bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of an Estimate-of-Risk Model in Critically Ill Obstetric Patients in Brazil
Authors: Silva Flávio X. , Parpinelli Mary A. , Oliveira-Neto Antonio F. , do Valle Carolina Ribeiro , Souza Renato T. , Costa Maria L. , Correia Mario D. T. , Katz Leila , Payne Beth , Ryan Helen , von Dadelszen Peter , Cecatti José G.
Published: December 2021

OBJECTIVE:

To externally validate the CIPHER (Collaborative Integrated Pregnancy High-Dependency Estimate of Risk) prognostic model for pregnant and postpartum women admitted to the intensive care unit.

METHODS:

A retrospective and a prospective validation study were conducted at two reference centers in Brazil. A composite outcome was defined as maternal death or need for prolonged organ support (more than 7 days) or acute lifesaving intervention. To evaluate the performance of the CIPHER model, a receiver operating characteristic curve was used and score calibration was assessed by the Hosmer-Lemeshow test. We conducted a descriptive analysis comparing the results of the current study with the results of the model development study.

RESULTS:

A total of 590 women were included. The composite outcome was observed in 90 (15.2%) women. Of these, 13 (2.2%) were maternal deaths and 77 (13%) required one or more component of organ support or lifesaving intervention. The CIPHER model's area under the curve (AOC) did not show significant predictive ability (AOC 0.53, 95% CI 0.46–0.60), and consequently its calibration was poor (Hosmer-Lemeshow test P<.05).

CONCLUSION:

The CIPHER model for prediction of mortality and need for interventions in critically ill obstetric patients did not perform well in our Brazilian population. Different predictors of morbidity and mortality may need to be used for patients receiving care in public hospitals in low- and middle-income countries.
Management of Placental Transfusion to Neonates After Delivery
Authors: McAdams Ryan M. , Lakshminrusimha Satyan
Published: December 2021

This review summarizes high-quality evidence supporting delayed umbilical cord clamping to promote placental transfusion to preterm and term neonates. In preterm neonates, delayed cord clamping may decrease mortality and the need for blood transfusions. Although robust data are lacking to guide cord management strategies in many clinical scenarios, emerging literature is reviewed on numerous topics including delivery mode, twin gestations, maternal comorbidities (eg, gestational diabetes, red blood cell alloimmunization, human immunodeficiency virus [HIV] infection, and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and neonatal complications (eg, fetal growth restriction, congenital heart disease, and the depressed neonate). Umbilical cord milking is an alternate method of rapid placental transfusion, but has been associated with severe intraventricular hemorrhage in extremely preterm neonates. Data on long-term outcomes are discussed, as well as potential contraindications to delayed cord clamping. Overall, delayed cord clamping offers potential benefits to the estimated 140 million neonates born globally every year, emphasizing the importance of this simple and no-cost strategy.
Risk of Recurrent Stillbirth in Subsequent Pregnancies
Authors: Lamont Kathleen , Scott Neil W. , Gissler Mika , Gatt Miriam , Bhattacharya Sohinee
Published: December 2021

OBJECTIVE:

To compare the prospective risk of stillbirth between women with and without a stillbirth in their first pregnancy.

METHODS:

We conducted a cohort study using perinatal data from Finland, Malta, and Scotland. Women who had at least two singleton deliveries were included. The exposed and unexposed cohorts comprised women with a stillbirth and live birth in their first pregnancy, respectively. The risk of stillbirth in any subsequent pregnancy was assessed using a Cox proportional hazards model. Time-to-event analyses were conducted to investigate whether first pregnancy outcome had an effect on time to or the number of pregnancies preceding subsequent stillbirth.

RESULTS:

The pooled data set included 1,064,564 women, 6,288 (0.59%) with a stillbirth and 1,058,276 with a live birth in a first pregnancy. Compared with women with a live birth, women with a stillbirth in the first pregnancy were more likely to have a subsequent stillbirth (adjusted hazard ratio [aHR] 2.25, 95% CI 1.86–2.72). For women with more than two pregnancies, the difference in risk of subsequent stillbirth between the two groups increased with the number of subsequent pregnancies. Maternal age younger than 25 years or 40 years and older, smoking, low socioeconomic status, not having a partner, pre-existing diabetes, preeclampsia, placental abruption, or delivery of a growth-restricted neonate in a first pregnancy were independently associated with subsequent stillbirth. Compared with women with a live birth in the first pregnancy, women with a stillbirth were more likely to have another pregnancy within 1 year. The absolute risk of stillbirth in a subsequent pregnancy for women with stillbirth and live birth in a first pregnancy were 2.5% and 0.5%, respectively.

CONCLUSION:

Compared with women with a live birth in a first pregnancy, women with a stillbirth have a higher risk of subsequent stillbirth irrespective of the number and sequence of the pregnancies. Despite high relative risk, the absolute risk of recurrence was low.
Association of Skin Incision Type With Postoperative Cesarean Delivery Complications in Morbidly Obese Patients
Authors: Martin Jane , Gastanaduy Mariella , Nakahara Angela , Peterson Sydney , Chai Melinda , Mussarat Naiha , Biggio Joseph
Published: December 2021

OBJECTIVE:

To assess whether Pfannenstiel skin incision compared with vertical skin incision was associated with postcesarean delivery wound complications in morbidly obese women.

