bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking the Presence of Macular Oedema to Structural and Functional Alterations in Retinitis Pigmentosa
Authors: Friesacher Anna , Lopez Torres Lisette T. , Valmaggia Christophe , Rüesch Reinhard , Todorova Margarita G.
Published: April 2021

Objective To investigate the association between the central retinal thickness (CRT), the retinal nerve fibre layer thickness (RNFL), and the functional alterations in retinitis pigmentosa (RP) patients.

Methods Forty-three patients with typical RP and nineteen age-matched controls, who underwent SD-OCT (macular and optic disc OCT protocols) and electrophysiology, were included. The RP group was divided into two subgroups: with clinical appearance of macular oedema (ME-RP; 30 eyes) and without macular oedema (no-ME; 44 eyes). Central retinal thickness OCT data were averaged in three zones (zone 1 [0°–3°], zone 2 [3°–8°], and zone 3 [8°–15°]) and were evaluated in relation to the RNFL thickness and electrophysiological data.

Results The ME-RP group showed increased CRT (zone 1) and RNFL thickness compared to the controls and no-ME-RP (p ≤ 0.002). The no-ME-RP group had reduced CRT thickness (all zones; p ≤ 0.018) compared to the controls and ME-RP, whereas the RNFL thickness in the no-ME-RP group was reduced only compared to the ME-RP group (p < 0.001). The ME-RP group showed significantly more attenuated functional responses than the no-ME-RP patients. A significant positive interaction was found between the CRT (zones 1 and 2) and the RNFL thickness within ME-RP (p ≤ 0.010). Significant negative interactions were found between CRT, RNFL thickness, and functional findings within ME-RP (p ≤ 0.049).

Conclusion The presence of macular oedema correlated well with increased RNFL thickness and residual function in RP patients. Such association provides evidence of an underlying transneuronal mechanism of retinal degeneration. Simultaneous monitoring of CRT and RNFL thickness may help in the future to evaluate the progression of the disease and the efficacy of treatments in RP patients.
A Withanolide-rich Fraction of Athenaea velutina Induces Apoptosis and Cell Cycle Arrest in Melanoma B16F10 Cells
Authors: Almeida Alisson A. , Lima Graziela D. A. , Eiterer Marinês , Rodrigues Laís A. , A. do Vale Juliana A. , Zanatta Ana C. , Bressan Gustavo C. , de Oliveira Leandro L. , Leite João P. V.
Published: April 2021

Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed
FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.
„Es spielt keine Rolle, ob der Nudelauflauf am Ende versalzen ist“ – Fachlehrkräfte für Sonderpädagogik
Authors: Laquai Sophia
Published: April 2021

Eine Körperbehinderung im Sinne eines biopsychosozialen Verständnisses hat häufig unmittelbare Auswirkungen auf alle Lern- und Entwicklungsbereiche von Kindern und Jugendlichen. Physios können in Baden-Württemberg als Fachlehrkräfte dazu beitragen, dass Funktionseinschränkungen sowie Bewegungsbarrieren zu einer möglichst geringen Bildungseinschränkung führen.
Ungeahnte Kräfte – Sport- und Bewegungstherapie bei onkologischen Erkrankungen
Authors: Voland Annelie , Köppel Maximilian , Wiskemann Joachim
Published: April 2021

Inzwischen belegen mehr als 700 Studien die positive Wirkung körperlicher Aktivität vor, während und nach der Krebstherapie. Trotzdem sind Physios in der Therapie oft zögerlich, aus Angst, etwas falsch zu machen. Warum aber gerade Nichtstun verheerend sein kann und wie ein sicheres Training gelingt, beleuchtet dieser Artikel.
Hygiene bei der HNO-Untersuchung: Fluoreszenzstudie mit Übersicht der aktuellen Empfehlungen
Authors: Rohrmeier Christian , Schneider-Brachert Wulf , Kühnel Thomas , Hitzenbichler Florian , Holzmann Thomas , Bohr Christopher
Published: April 2021

Steigende normative Ansprüche an Patientensicherheit und Maßnahmen der Qualitätssicherung, aber auch die Problematik multiresistenter Keime und von Erregern mit hohem Ansteckungspotenzial, verstärken die Notwendigkeit hygienisch korrekten Arbeitens.

In dieser Studie sollten hygienisch relevante potenzielle Kontaminationsquellen bei
der HNO-Untersuchung identifiziert und mögliche Verbesserungsstrategien untersucht
werden.

Von 5 Untersuchern mit unterschiedlicher Berufserfahrung, deren Handschuhe vor der
Untersuchung mit Fluoreszenzlotion benetzt wurden, wurde eine komplette HNO-Untersuchung
durchgeführt. Kontaminierungen insbesondere an der Untersuchungseinheit und am
Instrumentarium wurden identifiziert. Das potenzielle Risiko einer Übertragung von
Erregern auf Folgepatienten wurde mittels eines eigens entwickelten Scores bewertet.
Verschiedene Strategien zur Reduzierung identifizierter Kontaminationsmöglichkeiten
wurden erarbeitet und gedanklich durchgespielt.

