Severe Morbidity Research Articles

Risk factors for postoperative acute kidney injury after radical cystectomy for bladder cancer in the era of ERAS protocols: A retrospective observational study.

Radical cystectomy (RC) is a major surgery associated with a high morbidity rate. Perioperative fluid management according to enhanced recovery after surgery (ERAS) protocols aims to maintain patients in an optimal euvolemic state while exposing them to acute kidney injury (AKI) in the event of hypovolemia. Postoperative AKI is associated with severe morbidity and mortality. Our main objective was to determine the association between perioperative variables, including some component of ERAS protocols, and occurrence of postoperative AKI within the first 30 days following RC in patients presenting bladder cancer. Our secondary objective was to evaluate the association between a postoperative AKI and the occurrence or worsening of a chronic kidney disease (CKD) within the 2 years following RC. We conducted a retrospective observational study in a referral cancer center in France on 122 patients who underwent an elective RC for bladder cancer from 01/02/2015 to 30/09/2019. The primary endpoint was occurrence of AKI between surgery and day 30. The secondary endpoint was survival without occurrence or worsening of a postoperative CKD. AKI and CKD were defined by KDIGO (Kidney Disease: Improving Global Outcomes) classification. Logistic regression analyse was used to determine independent factors associated with postoperative AKI. Fine and Gray model was used to determine independent factors associated with postoperative CKD. The incidence of postoperative AKI was 58,2% (n = 71). Multivariate analysis showed 5 factors independently associated with postoperative AKI: intraoperative restrictive vascular filling < 5ml/kg/h (OR = 4.39, 95%CI (1.05-18.39), p = 0.043), postoperative sepsis (OR = 4.61, 95%CI (1.05-20.28), p = 0.043), female sex (OR = 0.11, 95%CI (0.02-0.73), p = 0.022), score SOFA (Sequential Organ Failure Assessment) at day 1 (OR = 2.19, 95%CI (1.15-4.19), p = 0.018) and delta serum creatinine D1 (OR = 1.06, 95%CI (1.02-1.11), p = 0.006). During the entire follow-up, occurrence or worsening of CKD was diagnosed in 36 (29.5%). A postoperative, AKI was strongly associated with occurrence or worsening of a CKD within the 2 years following RC even after adjustment for confounding factors (sHR = 2.247, 95%CI [1.051-4.806, p = 0.037]). A restrictive intraoperative vascular filling < 5ml/kg/h was strongly and independently associated with the occurrence of postoperative AKI after RC in cancer bladder patients. In this context, postoperative AKI was strongly associated with the occurrence or worsening of CKD within the 2 years following RC. A personalized perioperative fluid management strategy needs to be evaluated in these high-risk patients.

Severe maternal morbidity in high income countries

IntroductionWith declining maternal mortality rates in high income countries (HICs), severe maternal morbidity (SMM) is becoming an important quality measure of maternal care. However, there is no international consensus on the definition and types of SMM. This study aims to critically analyze published literature on SMM in HICs. ObjectivesTo compare definitions and criteria used to identify SMM, and to identify the main types and risk factors contributing to SMM in eight HICs. MethodsThree databases were searched, results were filtered, and ten studies were critically appraised. ResultsSix of the articles discussed SMM identification criteria and proposed definition modifications. Longer hospital stay and admission to intensive care unit were suggested as additional criteria. Disease-based criteria was shown to be superior to organ dysfunction criteria. Seven articles detailed common types of SMM as severe haemorrhage, hypertensive disorders, and pre-eclampsia/eclampsia. Six articles described SMM risk factors, of which advanced maternal age and caesarean delivery were most common. DiscussionThis literature review identified disease-based criteria and Canadian study criteria as promising measures of SMM. It also identified several types and risk factors of SMM common between HICs. These findings can help physicians identify women at risk of SMM. The study is however limited to eight HICs and ten studies. Further research should aim to investigate how the measures compare with previous sources of criteria, and to discern the association of weight and race risk factors with SMM.