METHODS:

We assembled a retrospective cohort of patients with body mass index (BMI) of 40 or higher who delivered by cesarean between July 2012 and May 2019. The primary outcome was a composite wound morbidity (until 42 days postpartum) including wound separation, infection, and dehiscence. Secondary outcomes included individual composite components plus select maternal and neonatal outcomes. Comparisons of demographics and outcomes were made by χ2 and t test. Logistic regression was performed. Subgroup analysis was performed according to location of vertical skin incision in relation to the umbilicus.

RESULTS:

A total of 3,901 patients were included. To account for imbalances in demographics between exposure groups, vertical and Pfannenstiel skin incision patients were matched in a 1:4 fashion for age, BMI, smoking status, and diabetes. The frequency of wound morbidity was 13.2% overall. There was no difference in the primary outcome when comparing Pfannenstiel with vertical skin incision (adjusted odds ratio [aOR] 1.5, 95% CI 0.8–2.8). Patients with a vertical skin incision were more likely to undergo vertical hysterotomy (aOR 138.7, 95% CI 46.9–410) and transfusion (aOR 5.4, 95% CI 1.8–16.5). When vertical skin incision was classified into supraumbilical and infraumbilical, and compared with Pfannenstiel skin incision, infraumbilical vertical skin incision was associated with increased wound morbidity (odds ratio [OR] 2.46, 95% CI 1.4–4.5) and wound infection (OR 2.5, 95% CI 1.4–4.6) compared with Pfannenstiel. Both types of vertical skin incision were associated with increased odds of vertical hysterotomy and transfusion when compared with Pfannenstiel.

CONCLUSION:

In morbidly obese women who underwent cesarean delivery, the frequency of postoperative wound morbidity was similar after Pfannenstiel and vertical skin incisions.
Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes
Authors: Smid Marcela C. , Metz Torri D. , McMillin Gwen A. , Mele Lisa , Casey Brian M. , Reddy Uma M. , Wapner Ronald J. , Thorp John M. , Saade George R. , Tita Alan T. N. , Miller Emily S. , Rouse Dwight J. , Sibai Baha , Costantine Maged M. , Mercer Brian M. , Caritis Steve N. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*
Published: December 2021

OBJECTIVE:

To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes.

METHODS:

We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8–20 weeks of gestation. All maternal–child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment.

RESULTS:

Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians −2.47, 95% CI −6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians −1.35, 95% CI −7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11–10.89).

CONCLUSIONS:

Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00388297.
The Motherhood Penalty in Obstetrics and Gynecology Training
Authors: Polan Rosa M. , Mattei Larissa H. , Barber Emma L.
Published: December 2021

Since 2017, the number of women enrolled in medical schools in the United States has increased steadily. For the average female graduate, residency training will coincide with peak childbearing years. Despite increasingly well-defined parental leave policies in other industries, there is no standardized approach across graduate medical education programs. Physician mothers, particularly those in surgical specialties, have also been shown to be at increased risk for major pregnancy complications and postpartum depression. In addition, despite excellent initiation rates, the majority of breastfeeding trainees struggle with low milk supply, and as few as 7% of physician mothers continue to breastfeed for 1 year. Although the medical field routinely advocates for the benefits of parental leave and breastfeeding for our patients, significant and comprehensive change is needed to ensure that graduate medical education trainees can follow physician-recommended postpartum guidelines without meaningful implications for their careers. In February 2020, the American Board of Obstetrics and Gynecology changed its leave policy, allowing residents to take up to 12 weeks of paid or unpaid leave in a single year for vacation, parenting, or medical issues without extending their training. This change represents an important first step, and, as comprehensive women's health care professionals, our specialty should be leaders in normalizing family building for physicians-in-training. A culture change toward an environment of support for pregnant and parenting trainees and access to affordable, extended-hour childcare are also critical to enabling physicians at all levels to be successful in their careers.
Pessary Plus Progesterone to Prevent Preterm Birth in Women With Short Cervixes
Authors: Pacagnella Rodolfo C. , Silva Thaís V. , Cecatti José G. , Passini Renato , Fanton Tatiana F. , Borovac-Pinheiro Anderson , Pereira Cynara M. , Fernandes Karayna G. , França Marcelo S. , Li Wentao , Mol Ben W. ,   for The P5 Working Group
Published: December 2021

OBJECTIVE:

To test the effectiveness of cervical pessary in addition to vaginal progesterone for the prevention of preterm birth in women with midpregnancy short cervixes.

METHODS:

We performed a multicenter, open-label, randomized controlled trial in 17 perinatal centers. Asymptomatic women with singleton or twin pregnancies and cervical lengths of 30 mm or less, measured at 18 0/7–22 6/7 weeks of gestation, were randomized to cervical pessary plus vaginal progesterone (pessary plus progesterone group) or vaginal progesterone only (progesterone-only group) (200 mg/day). Treatments were used from randomization to 36 weeks of gestation or delivery. The primary outcome was a composite of neonatal mortality and morbidity. Secondary outcomes were delivery before 37 weeks and before 34 weeks of gestation. Analysis was performed according to intention to treat.

