bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of US Obstetric Anesthesiologists’ Perceived Value of Obstetric Anesthesiology Fellowship
Authors: Thomas C , Neumann KE , Smith C , Dominguez JE , Traynor A , Farber MK , Zakowski M , McCarthy RJ , Peralta FM
Published: August 2024

(Int J Obstet Anesth. 2023;56:103930. doi: 10.1016/j.ijoa.2023.103930|)

In the United States, specialized training in obstetric anesthesiology is linked to better patient outcomes and lower risks during childbirth. A consensus statement from 2015, endorsed by major medical bodies, advocates for concentrating high-risk obstetric services to improve maternal health. The statement suggests specific staffing guidelines for different levels of perinatal centers, emphasizing the need for obstetric anesthesiologists at advanced facilities to handle complex cases and ensure quality care of high-risk patients. Despite efforts to centralize care, many high-risk patients still deliver in community, nonreferral hospitals. Furthermore, there continues to be increased demand for more fellowship-trained obstetric anesthesiologists. This scarcity might stem from various factors, including perceptions about the necessity of specialized training, financial concerns, and insufficient exposure during residency. Detailed information on the career paths of fellowship-trained individuals is limited but could potentially alter perceptions, increase interest in fellowships, and improve recruitment to this subspecialty. This study assesses the perceived benefits of obstetric anesthesiology training on career development, job satisfaction, quality of life, and professional autonomy.
Of Aspirin, Preeclampsia, and Racism
Authors: Sacks DA , Incerpi MH
Published: August 2024

(N Engl J Med. 2024;390(11):968–969. doi: 10.1056/NEJMp2311019)

Being African American/Black was listed as a factor associated with a moderate level of preeclampsia risk in 2018 as outlined by the American College of Obstetricians and Gynecologists (ACOG) committee. This opinion was also re-affirmed in 2023. In 2021 and again in 2022, ACOG cited it as a proxy for the adverse effects of racism on health and mentioned that Black race on its own could be an indication for the need for aspirin. In general, if more than one moderate risk factor was present, a low dose of aspirin could be used to help prevent preeclampsia. This article investigates whether race itself is a risk factor, the potential role of structural racism contributing to preeclampsia, and whether aspirin helps prevent it in this demographic.
Immunosuppressant Medications in Pregnancy
Authors: Saad AF , Pacheco LD , Saade GR
Published: August 2024

(Obstet Gynecol. 2024;143(4):e94–e106. doi: 10.1097/AOG,0000000000005512)

Pregnant patients often take immunosuppressant medications for solid organ transplant rejection prevention or autoimmune disorders. It is important that they adhere to prescribed regimens before and during pregnancy to avoid serious consequences. Close monitoring of organ function, signs of rejection, and immunosuppressant levels are vital. Counseling for reproductive patients should include discussions on how pregnancy may impact their condition, potential fetal effects of medications, and breastfeeding considerations. This review provides detailed guidance on managing common immunosuppressants during pregnancy and lactation, along with antenatal and postpartum care timelines.
RSV Prefusion F Protein-Based Maternal Vaccine—Preterm Birth and Other Outcomes
Authors: Dieussaert I , Kim JH , Luik S , Seidl C , Pu W , Stegmann JU , Swamy GK , Webster P , Dormitzer PR
Published: August 2024

(N Engl J Med. 2024;390(11):1009–1021. doi: 10.1056/NEJMoa2305478)

Maternal immunization could protect infants from respiratory syncytial virus (RSV). GlaxoSmithKline (GSK) developed an RSV subunit vaccine for maternal use called RSVPreF3-Mat. However, during a phase 3 trial (RSV MAT-009) initiated in 2020, an imbalance in preterm births was observed in the vaccine group compared with the placebo group. Consequently, enrollment and vaccination were stopped in February 2022, prompting further investigation. This article presents the primary efficacy and safety findings from the trial, along with exploratory analyses examining the preterm birth safety signal.
Outcomes in Children After Mild Neonatal Hypoxic Ischemic Encephalopathy: A Population-Based Cohort Study
Authors: Törn AE , Hesselman S , Johansen K , Ågren J , Wikström AK , Jonsson M
Published: August 2024

(BJOG. 2023;130(13):1602–1609. doi: 10.1111/1471-0528.17533)

The condition known as neonatal hypoxic ischemic encephalopathy (HIE) occurs when a term or near-term infant suffers asphyxiation during or near birth. The resulting signs and symptoms vary and may be classified as mild, moderate, or severe. Historically, infants diagnosed with mild HIE received alternative, and less intensive care given the understanding that outcomes were less severe compared with infants with the moderate or severe HIE diagnosis. However, recent studies have suggested young children (aged 2 to 5) who were diagnosed with mild HIE as infants are more likely to have a disability when compared with similar aged children without an HIE diagnosis. In addition, when examining mild HIE patients at neonatal discharge, abnormal results were found on amplitude-integrated electroencephalography, brain magnetic resonance imaging, and neurological exam. This population-based cohort study used register-based data to further understand how mild HIE relates to severe neurological outcomes, including death up to 6 years after birth.
High Neuraxial Block in Obstetrics: A 2.5-year Nationwide Surveillance Approach in the Netherlands
Authors: Beenakkers ICM , Schaap TP , van den Bosch OFC
Published: August 2024