Postpartum Management of Hypertensive Disorders of Pregnancy in Six Large U.S. Hospital Systems: Descriptive Review and Identification of Clinical and Research Gaps.

Hypertensive disorders of pregnancy (HDPs) are a key contributor to maternal morbidity and mortality. Several gaps in knowledge remain regarding best practices in the postpartum management of HDPs. In this review, we describe postpartum HDPs management among six large academic U.S. hospital systems: Medical College of Wisconsin, University of Pittsburgh, University of Wisconsin-Madison, Northwestern University, University of Minnesota, and Boston Medical Center. We identified that all six health systems discharge patients with HDPs diagnosed with a blood pressure (BP) cuff and use the same two antihypertensive medications, nifedipine and labetalol, as first- and second-line treatment of HDPs. Northwestern University routinely adds oral furosemide for 5 days for patients with BP that exceeds 150/100 mm Hg. Most hospital systems administer magnesium sulfate routinely when readmission for HDPs occurs. In contrast, there was variation in BP threshold for antihypertensive treatment initiation, use of remote BP monitoring program, use of a transition clinic, delivery or lack of education on long-term cardiovascular disease risk, and BP management through the first 6 weeks postpartum and beyond. Based on the clinical review, we identified clinical gaps and formulated considerations for research priorities in the field of postpartum HDPs management. KEY POINTS: · Several gaps in knowledge remain regarding best practices in postpartum management of HDPs.. · There is a variation in the BP threshold for antihypertensive treatment initiation.. · Data are lacking on the reduction in severe maternal morbidity (SMM) and racial disparities in SMM with remote monitoring..

Hereditary Hemorrhagic Telangiectasia: Pregnancy and Delivery-Specific Considerations and Outcomes.

Prior studies have evaluated maternal outcomes in patients with hereditary hemorrhagic telangiectasia (HHT), yet pregnancy- and delivery-specific data remain limited. This study aims to evaluate pregnancy and delivery outcomes in patients with HHT. This retrospective cohort study used the Nationwide Readmissions Database to identify patients with HHT diagnosis on delivery between 2010 and 2021. The primary outcome was severe maternal morbidity (SMM). Secondary outcomes included nontransfusion SMM, preterm birth, stillbirth, prelabor rupture of membranes or preterm prelabor rupture of membranes, cesarean delivery, respiratory bleeding, cerebrovascular complications, patient disposition, and length of stay. Trends in the prevalence of HHT at delivery were assessed with logistic regression. Logistic regression analyses, adjusting for age, payer, zip code income, hospital size, and teaching status, were also used to produce adjusted relationships between HHT status and outcomes. The cohort of 21,698,861 delivered pregnancies corresponded to a national estimate of 44,325,599. Of those, 612 (national estimate: 1,265; 2.8 per 100,000) had a diagnosis of HHT. A steady rise in the HHT diagnosis rate during pregnancy from 2010 to 2021 (1.7 per 100,000 in 2010, 3.8 per 100,000 in 2021, p < 0.001 for trend) was seen. Patients with HHT were significantly more likely to experience SMM compared with patients without HHT (7.8 vs. 1.7%, adjusted relative risk [aRR]: 4.49 [95% confidence interval, CI: 3.06, 6.58]). Rates of preterm birth (14.2 vs. 8.5%, aRR: 1.57 [95% CI: 1.22, 2.03]), cesarean delivery (41.0 vs. 32.9%, aRR: 1.23 [95% CI: 1.07, 1.41]), respiratory bleeding (2.1 vs. <0.1%, aRR: 94.44 [56.64, 157.46]), and cerebrovascular complications (0.9 vs. <0.1%, aRR: 22.89 [9.89, 52.96]) were higher in patients with HHT than non-HHT patients. There was no difference in stillbirth rates between groups. Patients with HHT have higher rates of SMM and adverse delivery outcomes when compared with the baseline population. · There was a steady rise in the rates of HHT during pregnancy from 2010 to 2021.. · Patients with HHT are more likely to experience SMM.. · Patients with HHT are more likely to have a preterm delivery and cesarean delivery..

