bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic approaches to gastroesophageal reflux disease
Authors: Zhang Linda Yun , Canto Marcia Irene
Published: July 2021

Purpose of review

Gastroesophageal reflux disease (GERD) is one of the most common chronic conditions affecting adults. A substantial proportion of patients continue to have symptoms despite medical therapy, and there has been increased demand for minimally invasive GERD therapy. We will examine currently available techniques and outcomes data on endoscopic approaches to the treatment of GERD.

Recent findings

In the last 2 years, research has given rise to more robust understanding of not only the pathophysiology of GERD but also how to better manage the various phenotypes. We are learning the ideal patient to benefit from endoscopic GERD therapy. In this review, we describe the four major endoluminal techniques for treating GERD and summarize current data.

Endoscopic therapies are well positioned to fill the ‘therapy gap’ between medical therapy and more invasive surgical procedures.
Significance and management of isolated distal deep vein thrombosis
Authors: Makedonov Ilia , Galanaud Jean-Philippe , Kahn Susan R.
Published: July 2021

Purpose of review

Management of isolated distal deep vein thrombosis (IDDVT) remains controversial. We summarize recent studies regarding the natural history of IDDVT as well as pertinent therapeutic trials. We also provide our management approach.

Recent findings

IDDVT is more commonly associated with transient risk factors and less often associated with permanent, unmodifiable risk factors than proximal DVT. IDDVT has a significantly lower risk of proximal extension and recurrence than proximal DVT. Cancer-associated IDDVT has a similar natural history to cancer-associated proximal DVT, with substantially less favourable outcomes than noncancer-associated IDDVT. Anticoagulant treatment reduces the risk of proximal extension and recurrence in IDDVT at the cost of increased bleeding risk. Intermediate dosing of anticoagulation may be effective for treating noncancer-associated IDDVT in patients without prior DVT.

IDDVT with a transient risk factor can be treated for 6 weeks in patients without a prior DVT. Unprovoked IDDVT in patients without malignancy can be treated for 3 months. Outpatients without malignancy or a prior DVT can be left untreated and undergo surveillance compression ultrasound in one week to detect proximal extension, but few patients opt for this in practice. Cancer-associated IDDVT should be treated analogously to cancer-associated proximal DVT.
Next generation epigenetic modulators to target myeloid neoplasms
Authors: Sasca Daniel , Guezguez Borhane , Kühn Michael W.M.
Published: July 2021

Purpose of review

Comprehensive sequencing studies aimed at determining the genetic landscape of myeloid neoplasms have identified epigenetic regulators to be among the most commonly mutated genes. Detailed studies have also revealed a number of epigenetic vulnerabilities. The purpose of this review is to outline these vulnerabilities and to discuss the new generation of drugs that exploit them.

Recent findings

In addition to deoxyribonucleic acid-methylation, novel epigenetic dependencies have recently been discovered in various myeloid neoplasms and many of them can be targeted pharmacologically. These include not only chromatin writers, readers, and erasers but also chromatin movers that shift nucleosomes to allow access for transcription. Inhibitors of protein-protein interactions represent a novel promising class of drugs that allow disassembly of oncogenic multiprotein complexes.

An improved understanding of disease-specific epigenetic vulnerabilities has led to the development of second-generation mechanism-based epigenetic drugs against myeloid neoplasms. Many of these drugs have been introduced into clinical trials and synergistic drug combination regimens have been shown to enhance efficacy and potentially prevent drug resistance.
Prothrombotic state associated with preeclampsia
Authors: Han Cha , Chen Yuan-Yuan , Dong Jing-fei
Published: July 2021

Purpose of review

Preeclampsia is a common complication of pregnancy and contributes significantly to maternal and fetal morbidity and mortality. A protective hypercoagulable state is often developed during late pregnancy and can evolve into a prothrombotic state in patients with preeclampsia. The underlying mechanism of this prothrombotic transition remains poorly understood. We discuss recent progress in understanding the pathophysiology of preeclampsia and associated prothrombotic state.

Recent findings

The hypercoagulable state developed during pregnancy is initiated by placental factors and progresses into the prothrombotic state in preeclampsia when the placenta is subjected ischemic and oxidative injuries. The cause of the preeclampsia-induced prothrombotic state is multifactorial, involving not only placental factors but also maternal conditions, which include genetic predisposition, preexisting medical conditions, and conditions acquired during pregnancy. Endotheliopathy is the primary pathology of preeclampsia and contributes to the prothrombotic state by inducing the dysregulation of coagulation, platelets, and adhesive ligands.

Patients with preeclampsia often develop a severe prothrombotic state that predisposes them to life-threatening thrombosis and thromboembolism during and after pregnancy. Early recognition and treatment of this prothrombotic state can improve maternal and infant outcomes of preeclampsia patients.
Gut Microbiota Composition of Biliary Atresia Patients Before Kasai Portoenterostomy Associates With Long-term Outcome
Authors: van Wessel Daan , Nomden Mark , Bruggink Janneke , de Kleine Ruben , Kurilshikov Alexander , Verkade Henkjan , Harmsen Hermie , Hulscher Jan
Published: July 2021

Background and Aims:

Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, that is, the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE.