RESULTS:

Between July 9, 2015, and March 29, 2019, 8,168 women were screened, of whom 475 were randomized to pessary and 461 to progesterone only. The composite perinatal outcome occurred in 19.2% (89/463) of the women in the pessary group compared with 20.9% (91/436) of the women in the progesterone-only group (adjusted risk ratio [aRR] 0.88, 95% CI 0.69–1.12). Delivery rates before 37 weeks of gestation were 29.1% compared with 31.4% (aRR 0.86, 95% CI 0.72–1.04); delivery rates before 34 weeks were 9.9% compared with 13.9% (aRR 0.66, 95% CI 0.47–0.93). Women in the pessary group had more vaginal discharge (51.6% [245/476] vs 25.4% [117/479] [P<.001]), pain (33.1% [157/476] vs 24.1% [111/479] [P=.002]), and vaginal bleeding (9.7% [46/476] vs 4.8% [22/479] [P=.004]).

CONCLUSION:

In asymptomatic women with short cervixes, the combination of pessary and progesterone did not decrease rates of neonatal morbidity or mortality when compared with progesterone only.

CLINICAL TRIAL REGISTRATION:

Brazilian Clinical Trial Registry (ReBec), UTN:U1111-1164-2636.
Caring for Unvaccinated Patients in the ICU: Beyond Frustration, Toward Beneficial Relationships
Authors: Bibler Trevor M. , Nelson Ryan H. , Schuman Olivia , Miller Susan M.
Published: December 2021

Critical care professionals in the United States are experiencing distress and frustration during the recent delta-wave of the coronavirus disease 2019 pandemic. This wave feels different because most, although not all, patients suffering with the sequelae from coronavirus disease 2019 who enter ICUs are unvaccinated. Since vaccines in the United States are safe, effective, and widely available for people 12 and older, severe cases of coronavirus disease 2019 are now considered preventable. However, even when a disease is preventable, critical care professionals still have remaining role-based, ethical obligations to their patients. Developing additional mechanisms for reflection and resilience, in spite of accumulated frustrations from otherwise preventable mortality, may help the professional and those they care for. In this essay, we propose a number of questions that recognize the existential frustrations critical care professionals experience, while also uncovering the ethical obligations that remain. Rather than becoming comfortable with silence or frustration, these reflections intend to bridge the gap between feeling frustrated and building relationships that benefit both the patient and the critical care professional during this pandemic.
Microbe-based management for colorectal cancer
Authors: Gao Zi-Yun , Cui Zhe , Yan Yu-Qing , Ning Li-Jun , Wang Zhen-Hua , Hong Jie
Published: December 2021

Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such asenterotoxigenic Bacteroides fragilis(ETBF) andStreptococcus gallolyticus(S. gallolyticus), as well as protective bacterial such asAkkermansia muciniphila(A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.
Psychotropic Medication Use by Children with Autism Served in Publicly Funded Mental Health Settings
Authors: Caplan Barbara , Chlebowski Colby , May Gina , Baker-Ericzén Mary J. , Connor Willard , Brookman-Frazee Lauren
Published: December 2021

Objective:

The aim of this study was to characterize patterns of and factors associated with psychotropic medication use in children with autism spectrum disorder (ASD) receiving publicly funded mental health services.

Method:

Data were extracted from 202 children with ASD participating in a cluster randomized trial of An Individualized Mental Health Intervention for ASD conducted in 29 publicly funded mental health programs. Children with ASD were aged 5 to 13 years (M = 9.1 years, SD = 2.4), and were 84.2% male and 59.9% Latinx. Child ASD and cognitive functioning were determined by standardized assessment. Caregivers reported child psychotropic medication use, behavior problems, ASD symptom severity, mental health symptoms, family demographics, and caregiver strain at the baseline.

Results:

Nearly half (49.5%) of participants used psychotropic medication(s) within the past 6 months, with stimulants being most commonly reported. Child co-occurring attention-deficit/hyperactivity disorder (ADHD) (B = 1.55, p < 0.01; 95% confidence interval [CI]: 0.53–2.57), lower cognitive functioning (B = −0.03, p = 0.02; 95% CI: −0.05 to <0.00), and non-Hispanic White ethnicity (vs Hispanic/Latinx; B = 1.02, p = 02; 95% CI: −1.89 to −0.14) were associated with a greater likelihood of using any type of medication. Factors associated with medication use varied by class: stimulants—ADHD, lower ASD symptom severity, and more intensive behavior problems; SSRIs—higher ASD symptom severity; alpha-2 agonists—ADHD, higher ASD symptom severity, lower cognitive functioning, and higher caregiver strain; and antipsychotics—none.