Maternal cigarette smoking before or during pregnancy increases the risk of severe neonatal morbidity after delivery: a nationwide population-based retrospective cohort study

BackgroundThe association of maternal cigarette smoking during pregnancy with severe neonatal morbidity (SNM) is still inconclusive. We aimed to examine the associations of the timing and the intensity of maternal...

Novel Approach to Identify Severe Maternal Morbidity Clusters: A Latent Class Analysis.

Whether clusters exist within severe maternal morbidity (SMM), a set of life-threatening heterogeneous conditions, is not known. Our primary objective was to identify SMM clusters using a data-driven clustering technique, their associated predictors and outcomes. From 2008 to 2017, we used a delivery database supplemented by state data and medical record abstraction from a single institution in Pennsylvania. To identify SMM clusters, we applied latent class modeling that included 23 conditions defined by 21 Centers for Disease Control SMM indicators, intensive care unit (ICU) admission, or prolonged postpartum length of stay. Logistic regression models estimated risk for SMM clusters and associations between clusters and maternal and neonatal outcomes. Among 97,492 deliveries, 2.7% (N = 2,666) experienced SMM by any of the 23 conditions. Four clusters were identified as archetypes of SMM. Deliveries labeled as Hemorrhage (37.7%, N = 1,004) were characterized by blood transfusions and sickle cell anemia; Critical Care (28.1%, N = 748) by ICU admission and amniotic embolism; Vascular (24.5%, N = 654) by cerebrovascular conditions; and Shock (9.8%, N = 260) by ventilatory support and shock. Hypertensive disorders of pregnancy, depression, and Medicaid insurance were associated with Shock cluster. People in all clusters had a high risk of maternal death within 1 year (odds ratio: 12.0, 95% confidence interval: 6.2-23). Infants born to those in the shock cluster had the highest odds of neonatal death, low Apgar scores, and neonatal ICU admission. We identified four novel SMM clusters that may help understand the collection of conditions defining SMM, underlying pathways and the importance of comorbidities such as depression and social determinants of health markers that amplify the well-established risk factors for SMM such as hypertensive disorders of pregnancy. · A total of 2.7% of deliveries experienced SMM events.. · There are four distinct SMM clusters: Hemorrhage, Critical Care, Vascular, and Shock.. · Not all SMM clusters bear the same risk for adverse perinatal outcomes..

Maternal and obstetric outcomes in women with pregnancy-associated haematological malignancies: an observational nationwide cohort study

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies. We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32-36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category). Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62-1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07-4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12-2·38], p=0·40), and acute leukaemia alone (0·84 [0·50-1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72-29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91-17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34-14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group. This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively. None. For the French translation of the abstract see Supplementary Materials section.

Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, we identify the upregulation of SLC39A5 and associated transcription factor KLF5 in biopsied intestinal tissue specimens from patients with SBS. Thus, we identify zinc supplementation as a potential therapy for SBS and describe a xenotransplantation model that provides a platform for discovery in other intestinal diseases.

8574 Single cell multiomics suggests tumor cell energy metabolism heterogeneity in non-functioning gonadotroph pituitary adenomas

