bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes and Complications in Management of Congenital Myopathy Early-Onset Scoliosis
Authors: Magee Lacey , Bram Joshua T. , Anari Jason B. , Ramo Brandon , Mayer Oscar H. , Matsumoto Hiroko , Brooks Jaysson T. , Andras Lindsay , Lark Robert , Fitzgerald Ryan , Truong Walter , Li Ying , Karlin Lawrence , Schwend Richard , Weinstein Stuart , Roye David , Snyder Brian , Flynn John M. , Oetgen Matthew , Smith John , Cahill Patrick J.
Published: July 2021

Background:

Congenital myopathies (CMs) are complex conditions often associated with early-onset scoliosis (EOS). The purpose of this study was to investigate radiographic outcomes in CM patients undergoing EOS instrumentation as well as complications. Secondarily, we sought to compare these patients to a population with higher prevalence, cerebral palsy (CP) EOS patients.

Methods:

This is a retrospective study of a prospectively collected multicenter registry. The registry was queried for EOS patients with growth-sparing instrumentation (vertical expandable prosthetic titanium ribs, magnetically controlled growing rods, traditional growing rod, or Shilla) and a CM or CP diagnosis with minimum 2 years follow-up. Outcomes included major curve magnitude, T1-S1 height, kyphosis, and complications.

Results:

Sixteen patients with CM were included. Six (37.5%) children with CM experienced 11 complications by 2 years. Mean major curve magnitude for CM patients was improved postoperatively and maintained at 2 years (P<0.01), with no significant increase in T1-S1 height or maximum kyphosis(P>0.05). Ninety-seven patients with CP EOS were included as a comparative cohort. Fewer CP patients required baseline respiratory support compared with CM patients (20.0% vs. 92.9%, P<0.01). Fifty-four (55.7%) CP patients experienced a total of 105 complications at 2 years. There was no evidence that the risk of complication or radiographic outcomes differs between cohorts at 2 years, though CP EOS patients experienced significant improvement in all measurements at 2 years.

Conclusions:

EOS CM children face a high risk of complication after growing instrumentation, with similar curve correction and risk of complication to CP patients.

Level of Evidence:

Level III.
Ergonomics in Spine Surgery
Authors: Kolz Joshua M. , Wagner Scott C. , Vaccaro Alexander R. , Sebastian Arjun S.
Published: July 2021

As physician burnout and wellness become increasingly recognized as vital themes for the medical community to address, the topic of chronic work-related conditions in surgeons must be further evaluated. While improving ergonomics and occupational health have been long emphasized in the executive and business worlds, particularly in relation to company morale and productivity, information within the surgical community remains relatively scarce. Chronic peripheral nerve compression syndromes, hand osteoarthritis, cervicalgia and back pain, as well as other repetitive musculoskeletal ailments affect many spinal surgeons. The use of ergonomic training programs, an operating microscope or exoscope, powered instruments for pedicle screw placement, pneumatic Kerrison punches and ultrasonic osteotomes, as well as utilizing multiple surgeons or microbreaks for larger cases comprise several methods by which spinal surgeons can potentially improve workspace health. As such, it is worthwhile exploring these areas to potentially improve operating room ergonomics and overall surgeon longevity.
Intravenous immunoglobulin efficacy on pembrolizumab induced severe toxic epidermal necrolysis
Authors: Kian Waleed , Zemel Melanie , Elobra Firas , Sharb Adam A. , Levitas Dina , Assabag Yarden , Alguayn Farouq , Yakobson Alexander , Rouvinov Keren , Fuchs Lior
Published: July 2021

Pembrolizumab is an immune checkpoint inhibitor used in many different cancers. Several immune-related adverse events (irAEs) have been associated with pembrolizumab, including toxic epidermal necrolysis. Here, we are presenting a patient with non-small cell lung cancer that developed toxic epidermal necrolysis 3-days following initiation of pembrolizumab. Following high-dose steroid therapy, intravenous immunoglobulin 2 g/kg was initiated and resulted in complete resolution of all his irAEs. To our knowledge, this is the first reported case of total re-epithelialization and resolution of immune checkpoint inhibitor-induced toxic epidermal necrolysis following the use of intravenous immunoglobulin.
Treatment response to eribulin and anlotinib in lung metastases from rare perianal adenoid cystic carcinoma: a case report
Authors: Zheng Shengnan , Li Huiying , Lin Yongjuan , Xie Yu , Yin Zhenyu , Ge Weihong , Yu Tingting
Published: July 2021