Methods:

We compared feces of term-born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ versus without COJ (total serum bilirubin < or ≥20 μmol/L <6 months post-KPE).

Results:

Alpha diversity was comparable between BA (n = 12, age 1.6 [1.3–1.8] months) and controls (n = 6, age 2.0 [1.4–2.1] months; P = 0.22). Compared with controls, BA patients had lower abundances of Bifidobacteriaceae (β = −1.98, P < 0.001) and Lachnospiraceae (β = −1.84, P = 0.007), and higher abundances of Streptococcus (β = −1.13, P = 0.003). The alpha diversity before KPE correlated negatively with COJ (R = −0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (βlogit = −0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β = 1.27, P = 0.03) and family Clostridiaceae (β = 1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae (genera Klebsiella (β = −1.21, P = 0.01), Salmonella (β = −1.57, P = 0.02)) in COJ [+] versus COJ [−].

Conclusions:

The GM of BA patients before Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive, and mechanistic roles of the gut microbiota composition in bile homeostasis.
Sarcopenia in patients following stroke: an overlooked problem
Authors: Aydin Tuğba , Kesiktaş Fatma Nur , Oren Meryem Merve , Erdogan Tugba , Ahisha Yiğit Can , Kizilkurt Taha , Corum Mustafa , Karacan İlhan , Öztürk Savaş , Bahat Gulistan
Published: July 2021

Our aim was to investigate the prevalence of sarcopenia in stroke patients, the relationship between sarcopenia detected with different low muscle mass (LMM) adjustment methods, and between stroke-related parameters. Eighty-one patients with chronic stroke who underwent inpatient rehabilitation were included. Spasticity was evaluated by modified Ashworth scale, Brunnstrom staging approach was used for motor function evaluation, physical independence was evaluated using Barthel Index, quality-of-life was evaluated by EQ-5D-3L, and the Cumulative Illness Rating Scale was used to measure multimorbidity. Muscle strength was evaluated by handgrip strength, muscle quantity through a bioelectric impedance analysis, and physical performance by gait speed and short physical performance battery. LMM was calculated through two different methods: Skeletal muscle mass (SMM)/height2, and SMM/BMI. For the definition of sarcopenia, we followed the EWGSOP2 recommendation. Associated sarcopenia factors were predicted by multivariate binary logistic regression analysis. The prevalence of probable sarcopenia was 32.1%. The prevalence of confirmed/sarcopenia when LMM was adjusted for BMI was higher than when adjusted for height2 (16 and 1.2%, respectively). Age was significantly higher in those with probable sarcopenia (P = 0.006). Stroke duration was shorter in those with probable or confirmed sarcopenia (P = 0.004, P < 0.001, respectively). EQ-5D-3L scores were significantly lower in those with confirmed sarcopenia (P = 0.050). The strongest associated factor with confirmed sarcopenia was stroke duration (OR: 0.77; 95% CI, 0.618–0.965). This study suggests that prevalence of sarcopenia after a stroke is significantly high. LMM adjusted for BMI comes in front as the adjustment method for LMM after a stroke.
Nodular Maturation of the Testis
Authors: Przybycin Christopher G. , Williamson Sean R. , Kao Chia-Sui , Reyes-Múgica Miguel , Ulbright Thomas M. , McKenney Jesse K.
Published: July 2021

We have encountered a lesion of the pediatric testis, termed “nodular maturation,” that clinically mimics a testicular neoplasm causing ultrasound abnormalities that may lead to surgical excision. To our knowledge, it has only been described anecdotally in textbooks without a series or description in the literature. We, therefore, report 8 cases in pediatric patients emphasizing the clinical presentation, ultrasound findings, histologic features, and clinical follow-up information. Patients ranged in age from 5 to 11 years (mean: 7.9 y). Precocious puberty was identified in 1 patient as isolated penile enlargement without other signs; another had a history of McCune-Albright syndrome, but did not have signs of precocious puberty; others had no clinical manifestations. All patients had testicular abnormalities on ultrasound; 6 had a discrete lesion and 2 showed diffuse testicular enlargement. In the 6 cases with available data, mean size of the lesion on ultrasound was 0.9 cm (range: 0.4 to 1.7 cm). In the 3 cases for which macroscopic descriptions were available, no gross abnormalities were noted in the testicular parenchyma, despite the ultrasound findings. Histologically, nodular maturation occurred as a zone of more mature testicular parenchyma having larger, lumen-bearing seminiferous tubules that contrasted with the smaller, immature cords of the remaining parenchyma. The mature tubules showed germ cell maturation (to the level of late spermatids/spermatozoa in 6 cases), mature Sertoli cells, and, in 4 cases, admixed nodules of mature Leydig cells. Of the 6 patients with available follow-up information, none developed a testicular neoplasm. Given its ability to cause a lesion on ultrasound leading to surgical intervention, pathologists, radiologists, and urologists should be aware of nodular maturation.
Pediatric Trauma
Authors: Perea Lindsey L. , Echeverria Rosario Karla , Staman Stacey , Fox Nicole
Published: July 2021

Objectives

Pediatric trauma patients are injured during crucial developmental years and require subsequent absence from school and activities. The impact of these changes on pediatric trauma patients is not well studied. We sought to assess the functional and emotional impact of pediatric trauma. In addition, the inpatient experience was evaluated for performance improvement purposes.