Der Score der Untersucher war mit im Mittel 87,4 Punkten (±3,6) sehr hoch. Die
Umsetzung von einzelnen Hygienemaßnahmen im Untersuchungsablauf würde zu einer
deutlichen Erniedrigung des Scores und damit einer Verbesserung der Hygiene führen: kein
Händeschütteln (81,8), zusätzlich Patientenstuhldesinfektion (79,8), Desinfektion
wichtiger Flächen (69,8), Bereitstellen von Standardinstrumenten (60,2) oder aller
Instrumente (32,2), Desinfektion aller relevanten Flächen und Bereitstellen aller
Instrumente (7,4).

Die Ergebnisse zeigen sehr deutlich, dass eine HNO-Untersuchung aus Sicht der Hygiene
einen komplexen Vorgang darstellt. Für einen verlässlichen Schutz vor möglichen
Übertragungsereignissen ist deshalb eine strukturierte Bündelung von Hygienemaßnahmen
notwendig.
Advances in Transition-Metal-Catalyzed C–H Bond Oxygenation of Amides
Authors: Punji Benudhar , Vijaykumar Muniyappa
Published: April 2021

C–O bond formation represents a fundamental chemical transformation in organic synthesis to develop valuably oxygenated (hetero)arenes. Particularly, the direct and regioselective C–H bond oxygenation of privileged amides, using a transition metal catalyst and a mild oxygenating source, is a step-economy and attractive approach. During the last decade, considerable progress has been realized in the direct C–H oxygenation of primary, secondary, and tertiary amides. This Short Review compiles the advances in transition-metal-catalyzed oxygenation of C(sp2)–H and C(sp3)–H bonds on various amides with diverse oxygenation sources. The review is categorized into two different major sections: (i) C(sp2)–H oxygenation and (ii) C(sp3)–H oxygenation. Each section is discussed based on the directing group (monodentate and bidentate) attached to the amide derivatives.

1 Introduction

2 C(sp2)–H Oxygenation

2.1 Monodentate Directed

2.2 Bidentate Directed

3 C(sp3)–H Oxygenation

3.1 Monodentate Directed

3.2 Bidentate Directed

4 Conclusion and Outlook
Role of Membrane Lipid Rafts in MRP4 (ABCC4) Dependent Regulation of the cAMP Pathway in Blood Platelets
Authors: Belleville-Rolland Tiphaine , Leuci Alexandre , Mansour Alexandre , Decouture Benoit , Martin Fanny , Poirault-Chassac Sonia , Rouaud Margot , Guerineau Hippolyte , Dizier Blandine , Pidard Dominique , Gaussem Pascale , Bachelot-Loza Christilla
Published: April 2021

Background Platelet cytosolic cyclic adenosine monophosphate (cAMP) levels are balanced by synthesis, degradation, and efflux. Efflux can occur via multidrug resistant protein-4 (MRP4; ABCC4) present on dense granule and/or plasma membranes. As lipid rafts have been shown to interfere on cAMP homeostasis, we evaluated the relationships between the distribution and activity of MRP4 in lipid rafts and cAMP efflux.

Methods Platelet activation and cAMP homeostasis were analyzed in human and wild-type or MRP4-deleted mouse platelets in the presence of methyl-β-cyclodextrin (MßCD) to disrupt lipid rafts, and of activators of the cAMP signalling pathways. Human platelet MRP4 and effector proteins of the cAMP pathway were analyzed by immunoblots in lipid rafts isolated by differential centrifugation.

Results MßCD dose dependently inhibited human and mouse platelet aggregation without affecting per se cAMP levels. An additive inhibitory effect existed between the adenylate cyclase (AC) activator forskolin and MßCD that was accompanied by an overincrease of cAMP, and which was significantly enhanced upon MRP4 deletion. Finally, an efflux of cAMP out of resting platelets incubated with prostaglandin E1 (PGE1) was observed that was partly dependent on MRP4. Lipid rafts contained a small fraction (≈15%) of MRP4 and most of the inhibitory G-protein Gi, whereas Gs protein, AC3, and phosphodiesterases PDE2 and PDE3A were all present as only trace amounts.

Conclusion Our results are in favour of part of MRP4 present at the platelet surface, including in lipid rafts. Lipid raft integrity is necessary for cAMP signalling regulation, although MRP4 and most players of cAMP homeostasis are essentially located outside rafts.
Acquired FXIII Deficiency is Associated with High Morbidity
Authors: Duque Patricia , Chasco-Ganuza Maite , Ortuzar Ariana , Almaraz Carolina , Terradillos Estrella , Perez-Rus Gloria , Pascual Cristina
Published: April 2021

Background A factor XIII (FXIII) level >30% is considered necessary to prevent spontaneous bleeding. Bleeding is also a risk in patients with acquired FXIII deficiency, but the hemostatic level of FXIII in this context remains to be determined.

Methods We retrospectively analyzed all patients diagnosed with acquired FXIII deficiency at a large hospital over 3 years (study ID NCT04416594, http://www.clinicaltrials.gov) and assessed clinical data to identify the best cut-off point for FXIII activity to distinguish between low and high risk of major bleeding in a mixed medical and surgical population.

Results Of the 97 patients who experienced bleeding despite a normal coagulation test, 43.2% had FXIII activity <70%. FXIII activity was significantly lower in surgical patients and patients admitted to the intensive care unit (ICU). Low FXIII activity was significantly associated with long ICU stays and a high incidence of major bleeding.