(Anesth Analg. 2024. doi: 10.1213/ANE.0000000000006866)

High neuraxial block (HNB) is rare but is the most common serious complication in obstetric anesthesiology. It can occur after the failure of labor epidural anesthesia to convert to cesarean delivery (CD) anesthesia and can lead to respiratory distress and cardiac arrest. The aim of this study was to learn more about the incidence and clinical features of HNB in the Netherlands, where there is a low rate of neuraxial analgesia for labor and a low rate of CD.
Case 1-2024: A 25-Year-Old Pregnant Woman With Bleeding After a Snakebite
Authors: Fai KN , Moustafa H , Esso L , Boum Y
Published: August 2024

(N Engl J Med. 2024;390(2):166–173. doi: 10.1056/NEJMcpc2301033)

A case report of a 25-year-old pregnant woman with bleeding after a snakebite was presented as a special feature of the 100-year anniversary of the Case Records of the Massachusetts General Hospital.
Prenatal Care Utilization and Birth Outcomes After Expansion of the National Health Service Corps
Authors: Ma Yanlei , Baker Olesya , Zhang Fang , Cochran-McClain Carrie , Kaimal Anjali J. , Yu Hao
Published: August 2024

OBJECTIVE:

The National Health Service Corps (NHSC) attracts clinicians to Health Professional Shortage Areas (HPSAs) through scholarships and loan repayments. Since 2009, the NHSC workforce, including maternity care clinicians, has substantially expanded. This study evaluates the association between NHSC expansion and prenatal care and birth outcomes.

METHODS:

In this quasi-experimental study, we adopted a generalized difference-in-differences design to compare changes in prenatal care and birth outcomes from 2005 to 2019 using birth certificate data. Counties designated as HPSAs without any NHSC maternity care clinicians throughout the study period were control counties, and those without such clinicians before 2009 but receiving them after 2009 were treated counties. Outcome measures include a count variable of number of prenatal visits and four dichotomous variables: prenatal care initiation in the first trimester, adequacy of prenatal care, preterm birth, and low birth weight. We estimated negative binomial models for number of prenatal visits and linear probability models for the dichotomous outcomes, adjusting for maternal characteristics, non-NHSC clinician density, and state-level policies. Stratified analyses were also conducted on the basis of birthing people's demographics and county-level characteristics.

RESULTS:

Our sample comprised 12,980,111 live births between 2005 and 2019 by individuals residing in 1,254 HPSA counties without any NHSC maternity care clinicians before 2009, including 222 counties that received such clinicians after 2009. Compared with control counties, pregnant people in treated counties experienced significant increases in prenatal visits (211 more prenatal visits relative to baseline of 11,226 visits per 1,000 births, P<.001) and in the likelihood of receiving adequate prenatal care (1.43 percentage point increase relative to baseline of 67.0 percentage points, P<.01). Although the NHSC expansion improved prenatal care use for all racial and ethnic groups, pregnant people residing in urban and high social vulnerability areas benefited most. Improvements in birth outcomes were observed only among certain subgroups such as a 0.91 percentage point reduction in preterm birth (relative to baseline of 12.6 percentage points, P<.001) and a 0.87 percentage point reduction in low birth weight (relative to baseline of 8.2 percentage points, P<.05) among pregnant people living in full-county HPSAs.

CONCLUSION:

The NHSC expansion since 2009 was associated with increases in prenatal care utilization, particularly among vulnerable populations. Although improvements were not observed in birth outcomes overall with NHSC expansion, modest reductions were observed in preterm birth and low birth weight in subsets of the population.
Intradermal Botulinum Toxin A on Skin Quality and Facial Rejuvenation: A Systematic Review and Meta-analysis
Authors: Rahman Eqram , Rao Parinitha , Philipp-Dormston Wolfgang , Webb William Richard , Garcia Patricia E. , Ioannidis Sotirios , Kefalas Nicola , Kajaia Albina , Friederich Lisa , Yu Nanze , Wang Keming , Parikh Apul , Almeida Ada R.T. , Carruthers Jean D.A. , Carruthers Alastair , Mosahebi Ash , Wu Woffles , Goodman Greg
Published: August 2024

Background:

Botulinum toxin A (BTxA) has gained popularity as a nonsurgical aesthetic treatment for skin rejuvenation. However, previous studies on intradermal BTxA have shown inconsistent results. This systematic review and meta-analysis with trial sequential analysis aimed to assess the efficacy and safety of intradermal BTxA for facial rejuvenation.

Methods:

Following PRISMA guidelines, a comprehensive search was conducted in various databases from January 2008 to March 2023. Outcome measures included sebum production, pore size, skin hydration, skin texture, erythema index, facial wrinkles, and facelift. Eligible studies included human-based clinical trials and prospective cohort studies published in English, focusing on healthy populations requiring facial rejuvenation. Two authors independently screened the titles and abstracts, followed by a full-text review to determine study eligibility. Data extraction and quality assessment were performed by two authors using predefined criteria.