Methods

A prospective survey was conducted at our trauma center (February 2019 to May 2019) of admitted trauma patients (<18 years). Patients who died before admission and nonaccidental trauma patients were excluded. Patients completed an inpatient survey and another at 3 months postdischarge.

Results

Sixty patients were enrolled; 31 completed follow-up. Patients were 10 ± 5 years, 75% being male (n = 45), with an Injury Severity Score of 7 ± 6. A total of 13% were seen by behavioral medicine while inpatient; 18% of patients had preexisting anxiety. Preexisting functional limitations existed in 7% of the patients. At 3 months, 71% were back to preinjury academics, and 58% had returned to extracurriculars. At follow-up, 10% of patients felt withdrawn, and 32% felt emotional/distracted. Only 13% of patients were undergoing therapy compared with 7% preinjury. Patients communicated their best/worst experiences.

Conclusion

Pediatric trauma patients experience significant functional and emotional limitations after trauma. This suggests that all pediatric trauma patients should be evaluated by behavioral medicine during their admission with postdischarge support services offered. Performance improvement opportunities were identified in areas of pain control and communication.
Not Seeing Double: Discordance in Disease, Function, and Their Longitudinal Associations in Monozygotic Twins
Authors: Teas Elizabeth , Robertson Olivia , Marceau Kristine , Friedman Elliot
Published: July 2021

Objective

Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being.

Methods

The twin subsample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (wave 1, 1995–1996; wave 2, 2004–2006). Only monozygotic twins (n = 713) were included in analyses. In separate multilevel models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1.

Results

Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = 0.40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = 0.06, p = .02). Well-being was not a moderator in either model.

Conclusions

We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.
Direct Verbal Suggestibility as a Predictor of Placebo Hypoalgesia Responsiveness
Authors: Parsons Ryan D. , Bergmann Sofia , Wiech Katja , Terhune Devin B.
Published: July 2021

Objective

Reliably identifying good placebo responders has pronounced implications for basic research on, and clinical applications of, the placebo response. Multiple studies point to direct verbal suggestibility as a potentially valuable predictor of individual differences in placebo responsiveness, but previous research has produced conflicting results on this association.

Methods

In two double-blind studies, we examined whether behavioral direct verbal suggestibility measures involving a correction for compliance would be associated with individual differences in responsiveness to conditioned and unconditioned placebo hypoalgesia using an established placebo analgesia paradigm. In study 1 (n = 57; mean [standard deviation] age = 23.7 [8.1] years; 77% women), we used behavioral hypnotic suggestibility as a predictor of placebo hypoalgesia induced through conditioning and verbal suggestion, whereas in study 2 (n = 78; mean [standard deviation] = 26.1 [7.4] years; 65% women), we measured nonhypnotic suggestibility and placebo hypoalgesia induced through verbal suggestion without conditioning.

Results

In study 1, the placebo hypoalgesia procedure yielded a moderate placebo response (g = 0.63 [95% confidence interval = 0.32 to 0.97]), but the response magnitude did not significantly correlate with hypnotic suggestibility (r
s = 0.11 [−0.17 to 0.37]). In study 2, the placebo procedure did not yield a significant placebo response across the full sample (g = 0.11 [−0.11 to 0.33]), but the magnitude of individual placebo responsiveness significantly correlated with nonhypnotic suggestibility (r
s = 0.27 [0.03 to 0.48]).

Conclusions

These results suggest that the extent to which direct verbal suggestibility captures variability in placebo responsiveness depends on the use of conditioning and highlights the utility of suggestibility as a potential contributing factor to placebo responding when placebo hypoalgesia is induced through verbal suggestions.
The Impact of Optimism and Pain Interference on Response to Online Behavioral Treatment for Mood and Anxiety Symptoms
Authors: Morone Natalia E. , Herbeck Bea Belnap , Huang Yan , Abebe Kaleab Z. , Rollman Bruce L. , Jonassaint Charles R.
Published: July 2021

Objective

This study aimed to explore a) if high pain interference has a negative effect on response to computerized cognitive behavioral therapy (cCBT) for anxiety and depression and b) whether high optimism can buffer the negative effects of pain interference on cCBT outcomes.

Methods

We performed a secondary analysis of data on 403 participants from the randomized controlled clinical trial “Online Treatment for Mood and Anxiety Disorders in Primary Care.” It examined the impact of cCBT, with and without access to an Internet support group, on health-related quality of life (HRQoL), mood, and anxiety symptoms.