Conclusion Acquired FXIII deficiency is associated with high morbidity. The hemostatic level of FXIII in the setting of acquired FXIII deficiency might be above 30%.
Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors
Authors: von Hundelshausen Philipp , Lorenz Reinhard , Siess Wolfgang , Weber Christian
Published: April 2021

A series of cases with rare thromboembolic incidents including cerebral sinus vein thrombosis (some of them fatal) and concomitant thrombocytopenia occurring shortly after vaccination with the coronavirus disease 2019 (COVID-19) vaccine AZD1222 (Vaxzevria) have caused significant concern and led to its temporary suspension in many countries. Immediate laboratory efforts in four of these patients have identified a tentative pathomechanism underlying this syndrome termed initially vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) and renamed recently vaccine-induced immune thrombotic thrombocytopenia (VITT). It encompasses the presence of platelet-activating antibodies to platelet factor-4/heparin complexes, possibly emulated by polyanionic constituents of AZD1222, and thus resembles heparin-induced thrombocytopenia (HIT). Because these immune complexes bind and activate platelets via Fcγ receptor IIA (FcγRIIA), high-dose intravenous immunoglobulin G has been suggested for treatment of VITT in addition to non-heparin anticoagulants. Here we propose inhibitors of Bruton tyrosine kinase (Btk) approved for B cell malignancies (e.g., ibrutinib) as another therapeutic option in VITT, as they are expected to pleiotropically target multiple pathways downstream of FcγRIIA-mediated Btk activation, for example, as demonstrated for the effective inhibition of platelet aggregation, dense granule secretion, P-selectin expression and platelet-neutrophil aggregate formation stimulated by FcγRIIA cross-linking. Moreover, C-type lectin-like receptor CLEC-2- and GPIb-mediated platelet activation, the interactions and activation of monocytes and the release of neutrophil extracellular traps, as encountered in HIT, could be attenuated by Btk inhibitors. As a paradigm for emergency repurposing of approved drugs in COVID-19, off-label use of Btk inhibitors in a low-dose range not affecting haemostatic functions could thus be considered a sufficiently safe option to treat VITT.
Pyrimidine-Substituted Hexaarylbenzenes as Versatile Building Blocks for N–Doped Organic Materials
Authors: Meitinger Nicolas , Mengele Alexander K. , Nauroozi Djawed , Rau Sven
Published: April 2021

Hexaarylbenzenes (HABs) are valuable precursors for the bottom-up synthesis of (nano-)graphene structures. In this work the synthesis of several bis-pyrimidine substituted HABs furnished with tert-butyl groups at different sites of the four pendant phenyl rings is reported. The synthetic procedure is based on modular [4 + 2]-Diels–Alder cycloaddition reactions followed by decarbonylation. Analysis of the solid-state structures revealed that the newly synthesized HABs feature a propeller-like arrangement of the six arylic substituents around the benzene core. Here, the tilt of the aryl rings with respect to the central ring strongly depends on the intermolecular interactions between the HABs and co-crystallized solvent molecules. Interestingly, by evading the closest proximity of the central ring using an alkyne spacer, the distant pyrimidine ring is oriented in the coplanar geometry with regard to the benzene core, giving rise to a completely different UV-absorption profile.
Incidence of Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury in a Tertiary Care ICU: A Retrospective Cohort Study
Authors: Bhardwaj Ajit , Satapathy Ganesh C. , Garg Arpit , Chawla Vikas , Jangra Kiran
Published: April 2021

Background Paroxysmal sympathetic hyperactivity (PSH) is an understudied complication of traumatic brain injury (TBI). PSH usually presents with transient rise in sympathetic outflow, leading to increased blood pressure, heart rate, temperature, respiratory rate, sweating, and posturing activity. We retrospectively analyzed the incidence of PSH in TBI using PSH-assessment measure (PSH-AM) scale.

Methods This single-center retrospective cohort study was conducted in traumatic head injury patients admitted in the intensive care unit from January 1, 2016 to December 31, 2019 in a tertiary care center. The data was collected from the hospital database after obtaining approval from the hospital ethics committee.

Results A total of 287 patients (18–65 years of age) were admitted to intensive care unit (ICU) with TBI out of which 227 patients were analyzed who had ICU stay for more than 14 days. PSH was diagnosed in 70 (30.8%) patients. Mean age of PSH positive patients was 40 ± 18 and 49 ± 11 years for PSH negative patients (p < 0.001). The age group between 40 and 50 years had a higher incidence of PSH. The age and Glasgow coma score (GCS) were significantly associated with the occurrence of PSH. The GCS score demonstrated good accuracy for predicting the occurrence of PSH with AUC 0.83, 95% CI of 0.775 to 0.886, and a p-value of 0.001.

Conclusion We observed that the incidence of PSH was 30.8% in the patients with TBI. Age and GCS were found to have a significant association for predicting the occurrence of PSH. The patients who developed PSH had a longer length of hospital stay in ICU.
Homozygous UBA5 Variant Leads to Hypomyelination with Thalamic Involvement and Axonal Neuropathy
Authors: Al-Saady Murtadha L. , Kaiser Charlotte S. , Wakasuqui Felipe , Korenke G. Christoph , Waisfisz Quinten , Polstra Abeltje , Pouwels Petra J. W. , Bugiani Marianna , van der Knaap Marjo S. , Lunsing Roelineke J. , Liebau Eva , Wolf Nicole I.
Published: April 2021