Conclusion:

The findings highlight factors associated with psychotropic medication use for a clinically complex population, which may inform community care improvement efforts.
Patterns and Correlates of Changes in Emotional and Behavioral Problems Among Children with Congenital Heart Disease
Authors: Hsiao Lu-Chi , Chiu Shuenn-Nan , Chang Ling-Yin , Wang Chia-Ching , Weng Wen-Chin , Chang Hsing-Yi
Published: December 2021

Objective:

The objective of this study was to examine patterns of changes in emotional and behavioral problems among children with congenital heart disease (CHD) and investigate associated factors in different domains.

Method:

The study sample comprised 327 pairs of children with CHD (aged 1.5–12 yrs) and their parents who participated in 2 waves of a survey in Taiwan from 2017 to 2019. The Child Behavior Checklist was used to evaluate the children's emotional and behavioral problems during both waves. The scores were later used to determine the patterns of changes in emotional and behavioral problems. Multinomial logistic regression was then applied to examine factors associated with varied patterns of changes in emotional and behavioral problems.

Results:

Five patterns of changes in emotional and behavioral problems were identified: “persistent normal,” “initial problematic,” “worsening,” “persistent problematic,” and “subclinical.” Among the factors examined, parenting stress was consistently associated with different patterns of change in emotional and behavioral problems. Specifically, children with parents who had higher levels of parenting stress were more likely to belong to the “initial problematic,” “persistent problematic,” or “subclinical” groups than to the “persistent normal” group. Other significant factors included sex, number of surgeries, and perceived health of parents.

Conclusion:

This study highlights the potential role of parenting stress in changes in emotional and behavioral problems. Accordingly, intervention programs aimed at relieving parenting stress may help reduce the development and worsening of emotional and behavioral problems among children with CHD.
Perceptions of obesity pharmacotherapy by nurse practitioners
Authors: Bottcher Katelyn , Chao Ariana M.
Published: December 2021

Five medications are approved by the US Food and Drug Administration for chronic weight management, yet less than 2% of adults with obesity use these medications. The purpose of this study was to identify reasons nurse practitioners are reluctant to prescribe obesity pharmacotherapy. This was a cross-sectional study of a US sample of nurse practitioners. Questionnaires were administered online that evaluated practice patterns and attitudes concerning obesity pharmacotherapy. The survey was completed by 74 nurse practitioners, and of those, 17.6% prescribed obesity pharmacotherapy and 82.4% did not. Nurse practitioners who did and did not prescribe obesity pharmacotherapy had similar scores on weight bias. Nurse practitioners who did not prescribe obesity pharmacotherapy, compared with those who did, more often reported that patients do not ask for obesity pharmacotherapy (p = .01), patients did not want to use pharmacotherapy (p = .02), and that they were not familiar with obesity medications (p = .02). Although this survey was limited by a low response, we found many beliefs, opinions, and attitudes toward adults with obesity did not differ between the groups. However, nurse practitioners who did not prescribe obesity pharmacotherapy, compared with those who did, identified more barriers related to the lack of obesity pharmacotherapy awareness and education.
Relationship between noninvasive central blood pressure and brain natriuretic peptide levels in patients with hypertensive pulmonary edema
Authors: Algowhary Magdy Ibrahim Aldesowky Mohammed , Razik Nady A. , Youssef Amr Ahmed Aly , Fouad Lateef Gerges Lateef , Hassan Ayman Khairy M.
Published: December 2021

Objective

Hypertensive pulmonary edema is a fatal condition unless early and properly diagnosed and managed. Central blood pressure (cBP) has been proven to be more associated with adverse cardiovascular events. We aimed to study the correlation between cBP and heart damage in patients with Hypertensive pulmonary edema.

Methods

We included 50 patients admitted to the emergency department in a university hospital for hypertensive pulmonary edema, 27 women and 23 men aged 50 to 70 years. We excluded patients with suspected acute coronary syndrome, significant valvular heart disease, and pericardial diseases. We measured cBP non-invasively from pulse wave analysis of the brachial artery. Brain natriuretic peptide (BNP) and cBP were repeatedly measured for every patient.

Results

The median BNP levels of patients significantly decreased from 284 pg/ml (232–352.5) to 31.5 pg/ml (24–54) on discharge, P < 0.001. We found a significant correlation between admission BNP and central SBP (cSBP), urea, creatinine, arterial blood gases parameters, and left ventricular end-diastolic diameter (LVEDD). Concurrently, BNP at discharge was correlated with age, central DBP (cDBP), urea, creatinine, LVEDD, partial oxygen pressure (pO2), and oxygen saturation (SO2). Delta BNP was correlated with cSBP, peripheral SBP, urea, creatinine, pO2, and SO2. Linear regression analysis revealed that creatinine, and cSBP, were independent predictors of admission BNP, while urea and cDBP were the independent predictors of discharge BNP.