Abstract Disclosure: F.M. Ruf-Zamojski: None. Z. Zhang: None. W. Cheng: None. G.R. Smith: None. M. Zamojski: None. N. Mendelev: None. Y. Ge: None. D. Marrero-Rodríguez: None. K. Taniguchi-Ponciano: None. C.L. Andoniadou: None. E. Zaslavsky: None. X. Chen: None. O.G. Troyanskaya: None. M. Mercado: None. S.C. Sealfon: None. Pituitary adenomas cause hormonal dysregulation and severe morbidity. The absence of clear biomarkers for prognosis/treatment and the high risk of recurrence make management challenging. Non-functioning gonadotroph pituitary adenomas (NFPAs) represent proliferation of gonadotroph lineage cells without an increase in secretion of gonadotropins. Detection is often delayed until mass effects cause visual defects. Higher resolution molecular study may improve classification, diagnosis, treatment, and provide insight into adenoma biology. We analyzed four NFPAs using unbiased genome-wide same-cell single nucleus 10X Genomics multiome assay (transcriptome and chromatin accessibility) to define individual cell identity/states in comparison with normal gonadotrope cell references from twelve age/sex-matched human post-mortem pituitaries. In total, we generated high quality multiomics single-cell data for 33,832 adenoma cells and 5,451 normal gonadotropes. We identified tumor, immune, vascular, and proliferative cells confirming cellular heterogeneity. Multidimensional scaling analysis using Manhattan distances between cell types showed that NFPA gonadotropes were closer in gene expression to healthy gonadotropes among all pituitary cell types. In addition, we observed differences in the macrophage and endothelial cell populations between tumors and healthy pituitaries. Next, we studied gene regulatory circuitry (regulated gene, modulating transcription factor and its chromatin interaction site) using the new Control of Regulation Extracted from Multiomics Assays (CREMA, [1]) multiome analysis method which showed high variation between normal and tumor gonadotropes. Within each adenoma, the NFPA tumor cells encompassed two main subgroups of cells, one group (GT+ marker tumor cells) expressing established gonadotrope markers and another group not (GT- marker tumor cells). GT+ and GT- tumor cells formed a cluster distinct from healthy gonadotropes. GT+ and GT- tumor cells differed by their level of expression of mitochondrial genes, suggesting decreased aerobic capacity associated with the GT- tumor subgroup. Interestingly, differential analyses between the healthy and the NFPA gonadotropes from same-cell multiome data highlighted dissimilar gene expression and chromatin accessibility patterns.Our newly collected single cell data characterize the difference between NFPA tumor cells and normal gonadotrope cells. Our results suggest a Warburg-effect like difference in aerobic respiratory capacity among tumor cells within the same pituitary adenoma. Overall, this study brings new insights into the molecular characteristics of NFPAs, including tumor cell heterogeneity, and represents a new resource for the field. [1] PMID: 38084892. Presentation: 6/1/2024

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of &amp;gt;1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

Recurrence of Severe Maternal Morbidity and Transfusion During Delivery Hospitalisations: A Retrospective Cohort Study.

To determine risks for non-transfusion severe maternal morbidity and transfusion during a second delivery hospitalisation based on clinical risk factors and obstetric complications from an index, first delivery hospitalisation. Retrospective cohort. Delivery hospitalisations in the 2010-2017 New York State Inpatient Database. Patients with a first index delivery hospitalisation followed by a second delivery hospitalisation during the study period were included. Clinical risk factors and obstetric complications were obtained from the first index delivery hospitalisation. Adjusted logistic regression models for non-transfusion severe maternal morbidity during the second delivery were performed with adjusted (aORs) odds ratios as measures of effect. These analyses were then repeated for the outcome of transfusion. Of 624 500 paired delivery hospitalisations to 312 250 women, severe maternal morbidity occurred among 0.85% of second deliveries (n = 2672). When adjusted analysis was performed, several clinical factors were associated with severe maternal morbidity in a subsequent pregnancy, including severe maternal morbidity during the index pregnancy (aOR 8.4, 95% CI 7.0, 9.9), transfusion (aOR 2.0, 95% CI 1.6, 2.4) and pregestational diabetes (aOR 2.2, 95% 1.6, 2.9). When analyses were repeated for transfusion, several factors were associated with increased risk, including severe maternal morbidity (aOR 1.5, 95% CI 1.2, 1.8), index transfusion (aOR 6.3, 95% CI 5.6, 7.0), chronic heart disease (aOR 1.6, 95% 1.4, 1.9) and pregestational diabetes (aOR 1.7, 95% 1.3, 2.2). Many obstetric complications and chronic conditions identified during an index delivery hospitalisation are associated with severe morbidity during a second, subsequent delivery. Index severe maternal morbidity is associated with the highest odds. These findings may be of use in patient counselling and risk stratification.