Adenoid cystic carcinoma (ACC) is a rare salivary glands tumor and often displays aggressive behavior with frequent relapse and metastasis. The terminal ACC lacks standard treatment guidelines and is always accompanied by poor prognosis. Here, we report a case of rare perianal ACC who received resection and palliative adjuvant radiation. Five years later, PET-computed tomography (CT) showed perianal recurrence and multiple pulmonary metastases. Combined chemotherapy with doxorubicin, carboplatin and cyclophosphamide was applied for two cycles but ineffective. Further next-generation sequencing analysis of perianal tissue demonstrated the v-myb avian myelobastosis viral oncogene homolog and nuclear factor I/B fusion gene and two novel BCL-6 corepressor (BCOR) mutations (p.F1106Tfs*5 and p.L1524Hfs*8). The therapy was switched to eribulin and anlotinib and has been performed for eight cycles. At recent follow-ups, MRI and CT examinations revealed the diminishing perianal and pulmonary lesions. This study presented the first case of perianal ACC with multiple pulmonary metastases and particular BCOR mutations, who presented a durable response to eribulin and anlotinib, providing a potential therapeutic option for advanced refractory ACC.
Caregiver Perspectives on a Child's Diagnosis of 3q29 Deletion: “We Can't Just Wish This Thing Away”
Authors: Glassford Megan R. , Purcell Ryan H. , Pass Sarah , Murphy Melissa M. ,   The Emory 3q29 Project,*, Bassell Gary J. , Mulle Jennifer G.
Published: July 2021

Objective:

Genetic diagnoses are increasingly common in cases of intellectual disability and developmental delay. Although ascertainment of a relatively common, well-studied variant may provide guidance related to treatments and developmental expectations, it is less clear how the diagnosis of a rare variant affects caregivers, especially when the phenotype may include later-onset manifestations such as psychosis. In this study, we sought to identify caregiver concerns in the first qualitative study to assess the psychosocial impact of diagnosis on caregivers of individuals with 3q29 deletion syndrome (3q29Del), which is associated with a 40-fold increase in risk for psychosis.

Methods:

Participants were recruited from the national 3q29Del registry housed at Emory University (3q29deletion.org). Fifteen participants completed a semistructured phone interview during which they were asked about their experiences before, during, and after their child received a diagnosis of 3q29Del. Interview responses were analyzed using the general inductive approach, and overarching themes were identified.

Results:

We identified the following overarching themes: difficult “diagnostic odyssey,” mixed feelings about diagnosis, frustration with degree of uncertainty, and importance of resources. Importantly, our data suggest that future risk for psychosis is often not disclosed by medical professionals, consistent with the experience of individuals with 22q11.2 deletion syndrome.

Conclusions:

These results highlight potential gaps in how caregivers are informed of risk for adult-onset conditions and indicate key caregiver concerns for consideration in the diagnosis of 3q29Del.
Nonvitamin K Antagonist Oral Anticoagulant in Patients With Venous Thromboembolism and Polycythemia Vera or Essential Thrombocythemia: A Cohort Study
Authors: Weronska Anna , Papuga-Szela Elżbieta , Broniatowska Elzbieta , Undas Anetta
Published: July 2021

Thrombosis is the most common adverse event in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Little is known about the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with myeloproliferative neoplasms. We sought to evaluate the efficacy and safety of NOAC in a cohort of patients with PV and ET, who experienced venous thromboembolism (VTE). We enrolled 48 consecutive patients with PV (70.8%) and ET [median age 67.0 (interquartile range, 58.5–72.0) years], who experienced VTE. Patients received apixaban (39.6%), rivaroxaban (33.3%), or dabigatran (27.1%). During a median follow-up of 30 (interquartile range, 20.5–41.5) months, recurrent thrombotic events and bleeding were recorded. Four thrombotic events (3.3 per 100 patient-years) were reported. Three deep vein thrombosis episodes (2.5 per 100 patient-years) were experienced by 2 patients with PV, who received apixaban (5 mg bid) and dabigatran (150 mg bid), and 1 patient with ET, who received dabigatran (150 mg bid). One ischemic stroke occurred in a patient with PV on rivaroxaban (20 mg/d). There was 1 major bleeding (0.8 per 100 patient-years) in a patient with ET on dabigatran (150 mg bid) and 3 clinically relevant nonmajor bleeding (2.5 per 100 patient-years): 2 on rivaroxaban (20 mg/d) and 1 on apixaban (5 mg bid). We did not observe significant differences related to the type of NOAC. Three deaths (2.5 per 100 patient-years) unrelated to either VTE or bleeding were recorded. This study shows that NOACs may be effective and safe as secondary prevention of VTE in patients with myeloproliferative neoplasms.
Effects of Statins After Transcatheter Aortic Valve Implantation in Key Patient Populations
Authors: Fischer-Rasokat Ulrich , Renker Matthias , Bänsch Celine , Weferling Maren , Liebetrau Christoph , Herrmann Eva , Liakopoulos Oliver , Choi Yeong-Hoon , Hamm Christian W. , Kim Won-Keun
Published: July 2021