Conclusion

This simple, noninvasive method of cBP measurement was significantly associated with the extent of myocardial damage in patients presenting with hypertensive pulmonary edema.
Blood pressure altering method affects correlation with pulse arrival time
Authors: Heimark Sondre , Rindal Ole Marius H. , Seeberg Trine M. , Stepanov Alexey , Boysen Elin S. , Bøtker-Rasmussen Kasper G. , Mobæk Nina K. , Søraas Camilla L. , Stenehjem Aud E. , Fadl Elmula Fadl Elmula M. , Waldum-Grevbo Bård
Published: December 2021

Objective

Pulse arrival time (PAT) is a potential main feature in cuff-less blood pressure (BP) monitoring. However, the precise relationship between BP parameters and PAT under varying conditions lacks a complete understanding. We hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and both SBP and DBP. Therefore, this study aimed to investigate the correlation between PAT and BP during two exercise modalities with differing BP responses using an unobtrusive wearable device.

Methods

Seventy-five subjects, of which 43.7% had a prior diagnosis of hypertension, participated in an isometric and dynamic exercise test also including seated periods of rest prior to, in between and after. PAT was measured using a prototype wearable chest belt with a one-channel electrocardiogram and a photo-plethysmography sensor. Reference BP was measured auscultatory.

Results

Mean individual correlation between PAT and SBP was −0.82 ± 0.14 in the full protocol, −0.79 ± 0.27 during isometric exercise and −0.77 ± 0.19 during dynamic exercise. Corresponding correlation between PAT and DBP was 0.25 ± 0.35, −0.74 ± 0.23 and 0.39 ± 0.41.

Conclusion

The results confirm PAT as a potential main feature to track changes in SBP. The relationship between DBP and PAT varied between exercise modalities, with the sign of the correlation changing from negative to positive between type of exercise modality. Thus, we hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and BP with emphasis on DBP.
Cause-Specific Mortality as a Sequalae of Perioperative Stroke Following Cardiac and Vascular Surgery
Authors: Reinert Nathan J. , Patel Bansri M. , AlShaer Qasem N. , Wu Liwen , Wisniewski Stephen , Hager Eric S. , Dyer Mitchell R. , Thirumala Parthasarathy D.
Published: December 2021

Background:

There is a paucity of data regarding cause-specific mortality following a perioperative stroke. In this study, we aim to establish the risk of cause-specific mortality associated with perioperative stroke following cardiac and vascular procedures at 30 days, 90 days, and 1-year postoperative. It is hoped that this fund of knowledge will enhance perioperative risk stratification and medical management for patients who have suffered a perioperative stroke.

Methods:

This is a retrospective cohort study evaluating 277,654 cardiac and vascular surgical patients dually documented within the Inpatient Discharge Claims Database and the Pennsylvania Department of Health Death Statistics database. A univariate assessment followed by a multivariate logistic regression analysis was used to determine the odds of cerebrovascular, cardiovascular, pulmonary, malignancy, infectious, and dementia causes of mortality following perioperative stroke.

Results:

Perioperative stroke significantly increased the odds of overall mortality (P<0.0001) as well as cause-specific mortality in all categories (P<0.05) except dementia (P=0.8907) at all-time endpoints. Cerebrovascular-related mortality was most impacted by perioperative stroke [adjusted odds ratio: 34.5 (29.1, 40.9), P<0.0001 at 30 d].

Conclusions:

Perioperative stroke in the cardiac and vascular surgical population is associated with increased odds of overall, cerebrovascular, cardiovascular, pulmonary, malignancy, and infectious causes of mortality at 30 days, 90 days, and 1-year postoperatively when compared with patients who did not experience a perioperative stroke.
Cerebral Venous Sinus Thrombosis Associated With Coronavirus Disease 2019
Authors: Panichpisal Kessarin , Ruff Ilana , Singh Maharaj , Hamidi Massihullah , Salinas Pedro D. , Swanson Kyle , Medlin Stephen , Dandapat Sudeepta , Tepp Payton , Kuchinsky Genevieve , Pesch Amy , Wolfe Thomas
Published: December 2021

Introduction:

Coronavirus disease 2019 (COVID-19) is associated with significant risk of acute thrombosis. We present a case report of a patient with cerebral venous sinus thrombosis (CVST) associated with COVID-19 and performed a literature review of CVST associated with COVID-19 cases.

Case Report:

A 38-year-old woman was admitted with severe headache and acute altered mental status a week after confirmed diagnosis of COVID-19. Magnetic resonance imaging brain showed diffuse venous sinus thrombosis involving the superficial and deep veins, and diffuse edema of bilateral thalami, basal ganglia and hippocampi because of venous infarction. Her neurological exam improved with anticoagulation (AC) and was subsequently discharged home. We identified 43 patients presenting with CVST associated with COVID-19 infection. 56% were male with mean age of 51.8±18.2 years old. The mean time of CVST diagnosis was 15.6±23.7 days after onset of COVID-19 symptoms. Most patients (87%) had thrombosis of multiple dural sinuses and parenchymal changes (79%). Almost 40% had deep cerebral venous system thrombosis. Laboratory findings revealed elevated mean D-dimer level (7.14/mL±12.23 mg/L) and mean fibrinogen level (4.71±1.93 g/L). Less than half of patients had prior thrombotic risk factors. Seventeen patients (52%) had good outcomes (mRS <=2). The mortality rate was 39% (13 patients).