The enzyme ubiquitin-like modifier activating enzyme 5 (UBA5) plays an important role in activating ubiquitin-fold modifier 1 (UFM1) and its associated cascade. UFM1 is widely expressed and known to facilitate the post-translational modification of proteins. Variants in UBA5 and UFM1 are involved in neurodevelopmental disorders with early-onset epileptic encephalopathy as a frequently seen disease manifestation. Using whole exome sequencing, we detected a homozygous UBA5 variant (c.895C > T p. [Pro299Ser]) in a patient with severe global developmental delay and epilepsy, the latter from the age of 4 years. Magnetic resonance imaging showed hypomyelination with atrophy and T2 hyperintensity of the thalamus. Histology of the sural nerve showed axonal neuropathy with decreased myelin. Functional analyses confirmed the effect of the Pro299Ser variant on UBA5 protein function, showing 58% residual protein activity. Our findings indicate that the epilepsy currently associated with UBA5 variants may present later in life than previously thought, and that radiological signs include hypomyelination and thalamic involvement. The data also reinforce recently reported associations between UBA5 variants and peripheral neuropathy.
Complications and Neurological Outcome following Intraoperative Aneurysm Rupture in Adult Patients Undergoing Intracranial Aneurysmal Clipping: A Retrospective Study
Authors: Radhakrishna Nayani , Khandelwal Ankur , Chouhan Rajendra Singh , Pandia Mihir Prakash , Burman Sourav , Mahapatra Rashmi Rani
Published: April 2021

Background Intraoperative aneurysmal rupture (IAR) is a catastrophic complication; however, its impact on neurological outcome is debatable. We studied the effects of IAR on intraoperative and postoperative complications and neurological outcome.

Methods In this retrospective study, adult patients who underwent aneurysmal clipping over a period of 2 years were divided as follows: group R (with IAR) and group N (without IAR). Various perioperative parameters, intraoperative and postoperative complications were noted. Glasgow outcome scale (GOS) was noted at discharge from hospital and categorized as favorable (GOS IV and V) and unfavorable (GOS I, II and III). Collected data was statistically analyzed. Univariate and multiple logistic regression analyses were performed to identify predictors of IAR. A p value < 0.05 was considered significant.

Results Thirty-two out of 195 (16.41%) patients suffered IAR, with majority involving anterior communicating artery aneurysm (46.88%). Duration of temporary clipping (p < 0.001), volume of blood loss, and fluid and blood transfusion were significantly more in group R. Postoperatively, significantly more patients in group R developed intracranial hematoma, cerebral infarct, and required prolonged ventilatory support (≥5 days). Unfavorable neurological outcome was observed more in group R (p = 0.013). In univariate analysis, blood loss > 500 mL, use of colloids, and duration of surgery > 5 hours were found to be associated with IAR. After multiple logistic regression analysis, only use of colloids and duration of surgery > 5 hours were the most predictive variables for IAR.

Conclusions IAR is associated with serious intraoperative and postoperative complications and unfavorable neurological outcome.
Diagnostic Validity of Orthopantomogram Compared to Dual Energy X-ray Absorptiometry Scan in Detecting Osteoporosis
Authors: Kumar D. Prasanna , Jayachandran S. , Thilagavathy N.
Published: April 2021

Introduction

Osteoporosis is one of the most common and rampant metabolic bone disorders among the geriatric, particularly affecting postmenopausal women. Even though resorption tends to occur more rapidly in bones with a higher proportion of trabecular bone (e.g., vertebrae, pelvis, calcaneus), bones with significant cortical bone content also do undergo resorption, for example, mandible. The dental manifestations that may indicate low-bone density include loose teeth, receding gums, and ill-fitting or loose dentures.

Objective

To validate the efficacy of orthopantomograms (OPGs) in recognizing bone mineral density (BMD) changes of the mandible using mandibular cortical index (MCI) and substantiate the same with dual energy X-ray absorptiometry (DEXA) scan on femoral neck and spine.

Materials and Methods

This cross-sectional study comprised 60 geriatric patients of both genders. All the patients were subjected to panoramic radiographs wherever clinically indicated. The visual analysis was done based on the radiographic appearance of the mandibular cortical border and results were compared with DEXA scan reports, followed by an analysis of three grades of MCI and BMD statistically.

Results

In our study, out of 40 patients in C2 and C3 subgroups, 67% and 20% were normal, respectively. The incidence of osteopenia was 33% in the C2 group and 70% in the C3 group, whereas Osteoporosis was present only among 10% of the population in the C3 group. The difference between the groups are statistically significant (p = 0.01). These findings imply that a progressive link exists between BMD and deteriorating cortical morphology.

Conclusion

The purpose of this study is that dentists will be able to refer patients to physicians of suspected low BMD, based on incidental findings on panoramic radiographs for further examination. There is a statistically significant correlation present between DEXA and MCI, so the latter can also be used for screening BMD changes.
Total Wrist Arthroplasty Alignment and Its Potential Association with Clinical Outcomes
Authors: Akhbari Bardiya , Shah Kalpit N. , Morton Amy M. , Molino Janine , Moore Douglas C. , Wolfe Scott W. , Weiss Arnold-Peter C. , Crisco Joseph J.
Published: April 2021

Purpose There is a lack of quantitative research that describes the alignment and, more importantly, the effects of malalignment on total wrist arthroplasty (TWA). The main goal of this pilot study was to assess the alignment of TWA components in radiographic images and compare them with measures computed by three-dimensional analysis. Using these measures, we then determined if malalignment is associated with range of motion (ROM) or clinical outcomes (PRWHE, PROMIS, QuickDash, and grip strength).