Statin therapy after transcatheter aortic valve replacement (TAVI) is associated with better short-term and long-term outcomes. It is of interest to identify specific patient populations that may profit from statin therapy. In this retrospective, observational analysis of 2862 patients with symptomatic aortic stenosis after successful transfemoral TAVI, survival during a three-year observation period was characterized by Kaplan–Meier analyses according to statin therapy. Hazard ratios and potential interactions for specific subgroups of patients were determined by Cox regression analyses. At hospital discharge 1761 patients were on low-intensity or moderate-intensity statins, 246 patients were on high-intensity statins, and 855 patients did not take statins. Statin therapy adherence during the first 3 months post-TAVI was 91%. Mortality rates were 18.5%, 12.9%, and 6.9% for patients with no statin, low-intensity or moderate-intensity statins, and high-intensity statins (P < 0.001). Any statin therapy proved to be effective in patients in different classes of age, risk, and manifest cardiovascular disease and was independent of background medication. Statins were of particular benefit in high-risk patients with coronary artery disease [hazard ratio (HR) = 0.57], ejection fraction <40% (HR = 0.64), or low-flow low-gradient aortic stenosis (HR = 0.58) and showed additional benefit even in patients taking renin–angiotensin system blockers (HR = 0.74). Statins also reduced mortality in patients with malignant disease (HR = 0.47). Our analysis confirmed the beneficial effect of statins on survival after TAVI and documented this phenomenon in key patient subsets. The protective effect of statins in our study is consistent with the cardioprotective mechanisms but must be explained by other, yet undetermined pleiotropic effects of statins.
Massage During Pregnancy and Postpartum
Authors: Pachtman Shetty Sarah L. , Fogarty Sarah
Published: July 2021

Massage is systematic touch and manipulation of the soft tissues of the body that is increasingly being used as an adjunctive therapy for stress relief and to promote relaxation and wellbeing during pregnancy and as an alternative to pharmacologic or invasive forms of analgesia during labor. Literature to support the use of massage in pregnancy and labor is limited; however, evidence to support its use has been increasing over the past 30 years. Massage has been shown to be valuable to pregnant women with anxiety, depression, leg, and back pain, and has shown significant benefit in perception of pain during labor.
Menopause: A Global Perspective and Clinical Guide for Practice
Authors: Voedisch Amy J. , Dunsmoor-Su Rebecca , Kasirsky Jennifer
Published: July 2021

Perimenopause and menopause are a time of great transition for women—physically, mentally, and emotionally. Symptoms of the menopause transition and beyond impact women worldwide. Unfortunately, physician knowledge and comfort with addressing menopausal concerns vary greatly, limiting the support physicians provide to women in need. This review aims to increase physician understanding of the epidemiology, physiology, symptomology, and treatment options available for perimenopausal and menopausal women. Our goal is to empower physicians to educate and treat their patients to reduce the negative impact of perimenopausal changes and enhance overall well-being for women.
Deep learning-based natural language processing in ophthalmology: applications, challenges and future directions
Authors: Yang Lily Wei Yun , Ng Wei Yan , Foo Li Lian , Liu Yong , Yan Ming , Lei Xiaofeng , Zhang Xiaoman , Ting Daniel Shu Wei
Published: July 2021

Purpose of review

Artificial intelligence (AI) is the fourth industrial revolution in mankind's history. Natural language processing (NLP) is a type of AI that transforms human language, to one that computers can interpret and process. NLP is still in the formative stages of development in healthcare, with promising applications and potential challenges in its applications. This review provides an overview of AI-based NLP, its applications in healthcare and ophthalmology, next-generation use case, as well as potential challenges in deployment.

Recent findings

The integration of AI-based NLP systems into existing clinical care shows considerable promise in disease screening, risk stratification, and treatment monitoring, amongst others. Stakeholder collaboration, greater public acceptance, and advancing technologies will continue to shape the NLP landscape in healthcare and ophthalmology.

Healthcare has always endeavored to be patient centric and personalized. For AI-based NLP systems to become an eventual reality in larger-scale applications, it is pertinent for key stakeholders to collaborate and address potential challenges in application. Ultimately, these would enable more equitable and generalizable use of NLP systems for the betterment of healthcare and society.
Defining Age-specific Relationships of Respiratory Syncytial Virus and Rhinovirus Species in Hospitalized Children With Acute Wheeze
Authors: Oo Stephen W.C. , Khoo Siew-Kim , Cox Des W. , Chidlow Glenys , Franks Kimberley , Prastanti Franciska , Bochkov Yury A. , Borland Meredith L. , Zhang Guicheng , Gern James E. , Smith David W. , Bizzintino Joelene A. , Laing Ingrid A. , Le Souëf Peter N.
Published: July 2021

Background:

Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined. Hence, this study aimed to establish these relationships in a large cohort of prospectively recruited hospitalized children.

Methods:

The study cohort was 390 children 0–16 years of age presenting with acute wheezing to a children’s emergency department, 96.4% being admitted. A nonwheezing control population of 190 was also recruited. Nasal samples were analyzed for viruses.

Results:

For the first 6 months of life, RSV was the dominant virus associated with wheezing (P < 0.001). From 6 months to 2 years, RSV, RV-A and RV-C were all common but none predominated. From 2 to 6 years, RV-C was the dominant virus detected (50–60% of cases), 2–3 times more common than RV-A and RSV, RSV decreasing to be absent from 4 to 7 years. RV-B was rare at all ages. RV-C was no longer dominant in children more than 10 years of age. Overall, RV-C was associated with lower mean oxygen saturation than any other virus (P < 0.001). Controls had no clear age distribution of viruses.