Conclusion:

CVST should be in the differential diagnosis when patients present with acute neurological symptoms in this COVID pandemic. The mortality rate of CVST associated with COVID-19 can be very high, therefore, early diagnosis and prompt treatment are crucial to the outcomes of these patients.
Acute Lymphoblastic Leukemia Masquerading as Guillain-Barré Syndrome
Authors: Al-Chalabi Mustafa , Ali Nasar , Lim Taehong , Khalid Fatima , Mccracken Matthew , Alam Abdullah , Meisler Adam , Pirzada Noor
Published: December 2021

Introduction:

Neurological manifestations of acute lymphoblastic leukemia (ALL) have been reported as cranial neuropathies or meningeal symptoms most common in children. However, ALL can rarely involve the nerve roots causing symmetrical polyradiculopathy which can present with rapid onset paralysis, mimicking Guillain-Barré Syndrome (GBS). The symmetrical polyradiculopathy can be the earliest manifestation of ALL occurring even before the hematological and systemic manifestations.

Case Report:

We report a case of a healthy 29-year-old man who presented with subacute bilateral lower extremity weakness and numbness preceded by a respiratory infection. He was initially treated as a suspected (GBS) but cerebrospinal fluid (CSF) findings suggested an alternative diagnosis. His prior TB exposure created a diagnostic confusion. Lumbar spine magnetic resonance imaging revealed nerve root enhancements at L4-L5 and L5-S1 that are seen in GBS and TB arachnoidids. Brain magnetic resonance imaging demonstrated bilateral distention of the optic nerve sheath complexes with CSF suggestive of intracranial hypertension. CSF revealed elevated protein, nucleated cells 2145 leukocytes/mm3, numerous atypical lymphoid cells. He was later diagnosed with ALL associated symmetrical polyradiculopathy presenting with GBS-like symptoms.

Conclusion:

Symmetrical polyradiculopathy is a rare complication of ALL and can be confused with acute inflammatory demyelinating polyneuropathy. ALL associated polyradiculopathy in young individuals can be clinically indistinguishable from GBS. Our case highlights that when CSF findings are atypical for GBS, ALL should be considered on the differential diagnosis in patients presenting with GBS like symptoms.
Postchemotherapy Endometrioid to Gastrointestinal Histotype Shift in Recurrent Endometrial Carcinoma
Authors: Arciuolo Damiano , Travaglino Antonio , Santoro Angela , Pedone Anchora Luigi , Inzani Frediano , Angelico Giuseppe , D’Alessandris Nicoletta , Scaglione Giulia , Valente Michele , Raffone Antonio , Fanfani Francesco , Zannoni Gian F.
Published: December 2021

Herein, we report a case of low-grade endometrial endometrioid carcinoma recurred on the vaginal stump, which showed a complete histotype shift toward a gastrointestinal-type carcinoma after chemotherapy. The recurrent tumor increased in volume during chemotherapy. Postchemotherapy histologic examination showed a pure mucinous signet-ring cell pattern with positivity for cytokeratin 20 and CDX2, focal SATB2 expression and negativity for cytokeratin 7 and estrogen and progesterone receptors. Such features led to consider a diagnosis of metastasis from a primary carcinoma of the gastrointestinal tract. The accurate exclusion of any primary lesions of gastrointestinal and of other sites allowed identifying the tumor as the recurrent endometrial carcinoma. Our case highlights that chemotherapy may induce a histotype shift from endometrioid carcinoma to gastrointestinal-type carcinoma; such occurrence might be a mechanism of resistance and might provide new insights on the sensitiveness of different histotypes to systemic therapies. Considering the possibility of a shift from endometrioid to gastrointestinal-type carcinoma may be useful for a correct diagnosis and an appropriate patient management.
Adult Granulosa Cell Tumor With Sarcomatous Transformation: A Case Study With Emphasis on Molecular Alterations
Authors: Dahoud Wissam , Handler Jesse , Parimi Vamsi , Meyer Christian F. , Wethington Stephanie L. , Eshleman James R. , Vang Russell , Ronnett Brigitte M. , Xing Deyin
Published: December 2021