Methods Six osteoarthritic patients with a single type of TWA were recruited. Radiographic images, computed tomography images, and clinical outcomes of the wrists were recorded. Using posteroanterior and lateral radiographs, alignment measurements were defined for the radial and carpal components. Radiographic measurements were validated with models reconstructed from computed tomography images using Bland–Altman analysis. Biplanar videoradiography (<1mm and <1 degree accuracy) was used to capture and compute ROM of the TWA components. Linear regression assessed the associations between alignment and outcomes.

Results Radiographic measures had a 95% limit-of-agreement (mean difference ±  1.96 × SD) of 3 degrees and 3mm with three-dimensional values, except for the measures of the carpal component in the lateral view. In our small cohort, wrist flexion–extension and radial–ulnar deviation were correlated with volar–dorsal tilt and volar–dorsal offset of the radial component and demonstrated a ROM increase of 3.7 and 1.6 degrees per degree increase in volar tilt, and 10.8 and 4.2 degrees per every millimeter increase in volar offset. The carpal component's higher volar tilt was also associated with improvements in patient-reported pain.

Conclusions We determined metrics describing the alignment of TWA, and found the volar tilt and volar offset of the radial component could potentially influence the replaced wrist's ROM.

Clinical Relevance TWA component alignment can be measured reliably in radiographs, and may be associated with clinical outcomes. Future studies must evaluate its role in a larger cohort.
A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia
Authors: Ciaccio Claudia , Leonardi Emanuela , Polli Roberta , Murgia Alessandra , D'Arrigo Stefano , Granocchio Elisa , Chiapparini Luisa , Pantaleoni Chiara , Esposito Silvia
Published: April 2021

KIRREL3 is a gene important for the central nervous system development—in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis—and colocalizes and cooperates in neurons with CASK gene. Alterations of KIRREL3 have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of KIRREL3 partially penetrating variants, and a recessive inheritance pattern. We report a novel and de novo KIRREL3 mutation in a child affected by severe neurodevelopmental disorder and with brain magnetic resonance imaging evidence of mega cisterna magna and mild cerebellar hypoplasia. This case strengthens the hypothesis that dominant KIRREL3 variants may lead to neurodevelopmental disruption; furthermore, given the strong interaction between KIRREL3 and CASK, we discuss as posterior fossa anomalies may also be part of the phenotype of KIRREL3-related syndrome.
Clinical Repurposing of Medicines is Intrinsic to Homeopathy: Research Initiatives on COVID-19 in India
Authors: Varanasi Roja , Nayak Debadatta , Khurana Anil
Published: April 2021

As at mid-October 2020, the coronavirus disease 2019 (COVID-19) pandemic has been continuing on the rise across the globe, including in India. Historically, homeopathy has been used in a number of epidemics/pandemics. The development of homeopathic medicines is approached uniquely through “drug provings” and clinical verification; these two intrinsic processes establish the background for the application of homeopathic medicines, regardless of nosological diagnosis. This article reflects research initiatives on COVID-19 in India and identifies studies listed in the Clinical Trial Registry–India database. We identified 29 studies being undertaken in different settings, including those in conventional medicine: 20 randomized controlled trials (RCTs) and 9 observational studies. Fifteen studies are aimed at prophylaxis and 14 are aimed at treatment. Amongst the treatment studies, 11 are focused on efficacy or comparative effectiveness. The findings might provide evidence for clinically repurposing some of homeopathy's medicines, an approach that is intrinsic to the therapy, enabling their use in COVID-19 as an adjuvant or stand-alone to help reduce costs and improve patient recovery.
Birth and Growth of Neuroimaging and Vascular Intervention at Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram—Part I
Authors: Vedula Rajanikanth Rao , Kolathu Ravi Mandalam
Published: April 2021

This article is a historical narrative that traces the growth of neuroradiology and interventional radiology at the Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram. From its humble origins in the pre-CT scan era of the mid and late 1970s, when invasive diagnostic procedures such as percutaneous carotid angiography, myelography, pneumoencephalography (PEG) and ventriculography were the mainstay of neuroimaging, the authors take the reader through their gradual foray into catheter four-vessel angiography and later free-flow embolization of arteriovenous malformations (AVMs), and finally to the use of microcatheters for selective embolization procedures. The equipment used in those early years—fluoroscopic tilting table, roll-film cameras, serial changers, PEG tables—provide an insight to an era with all its challenges before the advent of digital imaging. The authors’ efforts to indigenize some of the hardware such as metallic stents and embolization material such as hydrogel spheres and lyophilized dura are also highlighted. The development of peripheral vascular intervention alongside neuroradiology is also highlighted. The authors pay tribute to an early pioneer of neuroradiology in India, Prof. Mahadevan Pillai, who was a guiding light to them during those nascent years.
Brain Injury in Extracorporeal Membrane Oxygenation: A Multidisciplinary Approach
Authors: Chiarini Giovanni , Cho Sung-Min , Whitman Glenn , Rasulo Frank , Lorusso Roberto
Published: April 2021