Results:

Ten studies met the inclusion criteria, including five randomized controlled trials and five prospective cohort studies with 153 participants. Studies revealed positive effects of intradermal BTxA on various outcome measures related to facial rejuvenation. These effects included improvements in sebum production, pore size, erythema index, facial wrinkles, skin texture and elasticity, and overall facelift but not skin hydration. All failed to reach the required information size in the trial sequential analysis.

Conclusions:

Findings suggest positive outcomes in multiple attributes of skin quality and facial rejuvenation. However, more high-quality research is needed to establish definitive conclusions. These findings contribute to the evidence base for nonsurgical aesthetic treatments, emphasizing the importance of ongoing research in this field.
Late-onset Total Necrosis in Deep Inferior Epigastric Perforator Flap after Contrast Enhanced Computed Tomography
Authors: Maitani Kosuke , Tomita Koichi , Kitamura Natsuko , Kadowaki Miki , Kubo Tateki
Published: August 2024

There seems to be an incessant debate regarding the duration of dependency of free flaps on pedicle vessels and the extent to which neovascularization from surrounding tissue contributes to the fortification of the free flaps. Although animal studies have suggested that pedicle vessels can be safely divided 5–8 days postoperatively without flap failure in fasciocutaneous flaps, recent clinical reports, particularly concerning the deep inferior epigastric perforator (DIEP) flap, cast doubt on this assumption. This report highlights a singular case of delayed-onset total necrosis in a DIEP flap following a contrast enhanced computed tomography (CECT) scan conducted 48 days post reconstructive surgery. The patient, a 56-year-old woman, had undergone a mastectomy for right breast cancer followed by immediate tissue expander placement. Subsequently, 6 months later, she underwent delayed reconstructive surgery with a DIEP flap. The postoperative course was uneventful, except that she had a CECT scan as part of follow-up care 48 days postoperatively and developed an abrupt yellow exudate from the right breast wound 2 days later, eventually leading to aggressive debridement of the totally necrotized flap 60 days postoperatively. This case marks the first instance of late-onset total necrosis of a DIEP flap following a CECT. The intensified endothelial damage induced by contrast media, in the context of the high dependency of the DIEP flap on the pedicle vessels with marginal blood supply from the surrounding wound bed, could be ascribed as the cause of this total loss of the flap.
A Composite Application Technique of Single-stage Dermal Templates to Improve Handling and Ease of Use
Authors: Maitz Joanneke , Carelli Lucas G. , Coady Elizabeth , Loi Duncan , Maitz Peter
Published: August 2024

The “work horse” for the treatment of full-thickness defects of any etiology, including chronic nonhealing wounds and traumatic injuries, is generally autologous split-thickness skin grafts (STSGs), meshed, hand-fenestrated, or a sheet graft. Advancements in skin tissue engineering have allowed for the integration of dermal substitutes to be combined with autologous STSGs, adding valuable options for restoring the skin’s complex multilayered structure. Although dermal templates offer a promising avenue for more nuanced reconstruction in certain cases, their application is not without challenges, particularly when they are made from delicate materials. The following technique simplifies the application technique of single-stage dermal templates by using a composite approach. To demonstrate this technique, MatriDerm, a 1-mm-thick bovine collagen-elastin dermal template, is used to enable an STSG to be applied in a one-stage procedure.
SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY INSIGHTS INTO IDIOPATHIC EPIRETINAL MEMBRANE SURGERY OUTCOMES
Authors: Mansilla Raquel , Bande Manuel F. , Mera Purificación , Ruiz-Oliva Francisco , Marticorena Joaquin , Blanco-Teijeiro María José
Published: August 2024

Purpose:

The aim of this study is to assess the prognostic value of a classification system that includes the presence of ectopic inner foveal layers and other anatomical variables identified in spectral-domain optical coherence tomography for idiopathic epiretinal membrane (ERM) surgery.

Methods:

A descriptive-analytic, longitudinal, retrospective study was conducted on patients with idiopathic ERMs treated with pars plana vitrectomy from January 2017 to December 2021. Clinical data and spectral-domain optical coherence tomography images were reviewed presurgery and 12 months postsurgery. The primary outcome measured was best-corrected visual acuity (BCVA) before and after surgery, analyzing the impact of anatomical factors on BCVA in patients undergoing ERM surgery.

Results:

This study included 342 eyes from 323 patients. Postsurgical evaluations showed significant reductions in central foveal thickness across all ERM stages, with most Stage 4 ERMs regressing to Stage 3. The mean improvement in BCVA was significant for all stages, with earlier stages showing better results. The presence of macular edema and ellipsoid zone disruption were significant predictors of postsurgical BCVA, while disorganization of the retinal inner layer showed an association with visual recovery but was not conclusively predictive.

Conclusion:

This study highlights the importance of spectral-domain optical coherence tomography in assessing retinal changes in idiopathic ERMs, demonstrating the prognostic value of ectopic inner foveal layers stage scheme and other anatomical variables such as ellipsoid zone disruption and macular edema presence on BCVA. These findings offer insights into surgical prognostication and the potential for personalized treatment strategies.
Analysis of Corneal Phenotypes in Japanese Patients With Myotonic Dystrophy Type 1
Authors: Kubo Kenya , Oie Yoshinori , Koto Ryota , Nishida Nozomi , Kai Chifune , Maeno Sayo , Kubota Tomoya , Nakamori Masayuki , Takahashi Masanori P. , Tsujikawa Motokazu , Nishida Kohji
Published: August 2024

Purpose:

To analyze the corneal phenotypes of Japanese patients with myotonic dystrophy type 1 (DM1).