Results

High versus low pain interference had a negative effect on response to cCBT for physical HRQoL regardless of high or low optimism level (between group difference = −3.46 [−5.89 to −1.03], p = .005, or −4.06 [−6.28 to −1.85], p < .001, respectively). However, in the context of low optimism/high pain interference only negatively impacted the effect of cCBT on mental HRQoL (3.68 [0.63 to 6.73], p = .018) and anxiety symptoms (−2.61 [−4.87 to −0.35], p = .024). Although the pattern of effects was similar for depressive symptoms, the between-group differences were not significant.

Conclusions

High optimism may buffer against the negative effects of pain interference on treatment response from cCBT. Primary care patients who report high pain interference yet also lack optimism may not receive as much benefit from cCBT as other groups. Furthermore, this study found an unexpected positive effect of low optimism on treatment response. For depressed and anxious patients with low pain interference, low optimism enhanced the impact of cCBT on mental HRQoL.

Trial Registration:
ClinicalTrials.gov Identifier: NCT01482806.
Machine Learning and Deep Learning in Oncologic Imaging: Potential Hurdles, Opportunities for Improvement, and Solutions—Abdominal Imagers' Perspective
Authors: Yedururi Sireesha , Morani Ajaykumar C. , Katabathina Venkata Subbiah , Jo Nahyun , Rachamallu Medhini , Prasad Srinivasa , Marcal Leonardo
Published: July 2021

The applications of machine learning in clinical radiology practice and in particular oncologic imaging practice are steadily evolving. However, there are several potential hurdles for widespread implementation of machine learning in oncologic imaging, including the lack of availability of a large number of annotated data sets and lack of use of consistent methodology and terminology for reporting the findings observed on the staging and follow-up imaging studies that apply to a wide spectrum of solid tumors. This short review discusses some potential hurdles to the implementation of machine learning in oncologic imaging, opportunities for improvement, and potential solutions that can facilitate robust machine learning from the vast number of radiology reports and annotations generated by the dictating radiologists.
Orbital Plasmablastic Lymphoma
Authors: Bansal Himanshu , Ravina Mudalsha , Chandrakar Pradeep Kumar , Lukose Tinu Thadiyananickal , Krishna Sarin
Published: July 2021

Plasmablastic lymphoma (PBL) is a rare and aggressive variant of diffuse large B-cell lymphoma which is associated with HIV infection. Recently, it has also been reported in immunocompetent and solid organ transplant patients. PBL commonly presents in extranodal regions such as oral cavity, digestive tract, and skin. Orbital involvement by PBL is extremely rare with only few reports in the literature. We present a case of PBL involving the bilateral orbits in an immunocompetent patient with 1-year follow-up on 18F-FDG PET/CT scan.
Prevalence and Associated Risk Factors of Pulmonary Embolism in Children and Young Adults With Nephrotic Syndrome
Authors: Zhu Haitao , Qi Jianchen , Schoepf Joseph , Savage Rock H. , Tang Chunxiang , Lu Mengjie , Zhou Changsheng , Lu Guangming , Wang Dongqing , Zhang Longjiang
Published: July 2021

Purpose:

Nephrotic syndrome (NS) is highly associated with an increased risk of pulmonary embolism (PE) in children and young adults. However, few studies have specified the risk factors of PE in children and young adults with NS. We sought to determine the prevalence and associated factors of PE confirmed with computed tomography pulmonary angiography in Chinese children and young adults with NS.

Methods:

Data from 444 children and young adults with NS who had computed tomography pulmonary angiography from December 2010 to October 2018 were retrospectively analyzed. The prevalence of PE was estimated for different age, sex, and histopathologic types of NS. Multivariable logistic regression was used to identify independent risk factors of PE in children and young adults with NS. Models incorporating the independent risk factors were evaluated using receiver operation characteristic curves. Area under the curve was used to determine the best-performing prognosticators for predicting PE.

Results:

There were 444 patients in the study cohort (310 male patients, 134 female patients; mean age 19±3 y; range: 6 to 25 y). PE was present in 24.8% of the participants (110 of 444, 18.2% female). Children and young adult NS patients with PE tend to be older, male, to have a previous thromboembolism history and smoking, and have a higher level of proteinuria, D-dimer, and serum albumin (P<0.05 for all). Children and young adults with membranous nephropathy are likely to have a higher incidence of PE than those with other types of nephropathy. Membranous nephropathy and proteinuria were significant predictors of PE in children and young adults with NS (P<0.05 for all). The area under the curves of each model for the presence of PE in children and young adults with NS based on biochemical parameters and clinical information (model 1), adjusted for proteinuria (model 2), and adjusted for membranous nephropathy (model 3) were 0.578, 0.657, and 0.709, respectively. Compared with model 1, model 2, and model 3 showed statistically significant differences (model 1 vs. model 2, P=0.0336; model 1 vs. model 3, P=0.0268). There was no statistically significant difference between model 2 and model 3 (P=0.2947).