Adult granulosa cells tumors (AGCTs) are typically low-grade indolent tumors. On rare occasions, they undergo high-grade/sarcomatous transformation and behave aggressively. This transformation is postulated to occur as the result of acquired genetic alterations, some of which may be eligible for targeted therapy. Here we report a rare case of AGCT with sarcomatous transformation that harbored distinct molecular alterations from those typically seen with AGCTs supporting a molecularly driven approach to these malignancies. The patient is a 56-yr-old G3P3 woman with a history of multiple recurrences of ovarian AGCT for which the first diagnosis was made at the age of 25 when she was evaluated for infertility. The ovarian tumor displayed typical features of AGCT with low-grade, bland morphology. The first extraovarian spread of tumor involving the cul-de-sac was reported at the age of 39. After that, recurrences occurred every 2 to 3 yr with involvement of multiple anatomic sites and repeated surgical resections. At the age of 55 she developed a symptomatic recurrence in the pelvis and underwent resection of an isolated lesion (specimen 1) to no gross residual disease. Within 4 wk of resection she developed significant pelvic pain and imaging showed recurrence of the mass. Therefore, in 5 mo after the initial resection she underwent repeat excision of the lesion (specimen 2) and associated bowel. The sections from specimen 1 showed a biphasic morphology: a low-grade component with morphology and immunophenotype consistent with a typical AGCT and a high-grade spindle cell component with features consistent with a high-grade sarcoma. Specimen 2 featured a pure high-grade sarcoma characterized by coagulative tumor cell necrosis, readily recognizable mitoses, highly atypical cells with vesicular nuclei and prominent nucleoli. SF-1 positivity and the presence of FOXL2 C134W mutation in the sarcomatous component support the notion of transformation of typical AGCT. While detected TERT promoter C228T mutation may play a role in this process, we further identified genetic alterations affecting PI3K/AKT/mTOR pathway, including mutations in PIK3CA, PIK3R1, AKT1, and NF2, which may also contribute to tumor progression/transformation. These findings provide rationale for molecular/pathway-based targeted therapy for patients with advanced AGCT.
Adenovirus Infection and Transplantation
Authors: Al-Heeti Omar M. , Cathro Helen P. , Ison Michael G.
Published: December 2021

Adenoviruses result in a wide array of clinical presentations, including primarily respiratory, gastrointestinal, genitourinary, or systemic infections. Although adenovirus causes mild disease limited to a single organ system in immunocompetent individuals, severe and life-threatening infections do rarely occur. Disseminated disease and severe localized disease resulting in significant morbidity and mortality have been well described in the immunocompromised populations. Although asymptomatic viremia, respiratory tract, and gastrointestinal infections are the most common disease in most transplant patients, renal transplant patients more commonly experience urinary tract infections, including hemorrhagic cystitis or nephritis. Diagnosis requires astute clinical awareness of the patient’s clinical presentation that would be compatible with adenovirus combined with cultures, molecular testing, polymerase chain reaction, and tissue sampling. There is no Food and Drug Administration–approved treatment for adenovirus; however, several studies have evaluated therapeutic options including cidofovir, brincidofovir, and immunotherapy. This article will summarize our current understanding of adenovirus in the transplant population.
Convalescent plasma for outpatients with early COVID-19
Authors: Millat-Martinez Pere , Gharbharan Arvind , Alemany Andrea , Rokx Casper , Geurtsvankessel Corine , Papageourgiou Grigorios , van Geloven Nan , Jordans Carlijn , Groeneveld Geert , Swaneveld Francis , van der Schoot Ellen , Corbacho-Monné Marc , Ouchi Dan , Ferreira Francini Piccolo , Malchair Pierre , Videla Sebastian , García Vanesa García , Ruiz-Comellas Anna , Ramírez-Morros Anna , Codina Joana Rodríguez , Simon Rosa Amado , Grifols Joan-Ramon , Blanco Julian , Blanco Ignacio , Ara Jordi , Bassat Quique , Clotet Bonaventura , Baro Bàrbara , Troxel Andrea , Zwaginga Jaap Jan , Mitjà Oriol , Rijnders Bart ,   for the ConV-ert,   CoV-Early and COMPILEhome study groups
Published: December 2021

Background

Convalescent plasma (CP) for hospitalized patients with COVID-19 has not demonstrated clear benefits. However, data on outpatients with early symptoms are scarce. We aimed to assess whether treatment with CP administered during the first 7 days of symptoms reduced the disease progression or risk of hospitalization of outpatients.

Methods

Two double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of their predefined sample size had been recruited. A Bayesian adaptive individual patient data meta-analysis was implemented. Analyses were done with Bayesian proportional odds and logistic models, where odds ratios (OR)<1.0 indicate a favorable outcome for CP. Fourteen study sites across the Netherlands and Catalonia in Spain participated in the trial. The two studies included outpatients aged ≥50 years and diagnosed with COVID-19 and symptomatic for ≤7days. The intervention consisted of one unit (200-300mL) of CP with a predefined minimum level of antibodies. The two primary endpoints were (a) a 5-point disease severity scale (fully recovered by day 7 or not, hospital or ICU admission and death) and (b) a composite of hospitalization or death.

Results

Of 797 patients included, 390 received CP and 392 placebo. At baseline, they had a median age of 58 years, 1 comorbidity, symptoms for 5 days and 93% tested negative for SARS-CoV-2 S-protein IgG antibodies. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The OR of CP for an improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311). The OR for hospitalization or death was 0.919 (CI 0.592-1.416). The effect of CP on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95% CI 0.394-1.085). CP did not decrease the time to full symptom resolution (p=0.62).

Conclusion

Treatment with CP of outpatients in the first 7 days of symptoms did not improve the outcome of COVID-19. The possible beneficial effect in patients with ≤5 days of symptoms requires further study.

Registration

NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov

Funding source

ZONMW, the Netherlands, grant number 10430062010001.