Methods:

We included patients with DM1 who were diagnosed with clinical neuromuscular symptoms by neurologists and CTG trinucleotide repeat (TNR) expansion of the (myotonic dystrophy protein kinase)DMPKgene. We analyzed the corneal phenotype using slit-lamp examination, specular microscopy, and anterior segment optical coherence tomography. We evaluated TNR expansion in theTCF4gene of leukocyte-derived genomic DNA by fragment analysis using polymerase chain reaction and triplet-repeat primed polymerase chain reaction.

Results:

Nineteen eyes from 10 patients with DM1 (DM1 group) and 72 eyes from 37 healthy participants (control group) were analyzed. The average age was 49.3 ± 11.9 and 51.8 ± 12.9 years in the DM1 and control groups, respectively (P= 0.11). Slit-lamp examination demonstrated that 2 patients with DM1 had bilateral corneal guttae equivalent to modified Krachmer grade 1 of Fuchs endothelial corneal dystrophy. Dark areas on specular microscopy were observed in 4 of 19 eyes (21.1%) and 0 of 72 eyes (0%) in the DM1 and control groups, respectively, with statistically significant differences (P= 0.002). The average endothelial cell density in the DM1 group (3536 ± 722 cells/mm2) was significantly higher than that in the control group (3026 ± 412 cells/mm2) (P= 0.0006). TNR expansion inTCF4was not detected in eyes with corneal guttae or in the dark areas in the DM1 group.

Conclusions:

Japanese patients with DM1 without TNR expansion inTCF4have a mild phenotype equivalent to Fuchs endothelial corneal dystrophy. Endothelial cell density is higher in DM1 patients than in normal participants.
Influence of endovascular surgery on abdominal aortic aneurysm management strategies from a national health insurance database survey
Authors: Chen Wei-Ling , Kan Chung-Dann , Huang Yi-Ting , Shih Hsin-I
Published: August 2024

Background:

Abdominal aortic aneurysm (AAA) is a significant global health concern, yet comprehensive population-based studies remain limited. This study aimed to evaluate the hospitalization rates, surgical trends, mortality, and reintervention rates for ruptured (r-AAA) and nonruptured (nr-AAA) AAA using data from a national health insurance database.

Methods:

A population-based retrospective cohort study was conducted utilizing data from the Taiwanese National Health Insurance Research Database from 2007 to 2018. The study included individuals aged 20 years and older with a newly diagnosed AAA.

Results:

Among 70 457 patients diagnosed with aortic aneurysm or dissection, 22 538 (32%) adult patients (≥20 years) were identified with AAA. The annual incidence of AAA ranged from 7.7 to 10.3 per 100 000 population, with r-AAA decreasing from 1.3 to 0.8 per 100 000 and nr-AAA from 9.0 to 6.8 per 100 000. Most patients with AAA were older adults (85%), with 15 392 (68%) hospitalized and 4885 (32%) undergoing surgery within 14 days of diagnosis. The use of endovascular aneurysm repair (EVAR) significantly increased from 28% to 96% over the study period. Long-term survival was higher in patients who underwent open surgical repair (OSR) compared to those who received EVAR or conservative management, irrespective of whether they had r-AAA or nr-AAA.

Conclusion:

AAA predominantly affects older individuals, and the annual incidence shows a declining trend. Since the introduction of EVAR, its use has steadily increased while OSR rates have decreased. Although both EVAR and OSR are associated with reduced mortality in patients with r-AAA, OSR is linked to superior long-term survival outcomes.
The Effect of Sport Specialization on Injury Risk in NCAA Athletes: Results From the SAFE Consortium
Authors: Lutsic Jared J. , Lutsic Seth E. , Ibrahim David S. , Augusta Matthew C. , Robinson Jason D. , Tong Kevin M. , Saffarian Mathew R. , Nogel Sally E. , Fitton Nathan J.
Published: August 2024

Objective:

Youth athletes are beginning to specialize in a single sport more often. Previous studies in sports medicine and orthopedics have shown an association between intensity of sport specialization and incidence of injuries. This study is the first of its kind to explore the effects of early sport specialization on injury risk through a multicenter framework with a concentration on NCAA athletics.

Design:

Retrospective cohort study.

Setting:

SAFE Consortium.

Participants:

A total of 211 collegiate athletes from the NCAA's 3 levels of competition: Division I, II, and III. Data were collected by the SAFE investigators.

Intervention:

N/A.

Main Outcome Measures:

Participants completed a questionnaire about their demographics, sport participation, specialization status, physical injuries, recovery period, and treatment method. Specialization status was calculated with a previously published 3-point scale: low, moderate, and high. Injuries were categorized as upper extremity injuries (UEIs) and lower extremity injuries (LEIs).

Results:

Highly specialized athletes were more likely to report UEIs and LEIs than low specialized athletes (P < 0.0001). Moderate specialization, in contrast to low specialization, was associated with a higher likelihood of LEIs (P = 0.03) but not UEIs (P = 0.052). Highly specialized athletes were more likely to report an injury of any kind.