Conclusion:

This study establishes a clear profile of age specificity of virus infections causing moderate to severe wheezing in children: RSV as the dominant cause in the first 6 months and RV-C in preschool-age children.
Force of lifelong crystalline lens growth: chronic traumatic mechanical insult to the choroid
Authors: Strenk Lawrence M. , Guo Suqin , Lu Kenneth , Werner Liliana , Strenk Susan A.
Published: July 2021

Purpose:

To calculate the forces applied to the uvea and retina as a result of lifelong crystalline lens growth.

Design:

Retrospective study.

Setting:

MRI Research, Inc., Middleburg Heights, Ohio; Institute of Ophthalmology and Visual Science UMDNJ–New Jersey Medical School, Newark, New Jersey; USC Psychology University of Southern California, Los Angeles.

Methods:

Magnetic resonance images were acquired from 15 phakic/pseudophakic eye pairs in patients with cataract (ages 46 to 83 years). Choroidal lengths were measured. The forces required to produce differences between phakic/pseudophakic choroidal lengths were calculated.

Results:

The length of the choroid is greater in the phakic eye compared with the corresponding pseudophakic eye (n = 15), and this difference increases with age (P = .00006; power = 0.99). The corresponding choroidal strain also increases with age (P = .00003, power = 0.99) as do the forces required to produce such a change in choroidal length (P = .000008, power = 0.99).

Conclusions:

The authors theorize that lifelong crystalline lens growth applies a chronic, traumatic, mechanical insult to the uvea and retina. This previously unknown, ever-increasing, force appears to stretch the choroidal tissue and may be an intraocular pressure–independent modifiable risk factor for retinal disease. Implications exist for understanding the pathophysiology of retinal diseases in the aging eye that are often comorbid with cataracts, for example, glaucoma, macular degeneration, and diabetic retinopathy.
Preliminary Efficacy of an Emotion Regulation Intervention on Physical Activity and Depressive and Anxious Symptoms in Individuals in Cardiac Rehabilitation
Authors: Wierenga Kelly L. , Fresco David M. , Alder Megan , Sattar Abdus , Moore Shirley M.
Published: July 2021

Background

For the 720 000 Americans expected to experience a new acute cardiac event this year, cardiac rehabilitation is an important part of recovery. Symptoms of depression and anxiety undermine recovery efforts, leaving recovering patients at risk for diminished functional capacity and heightened risk of mortality. Poor emotion regulation can worsen symptoms of depression and anxiety and hinder recovery efforts.

Objective

The purpose of this randomized controlled trial was to evaluate the early efficacy testing of a theoretically based emotion regulation treatment (Regulating Emotions to Improve Self-management of Nutrition, Exercise, and Stress [RENEwS]) designed to assist survivors of an acute cardiac event in cardiac rehabilitation to optimize recovery.

Methods

Survivors of an acute cardiac event in cardiac rehabilitation (n = 30, 83% men) were randomized to five 1-hour in-person group sessions of RENEwS or a phone-based attention-control group. Participants completed measures of depression and anxiety symptoms at 3 time points. Moderate to vigorous physical activity (MVPA) was objectively measured for 7 days at each time point using waist-worn actigraphy monitors. Between-group differences were calculated using analysis of variance with Cohen f effect sizes calculated to evaluate initial efficacy.

Results

There was no statistically significant difference in depression, anxiety, or MVPA over time based on group assignment (all P > .05). Compared with attention control participants, in RENEwS participants, preliminary effects showed greater reductions in depression (Cohen f = 0.34) and anxiety (Cohen f = 0.40) symptoms but only modest improvements in MVPA from baseline to 5 months (Cohen f = 0.08).

Conclusions

Findings show that RENEwS is a promising emotion regulation intervention to enhance cardiac rehabilitation and potentially decrease symptoms of depression and anxiety.
First-in-man Implantation of a Cardiac Microcurrent Device for Chronic Systolic Heart Failure
Authors: Schmitto Jan D. , Napp L. Christian , Mariani Silvia , Hanke Jasmin S. , Li Tong , Vogel-Claussen Jens , Brandes Kersten , Göttel Peter , Müller Johannes , Dogan Guenes , Bauersachs Johann , Haverich Axel
Published: July 2021

Current therapies significantly improve survival and clinical endpoints in patients suffering from chronic heart failure with reduced ejection fraction (HFrEF), but most are not sufficient to reverse adverse remodeling and improve myocardial contractility. Herein, we report the first-in-man experience with a novel fully implantable device for cardiac electrical microcurrent (C-MIC) application. A 79-year-old man suffering from HFrEF (dilated cardiomyopathy, NYHA class III, left ventricular ejection fraction 30%) successfully underwent implantation of the C-MIC device through left anterolateral thoracotomy. At 30-day follow-up, no device-related complications were observed, demonstrating feasibility of C-MIC implantation in a patient suffering from HFrEF.
An Extracorporeal Membrane Oxygenation First Strategy in COVID-19 Acute Respiratory Distress Syndrome
Authors: Aziz Jenna E. , Dellavolpe Jeffrey , Aziz Salim , Sterling Rachel
Published: July 2021