Extracorporeal membrane oxygenation (ECMO) represents an established technique to provide temporary cardiac and/or pulmonary support. ECMO, in veno-venous, veno-arterial or in extracorporeal carbon dioxide removal modality, is associated with a high rate of brain injuries. These complications have been reported in 7 to 15% of adults and 20% of neonates, and are associated with poor survival. Thromboembolic events, loss of cerebral autoregulation, alteration of the blood–brain barrier, and hemorrhage related to anticoagulation represent the main causes of severe brain injury during ECMO. The most frequent forms of acute neurological injuries in ECMO patients are intracranial hemorrhage (2–21%), ischemic stroke (2–10%), seizures (2–6%), and hypoxic–ischemic brain injury; brain death may also occur in this population. Other frequent complications are infarction (1–8%) and cerebral edema (2–10%), as well as neuropsychological and psychiatric sequelae, including posttraumatic stress disorder.
Factors Associated with Umbilical Venous Catheter Malposition in Newborns: A Tertiary Center Experience
Authors: Soonsawad Sasivimon , Kieran Emily A. , Ting Joseph Y. , AlonsoPrieto Esther , Panczuk Julia K.
Published: April 2021

Objective Umbilical venous catheters (UVC) are widely used in neonatal intensive care (NICU). Noncentral catheter position is known to be associated with multiple adverse complications; however, risk factors for catheter malposition are unclear. This work aimed to identify clinical risk factors and complications associated with UVC malposition in neonates admitted in an NICU.

Study Design A retrospective chart review was performed of inborn babies admitted to BC Women's Hospital NICU with UVC inserted in their first 7 days between July 2016 and June 2018. Infant and maternal demographic, radiograph, UVC-related data, and complications were reviewed.

Results A total of 257 infants had UVC placed; 158 (61%) and 99 (39%) were in central and noncentral positions after initial placement, respectively. Of initially central-placed UVCs, a further 35 (22%) were pulled back or migrated to malposition on follow-up X-ray. Multivariable logistic regression analysis revealed the use of larger UV (5 Fr) catheter (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.1–5.6, p = 0.026) and escalation of respiratory support mode (OR: 1.7, 95% CI: 1.0–2.8, p = 0.049) as significant predictors of catheter malposition.

Conclusion Noncentral UVC position as well as migration were common after initial placement in this cohort. The use of larger size UV catheters and increasingly invasive respiratory support were risk factors associated with higher incidence of UVC malposition. Ongoing surveillance of UVC position is thus recommended.

Key Points
Reconstruction of the Anterior Cruciate Ligament Using Ruler-Assisted Positioning of the Femoral Tunnel Relative to the Posterior Apex of the Deep Cartilage: A Single-Center Case Series
Authors: Dong Yan , Tang Jiaguang , Cui Peng , Shen Songpo , Wang Guodong , Li Jian , Kong Xiaochuan , Hong Gang , Yuan Shuo , Zang Lei
Published: April 2021

The techniques available to locate the femoral tunnel during anterior cruciate ligament (ACL) reconstruction have notable limitations. To evaluate whether the femoral tunnel center could be located intraoperatively with a ruler, using the posterior apex of the deep cartilage (ADC) as a landmark. This retrospective case series included consecutive patients with ACL rupture who underwent arthroscopic single-bundle ACL reconstruction at the Department of Orthopedics, Beijing Tongren Hospital between January 2014 and May 2018. During surgery, the ADC of the femoral lateral condyle was used as a landmark to locate the femoral tunnel center with a ruler. Three-dimensional computed tomography (CT) was performed within 3 days after surgery to measure the femoral tunnel position by the quadrant method. Arthroscopy was performed 1 year after surgery to evaluate the intra-articular conditions. Lysholm and International Knee Documentation Committee (IKDC) scores were determined before and 1 year after surgery. The final analysis included 82 knees of 82 patients (age = 31.7 ± 6.1 years; 70 males). The femoral tunnel center was 26 ± 1.5% in the deep-shallow (x-axis) direction and 31 ± 3.1% in the high-low (y-axis) direction, close to the “ideal” values of 27 and 34%. Lysholm score increased significantly from 38.5 (33.5–47) before surgery to 89 (86–92) at 1 year after surgery (p < 0.001). IKDC score increased significantly from 42.5 (37–47) before surgery to 87 (83.75–90) after surgery (p < 0.001). Using the ADC as a landmark, the femoral tunnel position can be accurately selected using a ruler.
Outcomes of Total Knee Arthroplasty in Patients with Prior Hardware: A Case–Control Study Using Handheld Navigation
Authors: Malhotra Rajesh , Jain Aditya , Gupta Saurabh , Gautam Deepak
Published: April 2021

Presence of hardware in juxta-articular location poses challenge during total knee arthroplasty (TKA). When present in distal femur, it precludes the use of an intramedullary femoral jig during TKA often necessitating removal of hardware leading to prolonged surgery, higher risk of complications, and inferior results. We conducted a case–control study to assess the outcome of TKA among patients with post-traumatic arthritis using a handheld navigation system to perform bone cuts allowing retention of hardware in situ. In 15 patients with post-traumatic arthritis and hardware around the knee (Group A), none or part(s) of hardware were removed while performing TKA. These patients were matched to 15 patients who underwent TKA with handheld navigation for primary OA knee (Group B). The perioperative outcomes assessed were operative time, intraoperative blood loss, length of hospital stay, complications, and 30 days reoperation rate. Clinical outcomes were assessed by using Knee Society Score (KSS) and radiological outcomes using mechanical axis and coronal and sagittal component angles. Mean age of patients at surgery were 65.67 years (Group A) and 66.73 years (Group B). Mean operative time and blood loss were significantly higher in Group A as compared with Group B. At the mean follow-up of 34 months, KSS significantly improved in both the groups. However, there was no statistically significant difference in the clinical and radiological outcomes between the two groups. One patient in Group A developed wound dehiscence and had to undergo debridement and flap coverage within 30 days. The use of navigation helps surgeons in gaining proper limb alignment and implant positioning without complete removal of hardware.
Biomechanical Evaluation of Anterolateral Ligament Repair Augmented with Internal Brace
Authors: Roach Ryan P. , Beason David P. , Slowik Jonathan S. , Moore A. Ryves , Lall Ajay C. , Dugas Jeffrey R.
Published: April 2021