Conclusions:

The SAFE investigators found high specialization was associated with a history of UEIs and LEIs. Return to play was longer for highly specialized athletes versus low specialized athletes (112 days and 85 days, respectively). Highly specialized athletes were more likely to be from Division I and to require surgery.
Ticagrelor monotherapy after short duration of dual antiplatelet therapy compared to continued dual antiplatelet therapy in patients with acute coronary syndromes undergoing percutaneous coronary interventions: an updated meta-analysis
Authors: Mansuri Zeeshan , Ashraf Hadiah , Taikadan Thahsin , Rajith Gokul , Ayesha Ayesha , Fatima Urooj , Erzinger Gabriel
Published: August 2024

Background

The optimum duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) remains controversial. Ticagrelor monotherapy after short duration of DAPT (1–3 months) is a subject of research. We conducted an updated systematic review and meta-analysis comparing the ticagrelor monotherapy with continued DAPT after short duration of DAPT in patients with ACS undergoing PCI.

Methods

PubMed, Embase, and Cochrane databases were searched for studies comparing ticagrelor monotherapy to DAPT after PCI and reported the outcomes of major adverse cardiovascular and cerebrovascular events (MACCE); net adverse clinical events (NACE); myocardial infarction (MI); major bleeding; death from any cause; definite or probable stent thrombosis; and target vessel revascularization (TVR). Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Statistical analysis was performed using Review Manager (Cochrane collaboration). Heterogeneity was examined with I
2 test.

Results

Of 3,208 results, five studies with 21,407 patients were included of which 50% received ticagrelor monotherapy. Studies had reported follow up of 12 months. Major bleeding [hazard ratio 0.47; 95% confidence interval (CI), 0.37–0.61; P < 0.001], NACE (hazard ratio 0.71; 95% CI, 0.56–0.90; P = 0.005), and all-cause death (hazard ratio 0.76; 95% CI, 0.59–0.98; P = 0.04) were significantly less with ticagrelor monotherapy. Other outcomes were comparable in both groups.

Conclusion

In patients with ACS undergoing PCI, ticagrelor monotherapy reduces major bleeding, NACE and all-cause death as compared to continued DAPT for 12 months. Major ischemic outcomes were similar. Ticagrelor monotherapy is the way forward after short duration of DAPT after PCI in ACS.
How Can “No Specific Molecular Profile” Heterogeneity be Reduced in Molecularly Classified Endometrial Cancer?: Prognostic Significance of L1 Cell Adhesion Molecule
Authors: Ozdemir Cem Yagmur , Arioz Dagistan Tolga , Pektaş Mine Kanat , Ozdemir Cigdem , Cicekli Nayif , Bilir Filiz , Dur Riza , Goztepe Ecenur
Published: August 2024

This study aims to investigate the role of L1 cell adhesion molecule (L1CAM) in the prognostic assessment of endometrial cancers that have been depicted as having no specific molecular profile (NSMP) in molecular classification. This is a retrospective review of 150 patients who received the diagnosis of endometrial cancer and underwent surgery at the study center between January 2008 and January 2022. When evaluating L1CAM immunohistochemical staining, scoring was done according to the percentage of positivity in tumor cells. Accordingly, score 0 = 0%, score 1=1% to 10%, score 2 = >10% to 50% and score 3 = >50%. If the staining in tumor cells was ≥10% (scores 2 and 3), it was considered positive. The patients with L1CAM positivity had significantly more frequent lymphovascular space invasion and lymph node metastasis than patients with L1CAM negativity (P = 0.013 and P = 0.007). L1CAM expression was strongly associated with mutant p53 (P = 0.003). Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with L1CAM positivity (P = 0.001 for both). Seventy-nine patients (52.7%) were put into NSMP group. About 84.8% of them (n = 67) were L1CAM negative and 15.2% of them (n = 12) were L1CAM-positive. Recurrence was significantly higher (P = 0.001) and overall survival and progression-free survival were significantly lower in patients with NSMP who were positive for L1CAM (P = 0.002 and P = 0.001, respectively). This study demonstrates that L1CAM expression status may add prognostic information to endometrial cancer, particularly in the NSMP subgroup. Considering the prognostic importance of L1CAM, its use as a marker may make significant contributions to reducing prognostic heterogeneity, especially in the NSMP subgroup.
Nonsclerotic Lichen Sclerosus of Vulva: A Clinicopathologic Analysis
Authors: Bartels Anne K. , Fadare Oluwole
Published: August 2024

