When Thetis dipped her son Achilles into the River Styx to make him immortal, she held him by the Heel, which was not submerged, and thus created a weak spot that proved deadly for Achilles. Millennia later, Achilles Heel is part of today’s lexicon meaning an area of weakness or a vulnerable spot that causes failure. Also implied is that an Achilles Heel is often missed, forgotten or underappreciated, until it is under attack, and then failure is fatal. Paris killed Achilles with an arrow ‘guided by the Gods’. At the International Congress of the Immunology of Diabetes Society, 2018, five leading experts were asked to present the case for a particular cell/element that could represent the Achilles Heel of T1D. Their arguments are summarized here, to make this case.

In recent years Next-Generation Sequencing (NGS) based methods to detect mutations in biotherapeutic transgene products have become a key quality step deployed during the development of manufacturing cell line clones. Previously we reported on a higher throughput, rapid mutation detection method based on amplicon sequencing (targeting transgene RNA) and detailed its implementation to facilitate cell line clone selection. By gaining experience with our assay in a diverse set of cell line development programs, we improved the computational analysis as well as experimental protocols. Here we report on these improvements as well as on a comprehensive benchmarking of our assay. We evaluated assay performance by mixing amplicon samples of a verified mutated antibody clone with a non-mutated antibody clone to generate spike-in mutations from ~60% down to ~0.3% frequencies. We subsequently tested the effect of 16 different sample and NGS library preparation protocols on the assay’s ability to quantify mutations and on the occurrence of false-positive background error mutations (artifacts). Our evaluation confirmed assay robustness, established a high confidence limit of detection of ~0.6%, and identified protocols that reduce error levels thereby significantly reducing a source of false positives that bottlenecked the identification of low-level true mutations.

Aim: To show if lower urinary tract symptoms (LUTS) could be symptoms of COVID-19 with validated questionnaires. Methods: The 96 COVID-19 patients who were hospitalized at a tertiary center were collected retrospectively. After the exclusion criteria, 46 patients were consisted as the study population. The male and female patients then fill formed the International Prostate Symptom Score and Urinary Symptom Profile respectively. All patients responded to these questions for the three period. Results: 27 female (58.6 %) and 19 male (41.4 %) COVID-19 patients answered the questions In the male patients, while there were no statistically significant differences in the total IPSS, the voiding IPSS score, and quality of life between the three periods (p=0.148; p=0.933, p=0.079, respectively), the storage IPSS scores had a significant difference between the three periods (p=0.05). In the female patients, low stream scores, were similar between the three periods (p=0.368). The scores of stress incontinence and an overactive bladder had a significant difference between the three periods (p=0.05 and p=0.05). Conclusion: LUTS, especially storage symptoms, might be one of the initial symptoms of COVID-19 and the clinicians should evaluate LUTS with other known symptoms of the virus when a patient is suspected of having COVID-19.

ABSTRACT Aim: To investigate the effect of COVID-19 on sexual dysfunction in women. Materials and Methods: The women diagnosed with COVID-19 and hospitalized at a tertiary hospital were included. They completed the Introductory Data Form, the Female Sexual Function Index-(FSFI), and the Short Form-36 Quality of Life Scale (SF-36). Results: 15 women between the ages of 19-49 who completed the treatment protocol, discharged at least 14 days before, and who had not been diagnosed as sexual dysfunction sexually active earlier were included to the study. It was detected that weekly sexual intercourse before and after COVID-19 significantly differed (p=0.047). The frequency of relationships decreased statistically after COVID-19. The mean value of the FSFI satisfaction score differs from COVID-19 before and after diagnosis (p=0.012). The mean satisfaction score before COVID-19 was 3.47, and after COVID-19 was 2.93. The score of the subgroups of FSFI did not differ from COVID-19 before and after diagnosis (p>0.050). The median value of SF-36 pain differs from COVID-19 before and after diagnosis (p=0.008). Conclusion: it was concluded that the frequency of sexual intercourse, sexual satisfaction in women decreased after COVID-19 disease, and the quality of life scores did not change in a statistically significant way.

Childhood cancer survivors are at increased risk for treatment-related late effects; data are lacking on how COVID-19 infection impacts this cohort. We assessed COVID-19-related symptoms; SARS-CoV-2 IgG seroprevalence; and rate of COVID-19-related hospitalization among 321 asymptomatic survivors of childhood cancer or transplantation seen for routine long-term follow-up between May-September 2020 in a New York City tertiary cancer center. While 11% (n=35) reported possible COVID-19-related symptoms, 7.8% (n=20) of those tested had positive SARS-CoV-2 IgG, and only 1 patient (0.3%) required COVID-19 related hospitalization. This report suggests that childhood cancer survivors are at low risk for COVID-19 complications.