Conclusion:

This study identified membranous nephropathy and proteinuria as independent associated factors of PE in children and young adults with NS, which can be noted as a risk factor to guide clinician management in this population.
Partition of Pectoralis Major Musculocutaneous Flap as a Salvage Procedure for Simultaneous Coverage of the Exposed Carotid Artery and Reconstruction of Cervical Esophagus
Authors: Bolletta Alberto , Losco Luigi , Lin Jason , Oh Christine , Di Taranto Giuseppe , Trignano Emilio , Cigna Emanuele , Chen Hung-Chi
Published: July 2021

Background

In advanced pharyngoesophageal cancer patients, a critical event is represented by the failure of primary reconstruction with exposure of the carotid artery and partial or total defect of the cervical esophagus. For these high-risk patients, a partitioned pectoralis major musculocutaneous (PMMC) flap can prevent carotid blowout and provide skin for simultaneous esophageal reconstruction.

Methods

Twenty-six patients needing pharyngoesophageal reconstruction together with coverage of carotid artery exposure were included in this retrospective case series. The patients were treated with a partitioned PMMC flap, based on the branching pattern of the pectoral branch of the thoracoacromial artery and the perforators of the pectoralis major muscle, to simultaneously reconstruct the defect and provide coverage for the carotid artery.

Results

In 25 patients, the partitioned PMMC flap reconstructions resulted in complete wound healing without occurrence of carotid blowout syndrome or fistula formation. Minor complications as partial flap necrosis (7.7%) and strictures formation (7.7%) were recorded but did not compromise reconstruction. Twenty-two patients were able to adopt a semisolid diet, and 4 had recurrence of cancer.

Conclusions

The partitioned PMMC flap reconstruction represents a useful salvage solution to simultaneously restore the continuity of the alimentary tract and provide reliable coverage for the exposed carotid artery.
Noninvasive Machine Learning Screening Model for Dacryocystitis Based on Ocular Surface Indicators
Authors: Song Xuefei , Li Lunhao , Han Fuchang , Liao Shenghui , Xiao Caiwen
Published: July 2021

Background:

Dacryocystitis is an orbital disease that can be easily misdiagnosed. The most common diagnostic tools for dacryocystitis are computed tomography, lacrimal duct angiography, and lacrimal tract irrigation. Yet, those are invasive methods, which are not conducive to extensive screening.

Objective:

To explore the significance of ocular surface indicators and demographic data in the screening of dacryocystitis.

Materials and Methods:

Data were prospectively collected from 56 patients with dacryocystitis (56 eyes) and 56 healthy individuals. Collected indicators included demographic information (gender, age), ocular surface data of tear meniscus height, objective scatter index (OSI), and clinical diagnosis. The model features were screened out by machine learning to establish a dacryocystitis screening model.

Results:

Tear meniscus height, OSI_maximum Lyapunov exponent, basic OSI, median of OSI, mean of OSI, slope coefficient of OSI linear regression, coefficient of variation in OSI, interquartile range of OSI, and other 8 parameters were used as model parameters to establish a dacryocystitis screening model with an overall detection accuracy of 85.71%.

Conclusions:

This new screening model that is based on ocular surface indicators provides a new option for noninvasive screening of dacryocystitis.
Appropriateness of Computed Tomography Scanning in the Diagnosis of Craniosynostosis
Authors: Margulies Ilana G. , Graziano Francis , Goel Pedram , Xu Hope , Bui Anthony H. , Brown Stav , Sanati-Mehrizy Paymon , Morgenstern Peter F. , Urata Mark M. , Taub Peter J.
Published: July 2021

Introduction:

Although physicians from a variety of specialties encounter infants with possible craniosynostosis, judicious use of computed tomography (CT) imaging is important to avoid unnecessary radiation exposure and healthcare expense. The present study seeks to determine whether differences in specialty of ordering physician affects frequency of resulting diagnostic confirmations requiring operative intervention.

Methods:

Radiology databases from 2 institutions were queried for CT reports or indications that included “craniosynostosis” or “plagiocephaly.” Patient demographics, specialty of ordering physician, confirmed diagnosis, and operative interventions were recorded. Cost analysis was performed using the fixed unit cost for a head CT to calculate the expense before 1 study led to operative intervention.

Results:

Three hundred eighty-two patients were included. 184 (48.2%) CT scans were ordered by craniofacial surgeons, 71 (18.6%) were ordered by neurosurgeons, and 127 (33.3%) were ordered by pediatricians. One hundred four (27.2%) patients received a diagnosis of craniosynostosis requiring operative intervention. Craniofacial surgeons and neurosurgeons were more likely than pediatricians to order CT scans that resulted in a diagnosis of craniosynostosis requiring operative intervention (P < 0.001), with no difference between craniofacial surgeons and neurosurgeons (P = 1.0). The estimated cost of obtaining an impact CT scan when ordered by neurosurgeons or craniofacial surgeons as compared to pediatricians was $2369.69 versus $13,493.75.