The International Society of the Study of Vulvovaginal Diseases (ISSVD) recently defined nonsclerotic lichen sclerosus (NSLS) as a scenario wherein the clinical findings are consistent with lichen sclerosus (LS), but no microscopic evidence of dermal sclerosis is found and recognized 4 histologic subcategories. Herein, we present an institutional experience with NSLS, with an emphasis on frequency, application of the ISSVD categories in routine practice, and clinicopathologic correlation. The authors reviewed clinical and pathologic findings for consecutive vulvar biopsies in which LS was a clinical and/or pathologic consideration. Cases were classified as classical/sclerotic LS (CLS), NSLS (per ISSVD criteria), and “unclassified,” the latter of which were cases not classifiable as NSLS or CLS, despite a clinical impression or LS or LS being a significant clinical consideration (ie, “clinical LS”). In clinical LS cases, CLS and NSLS were diagnosed histologically in 61% (182/298) and 15% (44/298), respectively, whereas the remainder were histologically unclassified. The latter group was microscopically heterogeneous, devoid of a consistent pathologic profile, and generally showed absence, focality, minimality, ambiguity, or infrequency of features that would have allowed their categorization into one of the NSLS categories. Among the 4 categories for the categorizable NSLS cases, the “lichenoid dermatitis” pattern (61.4%) was the commonest, followed by dermal fibrosis with acanthosis (22.7%), dermal fibrosis without acanthosis (9.1%), and hypertrophic lichenoid dermatitis (6.8%). The clinical response rates to topical therapies for the NSLS and unclassified groups were 71% and 62%, respectively (P=0.4). Our findings highlight the significance of clinicopathologic correlation in the diagnosis of NSLS. In the setting of clinical LS, some histologic evidence to support that impression is found in most cases when the ISSVD system for diagnosis and classification of biopsies is applied. However, a subset of clinical LS cases are not pathologically classifiable as either CLS or any of the NSLS categories; these display nonspecific histologic features and require future study.
Life and Death 2
Authors: Bhatia Ishan , Brandmeir Nicholas
Published: August 2024

Summary Statement

Life and Death 2: The Brain was the first computerized neurosurgical simulator. It was developed as a commercial video game for a general audience. Despite this, it contains many valuable lessons for the simulation and education of nontechnical skills as well as being a historical landmark in the field of neurosurgery and medical simulation.
Outcomes of Liver Transplantation From Hepatitis C Virus–positive DCD Donors and Its Utilization Among Centers in the United States
Authors: Punjala Sai Rithin , Logan April J. , Subramanian Jayanthan , Von Stein Lauren , Limkemann Ashley , Al-Ebrahim Musab , Black Sylvester , Schenk Austin D. , Washburn William K. , Singh Navdeep
Published: August 2024

Background.

Donation after circulatory death (DCD) or hepatitis C virus (HCV+) liver grafts are underused among transplant centers in the United States. The study aimed to evaluate organ utilization and outcomes of liver grafts from DCD donors with HCV infection.

Methods.

National registry and local center data of all deceased donor liver transplants performed between November 2016 and December 2021 were analyzed. All transplants were divided into 4 groups: HCV– DCD, HCV– donation after brain death [DBD], HCV+ DCD, and HCV+ DBD. The outcome of interest was 1-y graft survival.

Results.

Out of 146 liver transplant centers in the United States, liver transplants were not performed from DCD donors, HCV+ donors, and a combination of DCD and HCV+ donors by 28.7%, 27%, and 70%–72% of centers, respectively. In multivariate analysis, increasing center acceptance ratio was associated with increased utilization of liver grafts from DCD HCV– and DCD HCV antibody-positive nucleic acid test negative donors. Nationally, 1-y graft survival of HCV– DCD liver grafts was lower compared with other groups (89% versus 92% HCV+ DCD versus 93% HCV+ DBD versus 92% HCV– DBD, log rank P < 0.0001). There was no difference in 1-y graft survival among groups locally.

Conclusions.

Liver grafts from HCV+ DCD donors have 1-y patient and graft survival comparable with DBD liver grafts from donors with or without HCV infection. These results encourage the widespread use of liver grafts from DCD and HCV+ donors and standardization of practice in DCD donation to expand the donor pool without compromising short-term outcomes.
Asian Cohort for Alzheimer Disease (ACAD) Pilot Study
Authors: Peavy Guerry M. , Võ Namkhuê , Revta Carolyn , Lu Anna T. , Lupo Jody-Lynn , Nam Percival , Nguyễn Khải H. , Wang Li-San , Feldman Howard H.
Published: August 2024

Introduction:

The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD).

Methods:

Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs).

Results:

Twenty-five participants completed the study (mean age=73.8 y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF.

Discussion:

This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study.
Does Mild Functional Impairment Predict Dementia in Older Adults With Normal Cognition?
Authors: Zhang Lei Lei , Numbers Katya , Brodaty Henry , Lam Ben C.P. , Mahalingam Gowsaly , Reppermund Simone
Published: August 2024

Objectives:

Functional impairment can be an early indicator of cognitive decline. However, its predictive utility in cognitively normal (CN) older adults remains unclear. This study aimed to determine whether mild functional impairment (MFI) in CN older adults could predict incident dementia over 6 years, in addition to assessing its association with cognitive performance.

Design:

A longitudinal study with a 6-year follow-up.

Participants:

A cohort of 296 community-dwelling CN older adults.

Measurements:

MFI was defined by cutoffs for impairment on an objective performance-based and/or subjective questionnaire-based functional assessment. Cox regression analysis was conducted to assess the relationship between MFI and risk of incident dementia and cognitive performances over 6 years. Linear regression analysis examined the association between MFI and baseline cognitive performance.

Results:

There were no significant longitudinal associations between MFI and incident dementia or changes in cognitive performance over 6 years. Defining MFI using both performance-based and informant-reported assessments was predictive of dementia. Cross-sectional analyses demonstrated significant associations between MFI and poorer baseline global cognition and performance in attention, visuospatial ability, and executive functioning.