COVID-19 can be associated with acute respiratory distress syndrome, which increases the likelihood of morbidity and mortality. Ventilator-induced lung injury is a known complication of mechanical ventilation (MV) and can further compound lung injury and recovery. Escalation to extracorporeal membrane oxygenation can be required in patients who deteriorate on MV. We report our experience with complete avoidance of MV using an ECMO First strategy deployed in an awake nonintubated COVID-19 patient with severe pneumonia.
Secondary pneumonias in critically ill patients with COVID-19: risk factors and outcomes
Authors: Povoa Pedro , Martin-Loeches Ignacio , Nseir Saad
Published: July 2021

Purpose of review

The aim of this review is to provide an overview of the current evidence of secondary pneumonias in COVID-19 patients, its incidence, risk factors and impact outcomes.

Recent findings

Early studies reported low incidence of hospital-acquired infections in COVID-19 patients. More recent large studies clearly showed that the incidence of secondary pneumonias was markedly high in patients under mechanical ventilation. Duration of mechanical ventilation, acute respiratory distress syndrome, prone position and male sex were identified as risk factors. The adjunctive therapy with steroids and immunomodulators were associated with a higher risk of pneumonia and invasive pulmonary Aspergillosis. Although secondary pneumonias seemed to be associated with poor outcomes, namely mortality, in comparison with influenza, no difference was found in heterogeneity of outcomes. Immunosuppressive therapy has been studied in several observational and randomized trials with conflicting results and the true impact on superinfections, namely secondary pneumonias, has not been properly assessed.

According to the current evidence, COVID-19 patients are at an increased risk of secondary pneumonias. The impact of immunosuppressive therapies on superinfections is yet to be determined. Further studies are needed to assess the true risk of secondary infections associated with immunosuppressive therapies and to identify preventive strategies.
The development of artificial livers
Authors: Misra Asish C. , Eckhoff Devin
Published: July 2021

Purpose of review

While liver transplantation is an established treatment for liver failure, the number of patients with liver failure amenable to such intervention far outnumbers the donor supply of livers. Technologies serving to bridge this gap are required. Artificial livers may serve as an alternative. In this review, we discuss the development of artificial liver technologies.

Recent findings

The accrued clinical data suggest that current liver assist devices may serve a role in specific liver diseases, but for the most part no survival benefit has been demonstrated. More clinical trials are expected to elucidate their utilization. Simultaneously, recent advances in materials and tissue engineering are allowing for exciting developments for novel artificial livers.

As there continues to be more clinical data regarding the use of current liver devices, new intricate artificial liver technologies, with the use of sophisticated three-dimensional materials, are being developed that may help improve outcomes of liver failure patients.
Obesity Increases the Risk of Hospital Readmission Following Intestinal Surgery for Children With Crohn Disease
Authors: Egberg Matthew D. , Galanko Joseph A. , Banegas Marcela , Roberson Mya , Strassle Paula D. , Phillips Michael , Kappelman Michael D.
Published: July 2021

Objectives:

Obese habitus can lead to adverse outcomes for colorectal surgeries due to technical challenges and pro‐inflammatory immune mediators associated with excess adipose tissue. Surgical planning, pre‐operative risk stratification, and patient counseling of pediatric Crohn disease (CD) patients are limited by the scarcity of data on this topic. We sought to determine the association between obesity and hospital readmission in children with CD undergoing intestinal resection.

Methods:

We used the National Surgical Quality Improvement Program‐Pediatric (NSQIP‐P) database to identify pediatric CD patients undergoing intestinal resection between 2012 and 2018. We calculated age‐ and sex‐adjusted body mass index (BMI) z scores using CDC population statistics. We used logistic regression to evaluate the association between obesity and readmission compared to average‐BMI patients adjusting for age, race, sex, steroid exposure, disease activity, and surgery type.

Results:

We evaluated 1258 pediatric CD intestinal resections occurring between 2012 and 2018. Patients were predominantly adolescent (91%), white (84%), and male (56%). Those with average BMI comprised 50% of the cohort, 31% were underweight, 11% overweight, and 8% obese. The overall 30‐day hospital readmission rate was 8.8%. Compared to those with average BMI, obese children had a 2‐fold (adjusted odds ratio 1.9, 95% confidence interval 1.0–3.8) increase in risk of hospital readmission.