Background: This retrospective study harnessed an institutional cancer registry to construct a childhood cancer survivorship cohort, integrate electronic health record (EHR) and geospatial data to risk stratify patients for serious adverse health outcomes, analyze follow-up care patterns, and determine factors associated with suboptimal follow-up care. Procedure: The survivorship cohort included patients ≤18 years of age with a diagnosis of a malignancy reported to the institutional cancer registry between January 1, 1994 and November 30, 2012. ICD-O-3 coding and treatment exposures facilitated risk stratification of survivors. All follow-up visits were extracted from the EHR through linkage to the cancer registry based on medical record number (MRN). Results: Eight-hundred-and-sixty-five survivors were included in the final analytic cohort, of whom 191, 496, and 158 were considered low, intermediate, and high risk survivors, respectively. Two-hundred-and-eight-two survivors (32.6%) were not seen in any oncology-related subspecialty clinic at Duke five to seven years after initial diagnosis. Factors associated with a clinic visit included younger age (p=0.008), acute lymphoblastic leukemia (ALL) as the primary diagnosis (p<0.001), race/ethnicity (p=0.010), risk strata (p=0.001), distance to treatment center (p<0.0001), and lower ADI (p=0.011). Multivariable logistic modeling with adjustment for diagnosis of ALL, gender, age at diagnosis, and race/ethnicity attenuated the association between follow-up care and risk strata (p=0.17) Conclusions: Nearly a third of survivors received suboptimal follow-up care. This study provides a reproducible model to integrate cancer registry and EHR data to construct risk-stratified survivorship cohorts to assess follow-up care.

Texas horned lizards (Phrynosoma cornutum) have a number of ways to avoid predation, including camouflage, sharp cranial horns, flattening of the body, and the ability to squirt blood from the eyes. These characteristics and their relatively low survival rates in the wild suggests these lizards are under high predation pressure. These lizards have been declining in much of their eastern range due to increased urbanization, agriculture, and loss of prey species. However, they can be still be found in some small south Texas towns where they can reach densities that are much higher (~50 lizards/ha) than in natural areas (~4-10 lizards/ha). We hypothesized that one reason for the high densities observed in these towns may be due to reduced predation pressure. We used model Texas horned lizards to test whether predation levels were lower in two south Texas towns than on a nearby ranch. We constructed models from urethane foam, a material that is ideal for preserving marks left behind by predators. Models (n = 126) and control pieces of foam (n = 21) were left in the field for 9 days in each location in early and late summer and subsequent predation marks were categorized by predator taxa. We observed significantly more predation attempts on the models than on controls and significantly fewer attempts in town (n = 1) compared to the ranch (n = 60). On the ranch, avian predation attempts appear to be common especially when the models did not match the color of the soil. Our results suggest that human modified environments that have suitable habitat and food resources may provide a refuge for some prey species like horned lizards from predators.

Mini-commentary on BJOG-20-1651.R1: Early and late pregnancy loss in women with polycystic ovary syndrome undergoing IVF/ICSI treatment: a retrospective cohort analysis of 21,820 pregnancies

This article presents an investigation on free convection flow and heat and mass transfer of fractional nanofluids formed by different base fluids with different shaped copper nanoparticles past an infinite vertical plate with radiation effect. The model which describes the system involving partial differential equations is converted into model of fractional nanofluids using Caputo time derivatives, which explains the impact of memory on behavior of nanofluids and are solved by employing technique of Laplace transform. The different base fluids - water $(H_2 O)$, $SA$:sodium alginate $(C_{6}H_{9}Na O_{7})$ and $EG$:ethylene glycol $(C_{2}H_{6}O_{2})$ and various shapes of nanoparticles - blade, brick, platelet and cylinder are considered for the study. The exact solutions are obtained for the temperature, concentration and velocity distributions and the respective Nusselt number, Sherwood number and skin-friction coefficient. The influence of non-dimensional parameters like fractional parameter, Schmidt number, radiation parameter, nanoparticle volume fraction, etc., which provides physical interpretations of temperature, concentration and velocity fields, Nusselt number, Sherwood number and skin-friction are discussed in detail with the aid of graphical representations. From the results it is found that fractional nanofluids formed by water based blade shaped nanoparticle exhibits more velocity and temperature distributions. Also, strengthen of fluid flow, temperature and concentration of nanofluids are inversely correlate with the order of fractional derivatives.