Conclusions:

CN older adults with MFI were not at an increased risk of developing dementia over 6 years. A definition of functional impairment requiring both performance-based and informant-based assessments may be useful in predicting dementia.
Examining the complex dynamics influencing acute malnutrition in Turkana and Samburu counties: study protocol
Authors: Wilunda Calistus , Sidze Estelle , Thuita Faith , Amugsi Dickson , Abajobir Amanuel , Mutua Martin , Mwangi Bonventure , Iddi Samuel , Lutter Chessa , Flax Valerie , Webale Albert , Anono Esther , Odhiambo Hazel , Wainaina Caroline Wangui , Kimani-Murage Elizabeth , Ekiru Stephen , Chepkwony Gillian , Ebei John , Lesiamito Duncan , Sagara Brad
Published: August 2024

Acute malnutrition in children under 5 years is persistent in Eastern Africa’s arid and semi-arid lands. This study aimed to identify the drivers of acute malnutrition in Turkana and Samburu counties, Kenya. This was a population-based longitudinal mixed-methods observational study. Qualitative and quantitative data were collected at Wave 1 but only quantitative data were collected during follow-up. Participants were a representative sample of children and their primary caregivers from households with children under 3 years at Wave 1. Anthropometric measurements of all children under 5 years in the sampled households were taken at Wave 1 (May to July 2021), and one child under 3 years was randomly selected for follow-up about every 4 months over 2 years for six data collection waves. The study also collected data on socio-demographics; child feeding practices and morbidity, household water and food insecurity; shocks; coping strategies, social safety nets and economic safeguards; water, sanitation, and hygiene; women’s decision making; and food consumption. Qualitative data were collected through community dialogues, focus group discussions, in-depth interviews, photovoice and key informant interviews with mothers and fathers with children under 5 years, community leaders, county officials and staff of nongovernmental organizations. The data were coded and analyzed thematically. Data collection is complete, and analysis is ongoing. The analysis includes thematic analysis of qualitative data and descriptive and multivariable regression analysis of quantitative data.
Respiratory virus detection and sequencing from negative SARS-CoV-2 rapid antigen tests
Authors: Jules Emmanuela , Decker Charlie , Bixler Brianna Jeanne , Ahmed Alaa , Zhou Zijing (Carol) , Arora Itika , Tafesse Henok , Dakanay Hannah , Bombin Andrei , Wang Ethan , Ingersoll Jessica , Bifulco Kathy , Frediani Jennifer K. , Parsons Richard , Sullivan Julie , Greenleaf Morgan , Waggoner Jesse J. , Martin Greg S. , Lam Wilbur A. , Piantadosi Anne
Published: August 2024

Genomic epidemiology offers important insight into the transmission and evolution of respiratory viruses. We used metagenomic sequencing from negative SARS-CoV-2 antigen tests to identify a wide range of respiratory viruses and generate full genome sequences, offering a streamlined mechanism for broad respiratory virus genomic surveillance.
Enhanced metagenomics-enabled transmission inference with TRACS
Authors: Tonkin-Hill Gerry , Shao Yan , Zarebski Alexander E. , Mallawaarachchi Sudaraka , Xie Ouli , Mäklin Tommi , Thorpe Harry A. , Davies Mark R. , Bentley Stephen D. , Lawley Trevor D. , Corander Jukka
Published: August 2024

Coexisting strains of the same species within the human microbiota pose a substantial challenge to inferring the host-to-host transmission of both pathogenic and commensal microbes. Here, we present TRACS, a highly accurate algorithm for estimating genetic distances between strains at the level of individual SNPs, which is robust to intra-species diversity within the host. Analysis of well-characterised Faecal Microbiota Transplantation datasets, along with extensive simulations, demonstrates that TRACS substantially outperforms existing strain aware transmission inference methods. We use TRACS to infer transmission networks in patients colonised with multiple strains, including SARS-CoV-2 amplicon sequencing data from UK hospitals, deep population sequencing data ofStreptococcus pneumoniaeand single-cell genome sequencing data from malaria patients infected withPlasmodium falciparum. Applying TRACS to gut metagenomic samples from a large cohort of 176 mothers and 1,288 infants born in UK hospitals revealed species-specific transmission rates between mothers and their infants. Notably, TRACS identified increased persistence ofBifidobacterium brevein infants, a finding missed by previous analyses due to the presence of multiple strains.
Gluteus Medius Muscle Activation Patterns during Gait with Cerebral Palsy (CP): A hierarchical clustering analysis
Authors: Davoudi Mehrdad , Salami Firooz , Reisig Robert , Gather Katharina Susanne , Wolf Sebastian I.
Published: August 2024

Duchenne gait, characterized by an ipsilateral trunk lean towards the affected stance limb, compensates for weak hip abductor muscles, notably the gluteus medius (GM). This study aims to investigate how electromyographic (EMG) cluster analysis of GM contributes to a better understanding of Duchenne gait in patients with cerebral palsy (CP). We analyzed retrospective gait data from 845 patients with CP and 65 typically developed individuals. EMG activity of GM in envelope format were collected and examined with gait kinematics and kinetics parameters in frontal plane and hip abductor strength, and hip abduction passive range of motion.