Conclusions:

Clinicians who more frequently encounter craniosynostosis (craniofacial and neurosurgeons) had a higher likelihood of ordering CT images that resulted in a diagnosis of craniosynostosis requiring operative intervention. This study should prompt multi-disciplinary interventions aimed at improving evaluation of pretest probability before CT imaging.
Analysis of the Effect of Weight Loss on Eustachian Tube Function by Transnasal Videoendoscopy
Authors: Eravci Fakih Cihat , Yildiz Bariş Doğu , Özcan Kürşat Murat , Moran Münevver , Çolak Mustafa , Karakuş Mehmet Fatih , Karakurt Süleyman Emre , Ikinciogullari Aykut , Dere Haci Hüseyin
Published: July 2021

Objective:

To investigate the effect of weight loss after bariatric surgery on eustachian tube (ET) function with video endoscopy.

Materials and Methods:

The present study was conducted as a prospective cohort and was completed with 19 patients. Three-step tympanometry (basal, Toynbee, Valsalva), dynamic slow-motion video endoscopy, and the Eustachian Tube Dysfunction Questionnaire-7 (ETDA-7) were applied to the patients preoperatively before bariatric surgery and in the postoperative 6th month. Dynamic slow-motion video endoscopy was graded between 0 and 3, or classified as patulous, as indicated in the literature.

Results:

The mean body mass index of 6 male and 13 female patients decreased from 47.3 ± 4.6 to 31.2 ± 5.4. Grade decline (median 2 ± 1) was experienced in all patients in DSVE, and 1 patient resulted as patulous ET. The ETDA-7 scores decreased in11 patients, remained stable in 7 patients, and increased in 1 patient with patulous ET. The statistical analysis of the preoperative and postoperative DSVE grading and ETDA-7 scores, excluding the patulous ET patient, was found to be significant (P 
= 0.001 and P 
= 0.003, respectively). There was no significant change in any of the tympanometry parameters (P > 0.05).

Conclusions:

Rapid weight loss with bariatric surgery results in an improvement in both the DSVE images and in the complaints of ET dysfunction in the majority of patients, but in some patients it may result in patulous ET. Therefore, preoperative evaluation of the ET with DSVE and questioning the patient's complaints are important in predicting patients who may develop patulous ET.
Local Control and Survival After Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma With Vascular Involvement
Authors: Jolissaint Joshua S. , Reyngold Marsha , Bassmann Jared , Seier Kenneth P. , Gönen Mithat , Varghese Anna M. , Yu Kenneth H. , Park Wungki , O’Reilly Eileen M. , Balachandran Vinod P. , D’Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Soares Kevin C. , Jarnagin William R. , Crane Christopher H. , Wei Alice C.
Published: July 2021

Objective:

We sought to compare overall survival (OS) and disease control for patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with ablative dose radiotherapy (A-RT) versus resection.

Summary Background Data:

Locoregional treatment for PDAC includes resection when possible or palliative RT. A-RT may offer durable tumor control and encouraging survival.

Methods:

This was a single-institution retrospective analysis of patients with PDAC treated with induction chemotherapy followed by A-RT [≥98 Gy biologically effective dose (BED) using 15–25 fractions in 3–4.5 Gy/fraction] or pancreatectomy.

Results:

One hundred and four patients received A-RT (49.8%) and 105 (50.2%) underwent resection. Patients receiving A-RT had larger median tumor size after induction chemotherapy [3.2 cm (undetectable-10.9) vs 2.6 cm (undetectable-10.7), P < 0.001], and were more likely to have celiac or hepatic artery encasement (48.1% vs 11.4%, P <0.001), or superior mesenteric artery encasement (43.3% vs 9.5%, P < 0.001); however, there was no difference in the degree of SMV/PV involvement (P = 0.123). There was no difference in locoregional recurrence/progression at 18-months between A-RT and resection; cumulative incidence was 16% [(95% confidence interval (CI) 10%–24%] versus 21% (95% CI 14%–30%), respectively (P
= 0.252). However, patients receiving A-RT had a 19% higher 18-month cumulative incidence of distant recurrence/progression [58% (95% CI 48%–67%) vs 30% (95% CI 30%–49%), P
= 0.004]. Median OS from completion of chemotherapy was 20.1 months for A-RT patients (95% CI 16.4–23.1 months) versus 32.9 months (95% CI 29.7–42.3 months) for resected patients (P < 0.001).

Conclusion:

Ablative radiation is a promising new treatment option for PDAC, offering locoregional disease control similar to that associated with resection and encouraging survival.
Neuromuscular junction disorders beyond myasthenia gravis
Authors: Oh Shin J.
Published: July 2021

Purpose of review

To give an overview of the recent data on three autoimmune neuromuscular junction disorders with the recent Food Drug Administration (FDA) approval of amifampridine [3,4-Diaminopyridine (3,4-DAP) and 3,4-diaminopyridine phosphate (3,4-DAPP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS).

Recent findings

In LEMS, the most important recent development is the introduction of FDA approved amifampridine for the symptomatic treatment. Randomized controlled studies showed an extremely effective improvement with amifampridine with daily dose of ≤ 80 mg with minimal side reactions. The next important development is in the electrodiagnostic criteria. Now 10 s exercise and an incremental response ≥ 60% either after 10 s exercise or at the high-rate stimulation in the repetitive nerve stimulation test are recommended as the standard tests.