Conclusions:

Obese patients undergoing intestinal resection face a higher risk of 30‐day hospital readmission compared to average‐BMI patients. These results can inform pre‐surgical risk counseling and underscore the need for long‐term weight management strategies to aid in risk reduction for obese children with CD at risk of future surgery.
Deep Herpes
Authors: Krystel-Whittemore Melissa , Chan May P. , Shalin Sara C. , Sauder Kenan J. , Hudson Amy , Foreman Ruth K. , Hoang Mai P. , Brennick Jeoffry B. , Yan Shaofeng , Nazarian Rosalynn M.
Published: July 2021

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.
Wnt Family Member 9b (Wnt9b) Is a New Sensitive and Specific Marker for Breast Cancer
Authors: Lu Shaolei , Yakirevich Evgeny , Yang Dongfang , Xiao Ying , Wang Li Juan , Wang Yihong
Published: July 2021

Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor’s breast origin. However, their specificities still have room to improve. Many nonbreast tumors express cytokeratin 7 and estrogen receptor, and urothelial tumors frequently express GATA3. There is a practical need for a new breast lineage marker that is sensitive and specific. Wnt family member proteins play critical roles in embryo development, tissue homeostasis and tumor development through β-catenin dependent and independent pathways. The current study evaluated Wnt9b and GATA3 expression in 163 primary breast cancers, 63 metastatic breast cancers, and 525 nonbreast epithelial tumors. The positive rates of Wnt9b and GATA3 in primary breast cancer were both 98.7%. The positive rates in metastatic breast cancer were 87.3% for Wnt9b and 96.8% for GATA3. For nonbreast tumors, including 64 cases of urothelial carcinoma, Wnt9b was negative in all except salivary gland carcinomas. The study demonstrated that Wnt9b is a breast cancer marker with similar sensitivity as GATA3 but with greater specificity than GATA3 and may ultimately become a useful diagnostic tool in routine surgical pathology practice.
Progress Toward the 90-90-90 HIV Targets in Zimbabwe and Identifying Those Left Behind
Authors: Hakim Avi J. , Tippett Barr Beth A. , Kinchen Steven , Musuka Godfrey , Manjengwa Julius , Munyati Shungu , Gwanzura Lovemore , Mugurungi Owen , Ncube Getrude , Saito Suzue , Parekh Bharat S. , Patel Hetal , Duong Yen T. , Gonese Elizabeth , Sleeman Katrina , Ruangtragool Leala , Justman Jessica , Herman-Roloff Amy , Radin Elizabeth
Published: July 2021

Objective:

We present findings from the nationally representative Zimbabwe Population–based HIV Impact Assessment that characterize Zimbabwe's progress toward the Joint United Nations Programme on HIV/AIDS 90-90-90 targets.

Design:

We conducted a cross-sectional household survey.

Methods:

Consenting adults and children in the household were eligible to participate in Zimbabwe Population–based HIV Impact Assessment (October 2015–August 2016). Participants completed face-to-face interviews and provided blood for HIV, CD4, viral load, and syphilis testing. Viral load suppression (VLS) was defined as HIV RNA <1000 copies/mL. HIV-positive specimens were tested for the presence of selected antiretroviral drugs. Data were weighted. Analysis was restricted to HIV-positive adults aged 15–64 years.

Results:

We enrolled 11,098 men and 14,033 women aged 15–64 years. HIV prevalence was 14.1%. Of those living with HIV, 76.8% (95% confidence interval [CI]: 74.9 to 78.7) were aware of their HIV status or had detectable antiretroviral levels. Of these, 88.4% (95% CI: 87.1 to 89.7) were receiving antiretroviral therapy (ART), and of these people, 85.3% (95% CI: 83.4 to 87.1) had VLS. Male sex age 15–34 years and having 1 or more sexual partners were associated with being unaware of one's HIV-positive status. Age <50 years and not taking cotrimoxazole were associated with being less likely to be being both aware and taking ART. Male sex, age <50 years, and taking cotrimoxazole were associated with being on ART but not having VLS.

Conclusions:

Zimbabwe has made great strides toward epidemic control. Focusing resources on case finding, particularly among men, people aged <35 years, and sexually active individuals can help Zimbabwe attain 90-90-90 targets.
Clinical Significance of Raynaud Phenomenon in Systemic Lupus Erythematosus
Authors: Barbacki Ariane , Rached-d'Astous Nour , Pineau Christian A. , Vinet Evelyne , Grenier Louis-Pierre , Kalache Fares , Fallavollita Sabrina , Lukusa Luck , Bernatsky Sasha
Published: July 2021

Objective

There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort.

Methods

We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011–2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE.

Results

Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07–6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10–3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10–3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73–5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated.

Conclusions/Discussion

Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.
Mariniflexile maritimum sp. nov., isolated from seawater of the South Sea in the Republic of Korea
Authors: Ko So-Ra , Le Ve Van , Jin Long , Lee Sang-Ah , Ahn Chi-Yong , Oh Hee-Mock
Published: July 2021

A novel Gram-stain-negative, rod-shaped, aerobic, non-motile bacterial strain, designated M5A1MT, was isolated from seawater collected from the South Sea of the Republic of Korea. Based on 16S rRNA gene sequence similarity, strain M5A1MT was closely related to

Mariniflexile gromovii

KMM 6038T (95.3 %),

Mariniflexile fucanivorans

SW5T (95.2 %),

Mariniflexile soesokkakense

RSSK-9T (95.1 %),

Yeosuana aromativorans

GW1-1T (94.6 %) and

Confluentibacter lentus

HJM-3T (94.6 %). Genome-based phylogenetic analyses revealed that strain M5A1MT formed a distinct cluster with the type strains of the genus