Injuries to the anterolateral ligament (ALL) of the knee are commonly associated with anterior cruciate ligament (ACL) ruptures. Biomechanical studies have demonstrated conflicting results with regard to the role of the ALL in limiting tibial internal rotation. Clinically, residual pivot shift following ACL reconstruction has been reported to occur up to 25% and has been correlated with poor outcomes. As such, surgical techniques have been developed to enhance rotational stability. Recent biomechanical studies have demonstrated restoration of internal rotational control following ALL reconstruction. The purpose of our study was to understand the biomechanical effects of ACL reconstruction with an ALL internal brace augmentation. We hypothesized that (1) sectioning of the ALL while preserving other lateral extra-articular structures would lead to significant internal rotation laxity and gap formation and (2) ALL repair with internal brace augmentation would lead to reduction in internal rotation instability and gap formation. In total, 10 fresh-frozen cadaveric knees were thawed and biomechanically tested in internal rotation for 10 cycles of normal physiologic torque in the intact, ACL-deficient, ACL/ALL-deficient, ACL-reconstructed, and ALL-repaired conditions. Each condition was tested at 30, 60, and 90 degrees of flexion. Following the final ALL-repaired condition, specimens were additionally subjected to a final internal rotation to failure at 1 degree at the last-tested degree of flexion. Kinematic measurements of angle and linear gap between the femur and tibia were calculated in addition to torsional stiffness and failure torque. As hypothesized, ALL repair with internal brace augmentation significantly reduced internal rotation angular motion and gap formation at flexion angles greater than 30 degrees. Additionally, ALL sectioning produced nonsignificant increases in internal rotation laxity and gap formation compared with ACL-deficient and ACL-reconstructed states, which did not support our other hypothesis.
Complicated Monochorionic–Diamniotic Twins in a Pregnant Woman with COVID-19 in the Second Trimester
Authors: Mok Thalia , Contreras Deisy , Chmait Ramen H. , Goldstein Jeffrey , Pluym Ilina D. , Tabsh Khalil , Aldrovandi Grace , Afshar Yalda
Published: April 2021

Objective A majority of studies evaluating the risk of vertical transmission and adverse outcomes in pregnancies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mostly based on third-trimester infections. There is limited data available on pregnancy sequelae of maternal infection in the first or second trimester.

Study Design We present a patient with monochorionic–diamniotic twins that develops coronavirus disease 2019 infection at 15 weeks of gestation. The pregnancy is further complicated by stage II twin–twin transfusion syndrome. She undergoes laser ablation, which is complicated by development of a subchorionic hematoma. The patient then develops Escherichia coli bacteremia, resulting in septic shock and preterm labor followed by previable delivery at 21 weeks of gestation. Amniotic fluid and placenta were negative for SARS-CoV-2 by real-time polymerase chain reaction.

Conclusion This case of SARS-CoV-2 argues against transplacental transmission after a second-trimester infection but brings attention to the possible downstream complications that may arise following early infection.

Key Points
Mother–Infant Dyads with COVID-19 at an Urban, Safety-Net Hospital: Clinical Manifestations and Birth Outcomes
Authors: Sabharwal Vishakha , Bartolome Ruby , Hassan Sacha Al , Levesque Bernadette M. , Camelo Ingrid Y. , Wachman Elisha M. , Figueira Marisol , Yarrington Christina D. , Cooper Ellen R. , Barnett Elizabeth D. , Parker Margaret G.
Published: April 2021

Objective This study aimed to describe maternal characteristics and clinical outcomes of infants born to mothers with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests during pregnancy at an urban, safety-net hospital in Boston.

Study Design We abstracted electronic chart data from 75 pregnant women with positive SARS-CoV-2 tests at any stage of gestation until 72 hours after birth who delivered consecutively between March 31 and August 6, 2020 at our center. We collected clinical data on maternal and infant characteristics, including testing, signs, and symptoms of coronavirus disease 2019 (COVID-19), delivery outcomes, newborn care practices (skin-to-skin care, location of care, and breastfeeding) and 30-day postdischarge infant emergency room visits and readmissions. We described categorical characteristics as percentages for this case series.

Results Among 75 pregnant women, 47 (63%) were Hispanic, 10 (13%) had hypertension, 23 (30%) had prepregnancy obesity, and 57 (76%) had symptomatic SARS-CoV-2 infection. Regarding birth outcomes, 32 (41%) had cesarean delivery and 14 (19%) had preterm birth. Among 75 infants, 5 (7%) had positive SARS-CoV-2 polymerase chain reaction tests in the first week of life, all of whom were born to Hispanic mothers with symptomatic SARS-CoV-2 infection and had clinical courses consistent with gestational age. Six (8%) infants visited the emergency department within 30 days of discharge; one was admitted with a non-COVID-19 diagnosis.

