatric disorders, there are 10 times as many preventable deaths from physical disorders as there are from suicide. We investigated whether compulsory community treatment, such as community treatment orders, could reduce all-cause mortality among patients with psychiatric disorders. METHODS: We conducted a population-based survival analysis of an inception cohort using record linking. The study period extended from November 1997 to December 2008. The cohort included patients from all community-based and inpatient psychiatric services in Western Australia (state population 1.8 million). We used a 2-stage design of matching and Cox regression to adjust for demographic characteristics, previous use of health services, diagnosis and length of psychiatric history. We collected data on successive cohorts for each year for which community treatment orders were used to measure changes in numbers of patients, their characteristics and outcomes. Our primary outcome was 2-year all-cause mortality. Our secondary outcomes were 1-and 3-year all-cause mortality. RESULTS: The study population included 2958 patients with community treatment orders (cases) and 2958 matched controls (i.e., patients with psychiatric disorders who had not received a community treatment order). The average age for cases and controls was 36.7 years, and 63.7% (3771) of participants were men. Schizophrenia and other nonaffective psychoses were the most common diagnoses (73.4%) among participants. A total of 492 patients (8.3%) died during the study. Cox regression showed that, compared with controls, patients with community treatment orders had significantly lower all-cause mortality at 1, 2 and 3 years, with an adjusted hazard ratio of 0.62 (95% confidence interval 0.45-0.86) at 2 years. The greatest effect was on death from physical illnesses such as cancer, cardiovascular disease or diseases of the central nervous system. This association disappeared when we adjusted for increased outpatient and community contacts with psychiatric services. INTERPRETATION: Community treatment orders might reduce mortality among patients with psychiatric disorders. This may be partly explained by increased contact with health services in the community. However, the effects of uncontrolled confounders cannot be excluded.

Cancer-related mortality in people with mental illness.

CONTEXT There is a 30% higher case fatality rate from cancer in psychiatric patients even though their incidence of cancer is no greater than in the general population. The reasons are unclear, but if increased cancer mortality were due to lifestyle only, cancer incidence should be similarly increased. Other hypotheses include delays in presentation, leading to more advanced staging at diagnosis, and difficulties in treatment access following diagnosis. OBJECTIVE To assess why psychiatric patients are no more likely than the general population to develop cancer but are more likely to die of it. DESIGN, SETTING, AND PATIENTS A population-based record-linkage analysis compared psychiatric patients with the Western Australian population, using an inception cohort to calculate rates and hazard ratios. Mental health records were linked with cancer registrations and death records from January 1, 1988, to December 31, 2007, in Western Australia. MAIN OUTCOME MEASURES Metastases, incidence, mortality, and access to cancer interventions. RESULTS There were 6586 new cancers in psychiatric patients. Cancer incidence was lower in psychiatric patients than in the general population in both males (rate ratio = 0.86; 95% CI, 0.82-0.90) and females (rate ratio = 0.92; 95% CI, 0.88-0.96), although mortality was higher (males: rate ratio = 1.52; 95% CI, 1.45-1.60; females: rate ratio = 1.29; 95% CI, 1.22-1.36). The proportion of cancer with metastases at presentation was significantly higher in psychiatric patients (7.1%; 95% CI, 6.5%-7.8%) than in the general population (6.1%; 95% CI, 6.0%-6.2%). Psychiatric patients had a reduced likelihood of surgery (hazard ratio = 0.81; 95% CI, 0.76-0.86), especially resection of colorectal, breast, and cervical cancers. They also received significantly less radiotherapy for breast, colorectal, and uterine cancers and fewer chemotherapy sessions. CONCLUSIONS Although incidence is no higher than in the general population, psychiatric patients are more likely to have metastases at diagnosis and less likely to receive specialized interventions. This may explain their greater case fatality and highlights the need for improved cancer screening and detection.

Astrocyte senescence as a component of Alzheimer's disease.

Aging is the main risk factor for Alzheimer's disease (AD); however, the aspects of the aging process that predispose the brain to the development of AD are largely unknown. Astrocytes perform a myriad of functions in the central nervous system to maintain homeostasis and support neuronal function. In vitro, human astrocytes are highly sensitive to oxidative stress and trigger a senescence program when faced with multiple types of stress. In order to determine whether senescent astrocytes appear in vivo, brain tissue from aged individuals and patients with AD was examined for the presence of senescent astrocytes using p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of senescence. Compared with fetal tissue samples (n = 4), a significant increase in p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n = 6; P = 0.02) and 78 to 90 years (n = 11; P<10(-6)). In addition, the frontal cortex of AD patients (n = 15) harbored a significantly greater burden of p16(INK4a)-positive astrocytes compared with non-AD adult control subjects of similar ages (n = 25; P = 0.02) and fetal controls (n = 4; P<10(-7)). Consistent with the senescent nature of the p16(INK4a)-positive astrocytes, increased metalloproteinase MMP-1 correlated with p16(INK4a). In vitro, beta-amyloid 1-42 (Aß(1-42)) triggered senescence, driving the expression of p16(INK4a) and senescence-associated beta-galactosidase. In addition, we found that senescent astrocytes produce a number of inflammatory cytokines including interleukin-6 (IL-6), which seems to be regulated by p38MAPK. We propose that an accumulation of p16(INK4a)-positive senescent astrocytes may link increased age and increased risk for sporadic AD.