In 2016, myasthenia-gravis Lambert-Eaton overlap syndrome (MLOS) was coined as new syndrome for patients with myasthenia gravis and LEMS combined symptoms in same patients.

In Isaacs syndrome, voltage gated calcium channel antibody order is no longer recommended because of low specificity for immunotherapy responsive disorders. Instead, ‘ leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated like-2 (CASPR2) autoantibody tests’ are recommended.

In LEMS, amifampridine (3,4 DAP and 3,4-DAPP) is approved by the FDA as an effective symptomatic treatment. MLOS is coined as new syndrome recently. In Isaacs syndrome, LGI1 and CASPR2 antibody tests are recommended.
Genetic therapy for congenital myopathies
Authors: Maani Nika , Karolczak Sophie , Dowling James J.
Published: July 2021

Purpose of review

There has been an explosion of advancement in the field of genetic therapies. The first gene-based treatments are now in clinical practice, with several additional therapeutic programs in various stages of development. Novel technologies are being developed that will further advance the breadth and success of genetic medicine.

Congenital myopathies are an important group of neuromuscular disorders defined by structural changes in the muscle and characterized by severe clinical symptoms caused by muscle weakness. At present, there are no approved drug therapies for any subtype of congenital myopathy.

In this review, we present an overview of genetic therapies and discuss their application to congenital myopathies.

Recent findings

Several candidate therapeutics for congenital myopathies are in the development pipeline, including ones in clinical trial. These include genetic medicines such as gene replacement therapy and antisense oligonucleotide-based gene knockdown. We highlight the programs related to genetic medicine, and also discuss congenital myopathy subtypes where genetic therapy could be applied.

Genetic therapies are ushering in an era of precision medicine for neurological diseases. Congenital myopathies are conditions ideally suited for genetic medicine approaches, and the first such therapies will hopefully soon be reaching congenital myopathy patients.
Variants of SARS-COV-2 and the Death Toll
Authors: Saito Takesi
Published: July 2021

New variants of SARS-COV-2 have been found in various countries. Especially, the UK has been attacked by India’s Delta Plus, and the spread of infection has been very rapid, since it is extremely infectious. Fortunately, however, the number of deaths has been stayed flat, where deaths are reported to be those who are not yet received a shot of COVID-19 vaccine. In this short not, we would like to consider why the number of deaths is so small, compared with high cases, around the infection peak, when the basic reproduction number is very large.
Polygenic Risk Prediction using Gradient Boosted Trees Captures Non-Linear Genetic Effects and Allele Interactions in Complex Phenotypes
Authors: Elgart Michael , Lyons Genevieve , Romero-Brufau Santiago , Kurniansyah Nuzulul , Brody Jennifer A. , Guo Xiuqing , Lin Henry J , Raffield Laura , Gao Yan , Chen Han , de Vries Paul , Lloyd-Jones Donald M. , Lange Leslie A , Peloso Gina M , Fornage Myriam , Rotter Jerome I , Rich Stephen S , Morrison Alanna C , Psaty Bruce M , Levy Daniel , Redline Susan ,   the NHLBI’s Trans-Omics in Precision Medicine (TOPMed) Consortium, Sofer Tamar
Published: July 2021

Polygenic risk scores (PRS) are commonly used to quantify the inherited susceptibility for a given trait. However, the standard PRS fail to account for non-linear and interaction effects between single nucleotide polymorphisms (SNPs). Machine learning algorithms can be used to account for such non-linearities and interactions. We trained and validated polygenic prediction models for five complex phenotypes in a multi-ancestry population: total cholesterol, triglycerides, systolic blood pressure, sleep duration, and height. We used an ensemble method of LASSO for feature selection and gradient boosted trees (XGBoost) for non-linearities and interaction effects. In an independent test set, we found that combining a standard PRS as a feature in the XGBoost model increases the percentage variance explained (PVE) of the prediction model compared to the standard PRS by 25% for sleep duration, 26% for height, 44% for systolic blood pressure, 64% for triglycerides, and 85% for total cholesterol. Machine learning models trained in specific racial/ethnic groups performed similarly in multi-ancestry trained models, despite smaller sample sizes. The predictions of the machine learning models were superior to the standard PRS in each of the racial/ethnic groups in our study. However, among Blacks the PVE was substantially lower than for other groups. For example, the PVE for total cholesterol was 8.1%, 12.9%, and 17.4% for Blacks, Whites, and Hispanics/Latinos, respectively. This work demonstrates an effective method to account for non-linearities and interaction effects in genetics-based prediction models.
Forecasts of weekly incident and cumulative COVID-19 mortality in the United States: A comparison of combining methods
Authors: Taylor Kathryn S. , Taylor James W.
Published: July 2021

Background

Forecasting models have played a pivotal role in health policy decision making during the coronavirus disease-2019 (COVID-19) pandemic. A combined forecast from multiple models will be typically more accurate than an individual forecast, but there are few examples of studies of combined forecasts of COVID-19 data, focusing mainly on simple mean and median ‘ensembles’ and involving short forecast evaluation periods. We aimed to investigate the accuracy of different ways of combining probabilistic forecasts of weekly COVID-19 mortality data, including two weighted methods that we developed previously, on an extended dataset and new dataset, and evaluate over a period of 52 weeks.