Examining associations between social vulnerability and maternal morbidity among a multicentre cohort of pregnancies complicated by placenta accreta spectrum disorder in New York City

BackgroundPlacenta accreta spectrum (PAS) disorder is a source of severe obstetric morbidity and mortality worldwide. The objective of this paper was to evaluate the potential relationship between social vulnerability and...

Cancer diagnosis during pregnancy is associated with severe maternal and neonatal morbidity

BackgroundData on maternal and fetal outcomes in patients diagnosed with cancer during pregnancy are limited. Given expected increase in patients diagnosed with cancer during pregnancy, there is a growing need to evaluate clinical outcomes. ObjectiveTo evaluate obstetric outcomes among women with early-stage gynecologic or breast cancer who were diagnosed during pregnancy compared to women without cancer in a population-based cohort. MethodsWe performed a population-based study of women aged 18-45 years with stage I gynecologic or stage I-III breast cancer reported to the California Cancer Registry for the years 2000-2012. Data were linked to the 2000-2012 California birth data to produce a database with cancer characteristics and obstetric outcomes. We included patients who had a delivery within the 10 months following cancer diagnosis. The primary outcome was severe maternal morbidity (SMM). Secondary outcomes included pre-term birth (PTB) and neonatal morbidity. Propensity scores were used to match similar controls to cases in a 2:1 ratio based on demographic attributes and medical comorbidities included in the Obstetric Comorbidity Index (OB-CMI). Logistic regressions were used to evaluate outcomes. ResultsThe cohort consisted of 503 women with cancer in pregnancy (319 breast, 125 ovarian, 59 cervical), and 1,006 matched controls. Cancer during pregnancy was associated with higher odds of SMM (6.8% vs <1.1%; odds ratio [OR] 8.03, 95% CI 3.82-16.88), PTB between 32-36 weeks (32.6% vs 8.3%, OR 5.38, 95% CI 4.02-7.20), and neonatal morbidity (12.5% vs 6.1%; OR 2.22, 95% CI 1.53-3.21) compared to matched controls. In sub-analysis of SMM indicators, hysterectomy and sepsis were significantly associated with cancer during pregnancy (4.8% vs <1.1%, P<.001; <2.2% vs 0.0%, P=.037, respectively). ConclusionCancer during pregnancy is associated with increased risk of maternal and neonatal morbidity. These findings highlight the need for careful management and consideration of obstetric outcomes in these patients.

Hypertensive Disorders and Cardiovascular Severe Maternal Morbidity in the US, 2015-2019