Six key EMG envelope features during ten gait phases were extracted and normalized. A hybrid K-means-PSO clustering algorithm was employed, followed by hierarchical clustering. The identified clusters were characterized by having a low (cluster_1), medium (cluster_2), and high (cluster_3) activity of GM during loading response. The patients in cluster_1 also exhibited pathological gait characteristics, including increased trunk lateral lean and weak hip abductor, which are associated with Duchenne gait. The patients in this cluster were subclustered according to their response to the intervention: SUB_1 with a significant improvement in trunk obliquity, pelvic obliquity, and hip abduction after intervention, and SUB_2 without such improvement. Comparing pre-treatment EMG and clinical exam of the sub_clusters, SUB_1 had significantly higher activity of GM during 50-87% of the gait cycle with a greater passive range of hip abduction compared to SUB_2. This study established a relationship between EMG of GM and frontal plane gait abnormalities in patients with CP, highlighting potential improvement in Duchenne gait with prolonged GM activity during swing after the intervention.
NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion
Authors: Taghavi Amirhossein , Chen Jonathan L. , Wang Zhen , Sinnadurai Krishshanthi , Salthouse David , Ozon Matthew , Feri Adeline , Fountain Matthew A. , Choudhary Shruti , Childs-Disney Jessica L. , Disney Matthew D.
Published: August 2024

RNA repeat expansions fold into stable structures and cause microsatellite diseases such as Huntington’s disease (HD), myotonic dystrophy type 1 (DM1), and spinocerebellar ataxias (SCAs). The trinucleotide expansion of r(CAG), or r(CAG)exp, causes both HD and SCA3, and the RNA’s toxicity has been traced to its translation into polyglutamine (polyQ; HD) as well as aberrant pre-mRNA alternative splicing (SCA3 and HD). Previously, a small molecule,1, was discovered that binds to r(CAG)expand rescues aberrant pre-mRNA splicing in patient-derived fibroblasts by freeing proteins bound to the repeats. Here, we report the structures of single r(CAG) repeat motif (5’CAG/3’GAC where the underlined adenosines form a 1×1 nucleotide internal loop) in complex with1and two other small molecules via nuclear magnetic resonance (NMR) spectroscopy combined with simulated annealing. Compound2was designed based on the structure of1bound to the RNA while3was selected as a diverse chemical scaffold. The three complexes, although adopting different 3D binding pockets upon ligand binding, are stabilized by a combination of stacking interactions with the internal loop’s closing GC base pairs, hydrogen bonds, and van der Waals interactions. Molecular dynamics (MD) simulations performed with NMR-derived restraints show that the RNA is stretched and bent upon ligand binding with significant changes in propeller-twist and opening. Compound3has a distinct mode of binding by insertion into the helix, displacing one of the loop nucleotides into the major groove and affording a rod-like shape binding pocket. In contrast,1and2are groove binders. A series of single molecule magnetic force spectroscopy studies provide a mechanistic explanation for how bioactive compounds might rescue disease-associated cellular phenotypes.

Graphical Abstract
Transcriptomic profiling of gill biopsies to define predictive markers for seawater survival in farmed Atlantic salmon
Authors: Grønvold Lars , van Dalum Mattis J. , Striberny Anja , Manousi Domniki , Ytrestøyl Trine , Mørkøre Turid , Boison Solomon , Gjerde Bjarne , Jørgensen Even , Sandve Simen R. , Hazlerigg David G.
Published: August 2024

Wild Atlantic salmon migrate to sea following completion of a developmental process known as parr - smolt transformation (PST), which establishes a seawater (SW) tolerant phenotype. Effective imitation of this aspect of anadromous life-history is a crucial aspect of commercial salmon production, with current industry practice being marred by significant losses during transition from the freshwater (FW) to SW phase of production. The natural photoperiodic control of PST can be mimicked by exposing farmed juvenile fish to a reduced duration photoperiod for at least 6 weeks before increasing the photoperiod in the last 1 - 2 months before SW transfer. While it is known that variations in this general protocol affect subsequent SW performance, there is no uniformly accepted industry standard; moreover, reliable prediction of SW performance from fish attributes in the FW phase remains a major challenge. Here we describe an experiment in which we took gill biopsies 1 week prior to SW transfer from 3000 individually tagged fish raised on 3 different photoperiod regimes during the FW phase. Biopsies were subjected to RNA profiling by Illumina sequencing, while individual fish growth and survival was monitored over 300 days in a SW cage environment, run as a common garden experiment. Using a random forest machine learning algorithm, we developed gene expression-based predictive models for initial survival and stunted growth in SW. Stunted growth phenotypes could not be predicted based on gill transcriptomes, but survival the first 40 days in SW could be predicted with moderate accuracy. While several previously identified marker genes contribute to this model, a surprisingly low weighting is ascribed to sodium potassium ATPase subunit genes, contradicting advocacy for their use as SW readiness markers. However, genes with photoperiod-history sensitive regulation were highly enriched among the genes with highest importance in the prediction model. This work opens new avenues for understanding and exploiting developmental changes in gill physiology during smolt development.