Hurricanes are extreme phenomena that affect the coasts of Mexico every year. The economic and biodiversity losses caused by these extreme events are extensive. However, little is known about the effects that these severe weather incidents have on Mexico’s forest conservation and protected areas. A hydrological characterization and regionalization of the storms caused by the rain fields generated by all the hurricanes that touched the Mexican coast from 1966 to 2017 were carried out. Adimensional Huff Curves are proposed to get precipitation hyetograms from which the erosion factor of a storm is obtained; using the Universal Soil Loss Method (USLE). The results made it possible to get the typical precipitation hyetograms in the forests and protected areas, before, during, and after the impact of a hurricane. The proposed hydrological regionalization made it possible to estimate the rainfall intensity in 30 minutes to characterize the start of rain erosion. The method proposed in this research was applied in the 177 Natural Protected Areas (25628239 ha), as well as in the 370 voluntarily designated areas for Conservation (399643 ha), in Mexico. It is concluded that, with the regionalization and the proposed equations, it is possible to get typical hurricane precipitation hyetograms, which would allow us to detail the forest management plans in forests, ecological reserves, and protected areas of Mexico.

Background: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. Methods: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients <18 years and initiating omalizumab between 2006-2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared to the baseline period. Results: Of the 484 patients included, 101 (20.9%) reached six years of treatment. The mean±standard deviation number of exacerbations decreased during the first year of treatment (7.9±6.6 to 1.1±2.0, p<0.001) and remained likewise for up to six years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. Conclusion: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long-term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Here we report the seven-year long-term survival after Aspergillus fumigatus mediastinitis after heart transplantation, an uncommonly described condition. A 66-year-old male developed infection with A. fumigatus covering the entire thoracic cavity with a fungal turf after orthotopic heart transplantation. Repeated surgical removal of infectious and necrotic tissue together with innovative topical treatment using voriconazole and chlorhexidine combined with systemic antifungal treatment lead to control of infection. Definitive wound closure was achieved by standard sternal refixation and latissimus dorsi muscle flap plasty. Survival after A. fumigatus mediastinitis after heart transplantation was achieved with sequential debridement in combination with topical application of antifungal agents.

Objectives: Epistaxis is the second most common referral to the Ear nose and throat (ENT) department. Frailty, a marker for biological vulnerability, has been shown to increase the risk of haemorrhage, but its impact in epistaxis patients is unknown. We aim to establish the impact of Clinical Frailty score, as well as other established risk factors for epistaxis, on the likelihood of admission in patients presenting to secondary care with epistaxis. Design: Retrospective cohort study Setting: University hospital Otolaryngology department Participants: Adult patients presenting to hospital with epistaxis between March 2019 and March 2020. Main outcome measures: We compare the clinical frailty score of patients admitted with epistaxis to those patients seen and treated same day. Results: 299 epistaxis presentations were identified, of which 122 (30.8%) required admission for further management. Clinical frailty score of ≥4 had an increased odds for admission (OR 3.15 (95% CI:1.94 – 5.16), p<0.001). In the majority of presentations (66.2%), patients were taking either an antiplatelet, anticoagulant or a combination of them. Of these presentations, the use of an anticoagulant (OR: 2.00 (95% CI: 1.20-1.92), p:0.10) and dual antiplatelet (OR: 2.82 (95% CI: 1.02-7.86), p:0.10, p:0.07) demonstrated increased odds of admission. Conclusions: We have shown that frailty increases the risk of admission in adult patients presenting with epistaxis. Frailty is becoming an increasingly apparent independent cause for haemorrhage in the elderly population. Careful consideration of bleeding risks, particularly in frail patients, needs addressing due to the morbidity associated with epistaxis.

Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells and epithelial cells. During recent years, clinical and experimental studies on human mast cells as well as experiments using animal models have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity and reactivity. We also highlight the development in our understanding of mast cell driven-diseases and discuss the development of novel strategies to treat such conditions.