The incidence of severe maternal morbidity (SMM)-and particularly cardiovascular SMM (cvSMM), the first cause of pregnancy-related mortality-has been rising in North America. Although hypertensive disorders of pregnancy (HDP) are common, their association with cvSMM specifically remains unclear. To assess the association between individual subtypes of HDP and cvSMM, in addition to overall SMM, in a large, nationally representative sample. A population-based cohort study using the United States National Inpatient Sample was conducted. Individuals with obstetric deliveries between 2015 and 2019 were included. Data analysis was performed from October 2023 to February 2024. HDP subtypes included gestational hypertension, chronic hypertension, preeclampsia without severe features, severe preeclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelet) syndrome. The primary outcome was a composite of cvSMM (including conditions such as pulmonary edema, stroke, and acute myocardial infarction) and the secondary outcome was a composite of overall SMM (including cvSMM and other conditions such as respiratory failure, severe postpartum hemorrhage, and sepsis). Adjusted risk ratios (aRRs) for the association between HDP subtypes and the outcomes were estimated using modified Poisson regression models adjusted for demographic and clinical characteristics. Among 15 714 940 obstetric deliveries, 2 045 089 (13.02%) had HDP, 23 445 (0.15%) were affected by cvSMM, and 282 160 (1.80%) were affected by SMM. The mean (SD) age of the cohort was of 29 (6) years. The incidence of cvSMM was higher in participants with HDP than those without HDP (0.48% [9770 of 2 045 089] vs 0.10% [13 680 of 13 669 851]; P < .001). Participants with HELLP syndrome had the highest risk for cvSMM (aRR, 17.55 [95% CI, 14.67-21.01]), followed by severe preeclampsia (aRR, 9.11 [95% CI, 8.26-10.04]), and chronic hypertension (aRR, 3.57 [95% CI, 3.15-4.05]). Although HDP subtypes were also associated with overall SMM, the association with HELLP syndrome (aRR, 9.94 [95% CI, 9.44-10.45]), severe preeclampsia (aRR, 3.66 [95% CI, 3.55-3.78]), and chronic hypertension (aRR, 1.96 [95% CI, 1.88-2.03]) was attenuated compared with cvSMM. In this cohort study, a graded relationship by severity characterized the association between HDP and cvSMM. Although all HDP subtypes were associated with an increased risk of overall SMM, the risk was more pronounced for cvSMM.

Trends in severe maternal morbidity following an institutional team goal strategy for disparity reduction

BackgroundRacial disparities in maternal pregnancy outcomes, specifically in morbidity and mortality, are persistent in the U.S., and a multifaceted approach to mitigating these disparate outcomes is critical. In 2020, our health system committed to reducing severe maternal morbidity (SMM) in Black patients, employing multiple strategic interventions including implicit bias training, regular reporting of a composite SMM metric stratified by race and ethnicity, standardization of best practices, focused efforts for hemorrhage risk reduction, and system-wide team building. ObjectiveThe goal of this study is to investigate trends in SMM by race across this period of concentrated interventions to improve maternal outcomes overall, and specifically for Black patients. Study DesignThis is a retrospective cohort study evaluating all delivery admissions at an academic, urban, tertiary-care hospital in Philadelphia—one site of a health system encompassing five delivery hospitals—over a 3-year period from 2019 to 2021. Data including patient demographics, clinical features, and outcomes were extracted from the electronic medical record (EMR). Self-reported race was categorized as Black vs non-Black as documented in the EMR. SMM was defined according to established CDC indicators as well as additional codes identified by Vizient for common sources of SMM including hemorrhage, infection, and embolism. Data were analyzed by year with a multivariable logistic regression model including insurance type and obstetric comorbidity index (OB-CMI), a weighted scoring system accounting for numerous chronic medical conditions and antepartum pregnancy complications. ResultsIn total, 12,339 deliveries were included, 64.6% (N=8012) of which were to Black patients. Median OB-CMI score was higher for Black patients at 3 (interquartile range [IQR] 1–5) compared to 2 (IQR 1–4) for non-Black patients, P<.01. There was a significant decrease in SMM for the entire cohort over the study period (8.5% in 2019 to 6.5% in 2021, P=.001), driven by a decreased rate specifically among Black patients (8.9% in 2019 to 6.6% in 2021, P=.005) with a nonsignificant decrease for non-Black patients (7.8% in 2019 to 6.3% in 2021, P=.21). The adjusted model similarly demonstrated decreased risk of SMM over time for Black patients (2020 vs 2019 adjusted odds ratio [aOR] = 0.81, 95% confidence interval [CI] 0.69–0.96; 2021 vs 2019 aOR 0.73, 95% CI 0.62–0.86). ConclusionDedicated efforts to improve equity in maternal outcomes over a 2-year period (2020–2021) in this hospital serving a Black patient majority were associated with a significant decline in SMM, especially among Black patients. This finding demonstrates the success of a high-level, coordinated, and systematic approach in reducing SMM and associated disparities, and is highly consequential in light of the ongoing major epidemic of racial disparities in obstetric outcomes.