SUPPORT-E, grant number 101015756

YoMeCorono, www.tomecorono.com

The Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A
SARS-COV-2 INFECTION IN PRIMARY CARE: A SINGLE-CENTERED, RETROSPECTIVE, OBSERVATIONAL STUDY
Authors: de Yébenes Pilar Galicia García , Gutiérrez Cuevas Juan José , Chen Chen Fang Fang , Larrégola Laura Santos , Briega Alberto Manzanares , Rufo Manuel Linares
Published: December 2021

Purpose

to describe the clinical characteristics of patients with confirmed SARS-CoV-2 infection in primary care and to analyze the predictive role of different risk factors on prognosis, especially living conditions.

Methods

Retrospective longitudinal observational retrospective study by reviewing medical records from a primary care center since March 1 to April 30, 2020. Case definition of confirmed SARS-CoV-2 infection, sociodemographic data, clinical characteristics, comorbidity and living conditions were collected. The statistical analysis consisted in description of the sample, comparison of prognosis groups and analysis of prognostic factors.

Results

A sample of 70 patients with confirmed SARS-CoV-2 infection was obtained, with comorbidity mainly related to arterial hypertension, overweight/obesity, hypercholesterolemia, diabetes and chronic pulmonary pathology. Pneumonia was present in 66%. Exitus occurred in 14% of the sample. Factors associated with mortality were advanced age (84 vs 55; p<0.0001), arterial hypertension (78% vs 41%; p=0.040), asthma-COPD (56% vs 13%; p=0.008) and atrial fibrillation (56% vs 5%; p=0.001).

Conclusions

The study reflects the clinical practice of a primary care center. This kind of studies are essential to strengthen and reorganize the Health System and to try to anticipate the medium- to long-term consequences of COVID-19 on global health.
A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma
Authors: Pal Sharmistha , Kaplan Jakub P. , Nguyen Huy , Stopka Sylwia A. , Savani Milan R. , Regan Michael S. , Nguyen Quang-De , Jones Kristen L. , Moreau Lisa A. , Peng Jingyu , Dipiazza Marina G. , Perciaccante Andrew J. , Zhu Xiaoting , Hunsel Bradley R. , Liu Kevin X. , Drissi Rachid , Filbin Mariella G. , McBrayer Samuel K. , Agar Nathalie Y.R. , Chowdhury Dipanjan , Haas-Kogan Daphne
Published: December 2021

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pathway for pyrimidine biosynthesis. A clinical stage inhibitor of DHODH (rate limiting enzyme in the de novo pathway) diminishes UMP pools, generates DNA damage, and induces apoptosis through suppression of replication forks--an “on target” effect, as shown by uridine rescue. MALDI mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.
Contrasting adaptation and optimization of stomatal traits across communities at continental-scale
Authors: Liu Congcong , Sack Lawren , Li Ying , He Nianpeng
Published: December 2021

The maximum stomatal conductance (g), a major anatomical constraint on plant productivity, is a function of the stomatal area fraction (f) and stomatal space-use efficiency (e). However,fandghave been considered as equivalents, witherarely considered, and their adaptation to the environment and their regulation of ecosystem productivity are unclear. Here, we analyzed the community-weighted mean, variance, skewness, and kurtosis of stomatal traits from tropical to cold-temperature forests. The variance ofgandfwas higher for arid sites, indicating greater functional niche differentiation, whereas that forewas lower, indicating convergence in efficiency. Besides, when other stomatal trait distributions remained unchanged, increasing kurtosis but decreasing skewness ofgwould improve ecosystem productivity, andfshowed the opposite patterns. These findings highlight how the relative importance and equivalence of inter-related traits can differ at community scale.
Broad neutralization of SARS-CoV-2 variants, including omicron, following breakthrough infection with delta in COVID-19 vaccinated individuals
Authors: Lechmere Thomas , Snell Luke B. , Graham Carl , Seow Jeffrey , Shalim Zayed A. , Charalampous Themoula , Alcolea-Medina Adela , Batra Rahul , Nebbia Gaia , Edgeworth Jonathan D. , Malim Michael H. , Doores Katie J.
Published: December 2021

Numerous studies have shown that a prior SARS-CoV-2 infection can greatly enhance the antibody response to COVID-19 vaccination, with this so called “hybrid immunity” leading to greater neutralization breadth against SARS-CoV-2 variants of concern. However, little is known about how breakthrough infection (BTI) in COVID-19 vaccinated individuals will impact the magnitude and breadth of the neutralizing antibody response. Here, we compared neutralizing antibody responses between unvaccinated and COVID-19 double vaccinated individuals (including both AZD1222 and BNT162b2 vaccinees) who have been infected with the delta (B.1.617.2) variant. Rapid production of Spike-reactive IgG was observed in the vaccinated group providing evidence of effective vaccine priming. Overall, potent cross-neutralizing activity against current SARS-CoV-2 variants of concern was observed in the BTI group compared to the infection group, including neutralization of the omicron (B.1.1.529) variant. This study provides important insights into population immunity where transmission levels remain high and in the context of new or emerging variants of concern.