Mariniflexile

. The major cellular fatty acid constituents (>5 % of the total fatty acids) were iso-C15:0, anteiso-C15 : 0, iso-C15 : 0 3-OH, iso-C15 : 1 G, iso-C16:03-OH and iso-C17 : 0 3-OH. The respiratory quinone was identified as MK-6. The major polar lipids were phosphatidylethanolamine and one unidentified polar lipid. The genomic DNA G+C content of strain M5A1MT was determined to be 37.7 mol%. On the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics, strain M5A1MT is considered to represent a novel species within the genus

Mariniflexile

, for which the name Mariniflexile maritimum sp. nov. is proposed. The type strain is M5A1MT (=KCTC 72895T=JCM 33982T).
Whole-genome sequencing analysis of clozapine-induced myocarditis
Authors: Narang Ankita , Lacaze Paul , Ronaldson Kathlyn J , McNeil John J , Jayaram Mahesh , Thomas Naveen , Sellmer Rory , Crockford David , Stowe Robert , Greenway Steven C. , Pantelis Christos , Bousman Chad A
Published: July 2021

One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN)nominally associated (p<0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Major sex differences in migraine prevalence among occupational categories: a cross-sectional study using UK Biobank
Authors: Affatato Oreste , Miguet Maud , Schiöth Helgi B. , Mwinyi Jessica
Published: July 2021

Migraine represents one of the most prevalent neurological conditions worldwide. It is a disabling condition with high impact on the working situation of migraineurs. Interestingly, gender-related differences regarding an association of migraine with important occupational characteristics has been hardly studied. The current study scrutinizes gender-specific differences in the prevalence of migraine across a broad spectrum of occupational categories, shedding also light on associations with important job-related features such as shift work, job satisfaction, and physical activity. The study included data from 415 712 participants from the UK Biobank cohort, using the official ICD10 diagnosis of migraine and other health conditions as selection criteria. Prevalence ratios of migraineurs compared to healthy controls among different occupational categories and job-related variables were estimated using log-binomial regression analyses. Statistical models were adjusted for important sociodemographic features such as age, BMI, ethnicity, education and neuroticism. To better highlight specific differences between men and women we stratified by sex. We detected a differential prevalence pattern in relation to different job categories between men and women. Especially in men, migraine appears to be more prevalent in highly physically demanding occupations (PR 1.38, 95% CI [0.93, 2.04]). Furthermore, migraine is also more prevalent in jobs that frequently involve shift or night shift work compared to healthy controls. Interestingly, this prevalence is especially high in women (shift work PR 1.45, 95% CI [1.14, 1.83], night shift work PR 1.46, 95% CI [0.93, 2.31]). Our results show that higher migraine prevalence is associated with physically demanding jobs and shift working.
Outbreak of P.3 (Theta) SARS-CoV-2 emerging variant of concern among service workers in Louisiana
Authors: Rose Rebecca , Nolan David J. , LaFleur Tessa M. , Lamers Susanna L.
Published: July 2021

In May, 2021, during routine oil and gas industrial quarantine/premobilization procedures, four individuals who recently arrived to Louisiana from the Philippines tested positive for SARS-CoV-2. Subsequent genomic analysis showed that all were infected with a Variant of Interest (P.3-Theta). This increases the number of known P.3 infections in the United States to eleven and highlights the importance of genomic surveillance within industries that are prone to rapidly spread the infection.
Photoacoustic-MR Image Registration Based on a Co-Sparse Analysis Model to Compensate for Brain Shift
Authors: Farnia Parastoo , Makkiabadi Bahador , Alimohamadi Maysam , Najafzadeh Ebrahim , Basij Maryam , Yan Yan , Mehrmohammadi Mohammad , Ahmadian Alireza
Published: July 2021

Brain shift is an important obstacle to the application of image guidance during neurosurgical interventions. There has been a growing interest in intra-operative imaging to update the image-guided surgery systems. However, due to the innate limitations of the current imaging modalities, accurate brain shift compensation continues to be a challenging task. In this study, the application of intra-operative photoacoustic imaging and registration of the intra-operative photoacoustic with pre-operative MR images is proposed to compensate for brain deformation. Finding a satisfactory registration method is challenging due to the unpredictable nature of brain deformation. In this study, the co-sparse analysis model is proposed for photoacoustic -MR image registration, which can capture the interdependency of the two modalities. The proposed algorithm works based on the minimization of the mapping transform via a pair of analysis operators that are learned by the alternating direction method of multipliers. The method was evaluated using experimental phantom and ex-vivo data obtained from the mouse brain. The results of phantom data show about 63% improvement in target registration error in comparison with the commonly used normalized mutual information method. Results proved that intra-operative photoacoustic images could become a promising tool when the brain shift invalidated pre-operative MRI.
The human nose organoid respiratory virus model: an ex-vivo human challenge model to study RSV and SARS-CoV-2 pathogenesis and evaluate therapeutics
Authors: Rajan Anubama , Weaver Ashley Morgan , Aloisio Gina Marie , Jelinski Joseph , Johnson Hannah L. , Venable Susan F. , McBride Trevor , Aideyan Letisha , Piedra Felipe-Andrés , Ye Xunyan , Melicoff-Portillo Ernestina , Yerramilli Malli Rama Kanthi , Zeng Xi-Lei , Mancini Michael A , Stossi Fabio , Maresso Anthony W. , Kotkar Shalaka A. , Estes Mary K. , Blutt Sarah , Avadhanula Vasanthi , Piedra Pedro A.
Published: July 2021