In vitro selection of human cerebrospinal fluid-specific aptamers using clinical samples.

Cerebrospinal fluid (CSF) leaks may occur due to numerous etiologies and are associated with severe morbidity. Currently in the U.S., confirming the presence of a CSF leak requires protein electrophoresis testing, oftentimes involving specialized processing, and there exists no point-of-care (POC) device for CSF detection. We aimed to discover a single-stranded deoxyribonucleic acid (ssDNA) aptamer capable of selectively binding to CSF-specific biomarkers, with the future goal of developing an aptamer-based POC CSF detection device. To identify a candidate aptamer, we performed Systematic Evolution of Ligands by EXponential enrichment (SELEX) using a DNA library containing a randomized 63-nucleotide (nt) stretch flanked by 2 primer-binding sites. Quantitative polymerase chain reaction (qPCR) and fluorescence anisotropy (FA) assessed aptamer binding affinity and kinetics. Following 14 SELEX cycles, 2 dominant and functionally viable 98-nt ssDNA sequences (C2 and C3) were found. C2 and C3 demonstrated ~586x and ~82x higher affinity for CSF compared to serum, respectively. Increases in FA upon aptamer exposure to higher CSF concentrations demonstrated a K1⁄2 of 5.0% and 14.1% for C2 and C3, respectively. In vitro selection of a diverse pool of ssDNA sequences yielded 2 aptamers with high selectivity for CSF-specific biomarkers, with potential for integration into a rapid POC electrochemical diagnostic system.

Elimination of schistosomiasis mekongi in reach for Lao PDR: The last patient with severe disease?

Schistosomiasis mekongi is endemic in a restricted area in Northern Cambodia and the Southern Lao People's Democratic Republic. Severe hepatobiliary morbidity is associated with chronic untreated S. mekongi infection. Since the 1980s extensive control efforts have been employed in endemic areas, resulting in substantial reduction of infection rates and disease burden. We report on a patient with a fatal course of clinically-assessed chronic schistosomiasis. This report underscores that patients with severe chronic Mekong schistosomiasis may still exist and may need treatment support.

HELLP syndrome and associated factors among pregnant women with preeclampsia/eclampsia at a referral hospital in southwestern Uganda: a cross-sectional study

BackgroundHemolysis Elevated Liver Enzymes Low Platelets (HELLP) syndrome, a complication of preeclampsia/eclampsia, is associated with severe maternal morbidity and mortality. In resource-limited settings, such as Uganda, gaps in routine laboratory assessments may lead to underdetection of HELLP syndrome. This study determined the prevalence and factors associated with HELLP syndrome among pregnant women with preeclampsia/eclampsia at Mbarara Regional Referral Hospital (MRRH), southwestern Uganda.MethodsA cross-sectional study was conducted at the high-risk ward of the MRRH from December 2022 to June 2023. Pregnant women diagnosed with preeclampsia or eclampsia were enrolled consecutively. Participants’ sociodemographic and clinical data were collected using an interviewer-administered questionnaire. The diagnosis of complete HELLP syndrome was made based on the Tennessee classification: aspartate aminotransferase enzyme ≥ 70 IU/L, platelet counts < 100,000 cells/µL, and serum lactate dehydrogenase enzyme ≥ 600 IU/L. We used multivariable modified Poisson regression analysis to determine factors associated with HELLP syndrome.ResultsA total of 129 participants with a mean age of 28 ± 6.6 years were enrolled in the study. The prevalence of HELLP syndrome was 18.6% (n = 24; 95% CI: 12.7–26.3%). Independent factors associated with HELLP syndrome were maternal age (adjusted prevalence ratio [aPR]: 4.96; 95% CI: 1.57–15.65; for mothers aged < 20 years compared to those aged 20–34 years), the presence of epigastric pain (aPR: 5.89; 95% CI: 1.41–14.63), and referral from other health facilities (aPR: 3.14; 95% CI: 1.27–7.72).ConclusionApproximately 2 of the 10 women who presented with preeclampsia or eclampsia had HELLP syndrome. It is more common among teenage mothers, those with a history of epigastric pain and those referred from lower health facilities. Incorporating routine laboratory testing for HELLP syndrome in the diagnostic protocol for preeclampsia or eclampsia, especially among adolescent mothers, those experiencing epigastric pain, and those referred from lower health facilities, could enhance timely detection and management of mothers with preeclampsia whose pregnancies are complicated by HELLP syndrome.

Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.

Representing severe morbidity and mortality globally, respiratory infections associated with chronic respiratory diseases, including complicated pneumonia, asthma, interstitial lung disease, and chronic obstructive pulmonary disease, are a major public health concern. Lung health and the prevention of pulmonary disease rely on the mechanisms of airway surface fluid secretion, mucociliary clearance, and adequate immune response to eradicate inhaled pathogens and particulate matter from the environment. The antimicrobial proteins and peptides contribute to maintaining an antimicrobial milieu in human lungs to eliminate pathogens and prevent them from causing pulmonary diseases. The predominant antimicrobial molecules of the lung environment include human α- and β-defensins and cathelicidins, among numerous other host defense molecules with antimicrobial and antibiofilm activity such as PLUNC (palate, lung, and nasal epithelium clone) family proteins, elafin, collectins, lactoferrin, lysozymes, mucins, secretory leukocyte proteinase inhibitor, surfactant proteins SP-A and SP-D, and RNases. It has been demonstrated that changes in antimicrobial molecule expression levels are associated with regulating inflammation, potentiating exacerbations, pathological changes, and modifications in chronic lung disease severity. Antimicrobial molecules also display roles in both anticancer and tumorigenic effects. Lung antimicrobial proteins and peptides are promising alternative therapeutics for treating and preventing multidrug-resistant bacterial infections and anticancer therapies.

Strengthening cancer care through the inclusion of audiological services

Aim Commonly used cancer treatments that treat the priority cancers are ototoxic. Ototoxicity can add to the already severe morbidity experienced by cancer survivors. It affects the quality of life and consequently has dire psycho-socio-emotional, cognitive, occupational, and scholastic effects. This article aims to highlight that the inclusion of audiological services, such as ototoxicity monitoring and management, can strengthen cancer care by reducing the morbidity and effects of ototoxicity. It explores the current practices of ototoxicity monitoring and management for cancer patients in South Africa and offers practical and innovative evidence-based solutions on how the practice can be improved. The paper also discusses how the National Care Strategic Framework (NCSF) (2017-2022) can be expanded to support the inclusion of audiological services by including ototoxicity monitoring and management in cancer care. Methods A review of literature was conducted utilising a narrative approach to explore audiological service provision for cancer care in South Africa. Peer-reviewed publications and clinical guidelines related to audiological and/or vestibular ototoxicity caused by cancer treatments were reviewed. Findings Despite the inroads that have been made in South Africa, resource and logistical limitations hinder the effectiveness of ototoxicity monitoring and management programmes. In addition, a lack of awareness of the ototoxic effects of some cancer treatments by oncology nurses, as well as ambiguity regarding the roles and responsibilities of the multidisciplinary cancer team in terms of ototoxicity monitoring, management, and patient counselling, further exacerbate the problem. Conclusions The effectiveness of ototoxicity monitoring and management could be enhanced by having a national and standardised protocol and programme incorporating tele-audiology and task-shifting. In addition, collaborative work among the cancer multidisciplinary team will foster holistic practice and integration of audiological services. Future versions of the NCSF should encompass considerations to reduce the associated burdens of cancer treatment, and audiological services, through ototoxicity monitoring, and ought to be included when providing cancer care to patients being treated with ototoxic agents.