Methods

We considered 95% interval and point forecasts of weekly incident and cumulative COVID-19 mortalities between 16 May 2020 and 8 May 2021 in multiple locations in the United States. We compared the accuracy of simple and more complex combining methods, as well as individual models.

Results

The average of the forecasts from the individual models was consistently more accurate than the average performance of these models (the mean combination), which provides a fundamental motivation for combining. Weighted combining performed well for both incident and cumulative mortalities, and for both interval and point forecasting. Our inverse score with tuning method was the most accurate overall. The median combination was a leading method in the last quarter for both mortalities, and it was consistently more accurate than the mean combination for point forecasting. For interval forecasts of cumulative mortality, the mean performed better than the median. The best performance of the leading individual model was in point forecasting.

Conclusions

Combining forecasts can improve the contribution of probabilistic forecasting to health policy decision making during epidemics, and, when there are sufficient historical data on forecast accuracy, weighted combining provides the most accurate method.
An Open Repository of Real-Time COVID-19 Indicators
Authors: Reinhart Alex , Brooks Logan , Jahja Maria , Rumack Aaron , Tang Jingjing , Agrawal Sumit , Saeed Wael Al , Arnold Taylor , Basu Amartya , Bien Jacob , Cabrera Ángel A. , Chin Andrew , Chua Eu Jing , Clark Brian , Colquhoun Sarah , DeFries Nat , Farrow David C. , Forlizzi Jodi , Grabman Jed , Gratzl Samuel , Green Alden , Haff George , Han Robin , Harwood Kate , Hu Addison J. , Hyde Raphael , Hyun Sangwon , Joshi Ananya , Kim Jimi , Kuznetsov Andrew , Motte-Kerr Wichada La , Lee Yeon Jin , Lee Kenneth , Lipton Zachary C. , Liu Michael X. , Mackey Lester , Mazaitis Kathryn , McDonald Daniel J. , McGuinness Phillip , Narasimhan Balasubramanian , O’Brien Michael P. , Oliveira Natalia L. , Patil Pratik , Perer Adam , Politsch Collin A. , Rajanala Samyak , Rucker Dawn , Scott Chris , Shah Nigam H. , Shankar Vishnu , Sharpnack James , Shemetov Dmitry , Simon Noah , Smith Benjamin Y. , Srivastava Vishakha , Tan Shuyi , Tibshirani Robert , Tuzhilina Elena , Van Nortwick Ana Karina , Ventura Valérie , Wasserman Larry , Weaver Benjamin , Weiss Jeremy C. , Whitman Spencer , Williams Kristin , Rosenfeld Roni , Tibshirani Ryan J.
Published: July 2021

The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from de-identified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data is available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.
The impact of hypoxia on B cells in COVID-19
Authors: Kotagiri Prasanti , Mescia Federica , Hanson Aimee , Turner Lorinda , Bergamaschi Laura , Peñalver Ana , Richoz Nathan , Moore Stephen D , Ortmann Brian M , Dunmore Benjamin J. , Ruffieux Helene , Morgan Michael D , Tuong Zewen Kelvin , Bashford-Rogers Rachael J M , Hosmillo Myra , Baker Stephen , Elmer Anne , Goodfellow Ian G , Gupta Ravindra K. , Kingston Nathalie , Lehner Paul J. , Matheson Nicholas J. , Richardson Sylvia , Saunders Caroline , Weekes Michael P. ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens Berthold , Toshner Mark , Hess Christoph , Maxwell Patrick. H. , Clatworthy Menna. R. , Nathan James A. , Bradley John R. , Lyons Paul A. , Burrows Natalie , Smith Kenneth G.C.
Published: July 2021

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This brought to mind the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. We demonstrated the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes we also observed in B cell VHL-deficient mice. This was corroborated by hypoxia-related transcriptional changes in COVID-19 patients, and by similar B cell abnormalities in mice kept in hypoxic conditions, including reduced marginal zone and germinal center B cells. Thus hypoxia might contribute to B cell pathology in COVID-19, and in other hypoxic states. Through this mechanism it may impact on COVID-19 outcome, and be remediable through early oxygen therapy.
Monitoring of COVID-19 Pandemic-related Psychopathology using Machine Learning
Authors: Enevoldsen Kenneth C. , Danielsen Andreas A. , Rohde Christopher , Jefsen Oskar H. , Nielbo Kristoffer L. , Østergaard Søren D.
Published: July 2021

The COVID-19 pandemic has been shown to have major impact on global mental health. We show that the developments in COVID-19 pandemic-related psychopathology can be meaningfully monitored using machine learning methods providing invaluable insights to psychiatric services and of the management of the psychological consequences of the COVID-19 pandemic. The COVID-19 pandemic-related psychopathology among patients with mental illness was found to covary with the pandemic pressure, however, was less pronounced during the second wave compared to the first wave of the pandemic - possibly due to habituation.