Mini-commentary on BJOG-20-1459.R1: Caesarean birth and risk of subsequent preterm birth: retrospective cohort studyDeclarative title to be addedBradley de VriesSchool of Public HealthUniversity of SydneySydneyNew South WalesAustraliaWorldwide, preterm birth occurs in 11% of pregnancies and is the leading cause of childhood mortality. Complications from preterm birth are the most common cause of neonatal death in the United Kingdom, yet the incidence of preterm birth is not falling.In this issue of BJOG, Williams et al (BJOG xxxx) report on an observational study which identifies previous second stage caesarean birth as a risk factor for spontaneous preterm birth, confirming the results of other observational cohorts. Among women with one previous term birth, the adjusted odds ratio was 2.1 (95% confidence interval [CI] 1.3 to 3.1) for preterm birth before 37 weeks gestational age and 7.5 (95% CI 3.4 to 15) for preterm birth before 34 weeks, for previous second stage caesarean birth compared with previous vaginal birth. They adjusted for confounders not addressed in other studies including interpregnancy interval and maternal deprivation index, strengthening the existing evidence. The association is plausible because the cervix and lower uterine segment are anatomically merged in the second stage of labour and inadvertent cervical incision might damage the integrity of the cervix. The association was at least as strong as that described for previous excisional surgery for cervical dysplasia. Current National Institute of Clinical Excellence Guidelines recommend considering prophylactic cervical cerclage for an ultrasound-measured cervical length < 25mm if there is a history of cervical trauma. Given the plausibility and emerging epidemiological evidence, it would seem prudent to offer the same screening and treatment when there is a history of second stage caesarean birth.The observed association is relevant in other ways. Counselling about instrumental versus caesarean birth may be influenced by knowledge of future risks. Additionally, surgeons may need to be aware of the potential importance of avoiding inadvertent cervical incision, while still avoiding upper segment incision and its attendant risk of future intrapartum uterine rupture.The study by Williams et al is well designed, yet there remains potential for confounding not adjusted for in the analysis. Further, missing data for body mass index (1.6%) and cigarette smoking (13%) were classified as unknown and not imputed which can also cause bias. As there are only a handful of observational studies, it would be sensible to confirm the association, and explore potential causative mechanisms (e.g., by monitoring cervical length in subsequent pregnancies).Clinical prediction models for spontaneous preterm labour in asymptomatic women have been developed but need improvement before incorporation into clinical practice. Addition of new risk factors such as second stage caesarean birth and better understanding of the causes of preterm birth could improve these models and ultimately improve outcomes through offering prophylaxis with cervical cerclage, vaginal progesterone, or pessary for women at high risk.Given the massive personal, clinical, and economic burden imposed by preterm birth, the plausibility of the association, and the growing evidence from observational studies, I believe cervical surveillance warranted, with a view to offering prophylactic measures when there is a history of second stage caesarean birth.No disclosures: A completed disclosure of interest form is available to view online as supporting information.

The care of patients with vascular anomalies is quickly becoming a complex field requiring high quality, coordinated multidisciplinary care. In this article, we review the history of multidisciplinary care in this field, discuss the benefits of this model of care, and outline some of the essential components and structure of a successful vascular anomalies team. We provide an overview of two example programs and a roadmap for other centers to develop their own multidisciplinary vascular anomalies teams.

A document by Denise Adams. Click on the document to view its contents.

Background Symptom-focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy. Objectives To evaluate the use of rhythm control and rate control strategy. Second, to identify predictors of the use of amiodarone in patients with rhythm control and of the use of rhythm control strategy in patients with paroxysmal AF in the Balkans. Methods Prospective enrolment of consecutive patients from 7 Balkan countries to the BALKAN-AF survey was performed. Results Of 2,712 enrolled patients, 2,522 (93.0%) with complete data were included: 1,622 (64.3%) patients were assigned to rate control strategy and 900 (35.7%) to rhythm control. Patients with rhythm control were younger, more often hospitalized for AF and with less comorbidities (all p <0.05) than those with rate control. Symptom score [European Heart Rhythm Association (EHRA)] was not an independent predictor of a rhythm control strategy [odds ratio (OR) 0.99, 95% confidence interval (CI) 0.90-1.10, p = 0.945]. The most commonly chosen antiarrhythmic agents were amiodarone (49.7%), followed by propafenone (24.3%). Conclusion More than one third of patients in BALKAN-AF survey received a rhythm control strategy, and these patients tended to be younger with less comorbidities than those managed with rate control. EHRA symptom score is not significantly associated with rhythm control strategy. The most commonly used antiarrhythmic agents were amiodarone, followed by propafenone.