Conclusion At our urban, safety-net hospital among pregnant women with positive SARS-CoV-2 tests, 41% had a cesarean delivery and 19% had a preterm birth. Seven percent of infants had one or more positive SARS-CoV-2 tests and all infants had clinical courses expected for gestational age.

Key Points
Risk Factors for Surgical Site Infections in Pediatric General Surgery: A Case–Control Study
Authors: Almogbel Gassan T. , Altokhais Tariq I. , Alhothali Abdulaziz , Aljasser Abdulaziz Sami , Al-Qahtani Khalid M. , Arab Sadiq F. , Alsweirki Helmi M. H. , Albassam Abdulrahman
Published: April 2021

Objective Despite being the most common postoperative complication and having associated morbidity and mortality that increase health care costs, surgical site infection (SSI) has not received adequate attention and deserves further study. Previous reports in children were limited to SSI in certain populations. We conducted this retrospective case–control study to determine the incidence and possible risk factors for SSI following pediatric general surgical procedures.

Methods This was a retrospective case–control matched cohort study of all patients aged 0 to 14 years who underwent pediatric general surgical procedures between June 2015 and July 2018. The electronic medical records were searched for a diagnosis of SSI. Control subjects were randomly selected at a 4:1 ratio from patients who underwent identical procedures. Multiple risk factors were evaluated by bivariate analysis and multivariable conditional logistic regression.

Results A total of 1,520 patients underwent a general pediatric procedure during the study period, and of these, 47 (3.09%) developed SSIs. A bivariate analysis showed that patients with SSIs were younger, were admitted to the neonatal intensive care unit/pediatric intensive care unit (NICU/PICU) preoperatively, were more severely ill as measured by the ASA classification, underwent multiple procedures, had more surgical complications, and were transferred to the NICU/PICU postoperatively. A multivariate analysis identified four independent predictors of SSI: age, preoperative NICU/PICU admission, number of procedures, and ASA classification.

Conclusion Younger children with preoperative admission to the NICU/PICU, those who underwent multiple procedures and those who were severely ill as measured by their ASA classification were significantly more likely to develop SSIs.
Massively Parallel Sequencing of 43 Arrhythmia Genes in a Selected SUDI Cohort from Cape Town
Authors: Heathfield Laura Jane , Watkins Hugh , Martin Lorna Jean , Ramesar Raj
Published: April 2021

Sudden unexpected death in infants (SUDI) is a devastating event, and unfortunately occurs frequently in developing countries. The emerging molecular autopsy has added value to post-mortem investigations, where genetic variants were able to explain the unexpected demise. Many of these variants have been found in genes involved in arrythmia pathways. The aim of this study was to sequence 43 genes previously associated with cardiac arrhythmia in a selected cohort of SUDI cases (n = 19) in South Africa. A total of 335 variants were found among the 19 infants, of which four were novel. The variants were classified as “likely pathogenic” (n = 1), “variant of unknown significance” (n = 54), “likely benign” (n = 56) or “benign” (n = 224). The likely pathogenic variant was LMNA NM_170707.2:c.1279C > T (p.Arg427Cys) and was found in a 3-week-old male infant of African ancestry. Variants in LMNA have previously been associated with dilated cardiomyopathy, with a typical age of onset in adulthood; therefore, this may be the first report in an infant. The yield of pathogenic or likely pathogenic variants in the classic genes typically associated with channelopathies and sudden death, was less in this study compared with other settings. This finding highlights the importance of population-specific research to develop a molecular autopsy which is locally relevant.
Preoperative Determination of the Size of the Semitendinosus and Gracilis Tendon by Multidetector Row CT Scanner for Anterior Cruciate Ligament Reconstruction
Authors: Truong Pham N. , Toan Ngo V. , Nam Vũ H. , Fang William H. , Vangsness Jr C. Thomas , Han Bo , Hoang Ba X.
Published: April 2021

Accurately measuring the length and diameter of the hamstring tendon autograft preoperatively is important for planning anterior cruciate ligament (ACL) reconstructive surgery. The purpose of this study was to assess the reliability of three-dimensional computed tomography (3D CT) scanning technique to produce the actual measurement of the gracilis and semitendinosus (GT and ST, respectively) tendon grafts' length and diameter for surgery. Ninety patients were scheduled for ACL reconstruction with hamstring autograft. Before the surgery, patients were examined under the multidetector row CT scanner and the ST and GT tendons were qualitatively measured by a volume-rendering technique. The length of ST and GT was measured with 3D CT compared with the length of the harvested ST and GT. The cross-sectional area (CSA) of ST and GT measured with 3D CT compared with the ST and GT graft diameter. Tendon size measured preoperatively and during surgery were statistically compared and correlated. The GT tendons length and cross-sectional area measured during surgery was both shorter and smaller compared with the ST tendon. GT and ST tendon length were correlated to patients' body index such as the height and weight (p < 0.05). However, the correlation levels were low to medium (r = 0.23–0.49). There was strong correlation between the lengths of GT (r = 0.76; p < 0.001) and ST (r = 0.87; p < 0.001) measured with the 3D CT and tendon length at surgery. There was a moderate correlation between graft diameter measured at surgery and 3D CT cross-sectional area (r = 0.31; p < 0.05). A multidetector row CT scanner can determine the ST and GT tendons' length and diameter. These measurements can be used for preoperative planning to help determine the surgical method and counsel patients on appropriate graft choices prior to surgery.