There is an unmet need for pre-clinical models to understand the pathogenesis of human respiratory viruses; and predict responsiveness to immunotherapies. Airway organoids can serve as an ex-vivo human airway model to study respiratory viral pathogenesis; however, they rely on invasive techniques to obtain patient samples. Here, we report a non-invasive technique to generate human nose organoids (HNOs) as an alternate to biopsy derived organoids. We made air liquid interface (ALI) cultures from HNOs and assessed infection with two major human respiratory viruses, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Infected HNO-ALI cultures recapitulate aspects of RSV and SARS-CoV-2 infection, including viral shedding, ciliary damage, innate immune responses, and mucus hyper-secretion. Next, we evaluated the feasibility of the HNO-ALI respiratory virus model system to test the efficacy of palivizumab to prevent RSV infection. Palivizumab was administered in the basolateral compartment (circulation) while viral infection occurred in the apical ciliated cells (airways), simulating the events in infants. In our model, palivizumab effectively prevented RSV infection in a concentration dependent manner. Thus, the HNO-ALI model can serve as an alternate to lung organoids to study respiratory viruses and testing therapeutics.
Chemogenetic Inhibition of Corticostriatal Circuits Reduces Cued Reinstatement of Methamphetamine Seeking
Authors: Kearns Angela M. , Siemsen Benjamin M. , Hopkins Jordan L. , Weber Rachel A. , Scofield Michael D. , Peters Jamie , Reichel Carmela M.
Published: July 2021

Methamphetamine (meth) causes enduring changes within the medial prefrontal cortex (mPFC) and the nucleus accumbens (NA). Projections from the mPFC to the NA have a distinct dorsal-ventral distribution, with the prelimbic (PL) mPFC projecting to the NAcore, and the infralimbic (IL) mPFC projecting to the NAshell. Inhibition of these circuits has opposing effects on cocaine relapse. Inhibition of PL-NAcore reduces cued reinstatement of cocaine seeking and IL-NAshell inhibition reinstates cocaine seeking. Meth, however, exhibits a different profile, as pharmacological inhibition of either the PL or IL decrease cued reinstatement of meth-seeking. The potentially opposing roles of the PL-NAcore and IL-NAshell projections remain to be explored in the context of cued meth seeking. Here we used an intersectional viral vector approach that employs a retrograde delivery of Cre from the NA and Cre-dependent expression of DREADD in the mPFC, in both male and female rats to inhibit or activate these parallel pathways. Inhibition of the PL-NAcore circuit reduced cued reinstatement of meth seeking under short and long-access meth self-administration and after withdrawal with and without extinction. Inhibition of the IL-NAshell also decreased meth cued reinstatement. Activation of the parallel circuits was without an effect. These studies show that inhibition of the PL-NAcore or the IL-NAshell circuits can inhibit reinstated meth seeking. Thus, the neural circuitry mediating cued reinstatement of meth seeking is similar to cocaine in the dorsal, but not ventral, mPFC-NA circuit.
Comparative analysis of single nucleotide polymorphisms and microsatellite markers for parentage verification and discovery within the equine Thoroughbred breed
Authors: Flynn P. , Morrin-O’Donnell R. , Weld R. , Gargan L. M. , Carlsson J. , Daly S. , Suren H. , Siddavatam P. , Gujjula K. R.
Published: July 2021

Short tandem repeat (STR), also known as microsatellite markers are currently used for genetic parentage verification within equine. Transitioning from STR to single nucleotide polymorphism (SNP) markers to perform equine parentage verification is now a potentially feasible prospect and a key area requiring evaluation is parentage testing accuracies when using SNP based methods, in comparison to STRs. To investigate, we utilised a targeted equine genotyping by sequencing (GBS) panel of 562 SNPs to SNP genotype 309 Thoroughbred horses - inclusive of 55 previously parentage verified offspring. Availability of STR profiles for all 309 horses, enabled comparison of parentage accuracies between SNP and STR panels. An average sample call rate of 97.2% was initially observed, and subsequent removal of underperforming SNPs realised a pruned final panel of 516 SNPs. Simulated trio and partial parentage scenarios were tested across 12-STR, 16-STR, 147-SNP and 516-SNP panels. False-positives (i.e. expected to fail parentage, but pass) ranged from 0% for 147-SNP and 516-SNP panels to 0.003% when using 12-STRs within trio parentage scenarios, and 0% for 516-SNPs to 1.6% for 12-STRs within partial parentage scenarios. Our study leverages targeted GBS methods to generate low-density equine SNP profiles and demonstrates the value of SNP based equine parentage analysis in comparison to STRs - particularly when performing partial parentage discovery.