Background: Sedation is an essential component of the transesophageal echocardiography (TEE) procedure for patient comfort. Utilization and the clinical implications of cardiologist-supervised (CARD-Sed) versus anesthesiologist-supervised sedation (ANES-Sed) are unknown. Methods: We reviewed non-operative TEE records from a single academic center over a five-year time period and identified CARD-Sed and ANES-Sed cases. We evaluated the impact of patient comorbidities, cardiac abnormalities on transthoracic echocardiogram (TTE), and the indication for TEE on sedation practice. We analyzed the use of CARD-Sed versus ANES-Sed in light of institutional guidelines, the consistency in the documentation of pre-procedural risk stratification, and the incidence of cardiopulmonary events including hypotension, hypoxia and hypercarbia. Results: A total of 914 patients underwent TEE, with 475 (52%) receiving CARD-Sed and 439 (48%) ANES-Sed. The presence of obstructive sleep apnea (p=0.008), a BMI greater than 45kg/m 2 (p<0.001), an EF of less than 30% (p<0.001) and pulmonary artery systolic pressure of more than 40 mm Hg (p=0.015) were all associated with the use of ANES-Sed. Of the 178 (19.5%) patients with at least one caution to non-anesthesiologist-supervised sedation by the institutional screening guideline, 65 (36.5%) underwent CARD-Sed. In the ANES-Sed group, where intraprocedural vital signs and medications were documented in all cases, hypotension (n = 91, 20.7%), vasoactive medication use (n=121, 27.6%), hypoxia (n= 35, 8.0%), and hypercarbia (n= 50, 11.4%) were noted. Conclusions: This single-center study revealed that 56% of the non-operative TEE utilized ANES-Sed over five years. Sedation-related hemodynamic changes and respiratory events were not infrequently encountered during ANES-Sed.

The exceptional conditions of the coast for the development of multiple human activities have led to a continuous migration of inhabitants, industries and services to the coastal areas. The reasons for such migration have evolved over time, being historically the commerce, the port activity and the agricultural settlements in the fertile deltas and alluvial plains the causes of such migration, while at present it is are tourism associated with leisure and the enjoyment of the coastline.

Objective: To present 29-year-old patient with neurosyphilitic changes characterized by multiple acute ischemic brain strokes along with significant narrowing of several large intracranial arteries. After treatment of patient with ceftriaxone for 14 days following benzathine benzylpenicillin weekly for additional three weeks, meningovascular changes regressed.

A proper benchmarking on the properties of HF and its dimer inside C60 using density functional theory (DFT) based approaches is presented. For this purpose, 10 different DFT functionals following Jacob’s Ladder have been chosen. Geometrical parameters, viz., bond length, bond angle, etc., and dipole moment have been computed. Two types of orientations, viz., L-shaped and anti-parallel of (HF)2 inside C60 are considered, the latter with an extremely short hydrogen bond. HF bond lengths are elongated upon encapsulation in comparison to its free state analogue. The calculated stability of HF@C60 is functional dependent whereas, (HF)2C60 is thermodynamically unstable for all the functionals. The kinetic stability of (HF)2@C60 is observed through ADMP simulation at 300K temperature. The red shift in HF stretching frequencies is noticed in all cases. NCI analysis exhibits a non-covalent type interaction between HF dimer and the C60 cage. The total interaction energy is found to be negative for HF@C60. EDA analysis showed a high value of repulsive ΔEpauli which makes the (HF)2@C60 system unstable except for the functional BP86-D3 of GGA family. Furthermore, QTAIM analysis is performed and confirmed the presence of (3, -1) bond critical point along the hydrogen bond region for L-shaped (HF)2C60.

The present first part about the eventual completeness of mathematics (called "Hilbert mathematics") is concentrated on the Gödel incompleteness (1931) statement: if it is an axiom rather than a theorem inferable from the axioms of (Peano) arithmetic, (ZFC) set theory, and propositional logic, this would pioneer the pathway to Hilbert mathematics. One of the main arguments that it is an axiom consists in the direct contradiction of the axiom of induction in arithmetic and the axiom of infinity in set theory. Thus, the pair of arithmetic and set are to be similar to Euclidean and non-Euclidean geometries distinguishably only by the Fifth postulate now, i.e. after replacing it and its negation correspondingly by the axiom of finiteness (induction) versus that of finiteness being idempotent negations to each other. Indeed, the axiom of choice, as far as it is equivalent to the well-ordering "theorem", transforms any set in a well-ordering either necessarily finite according to the axiom of induction or also optionally infinite according to the axiom of infinity. So, the Gödel incompleteness statement relies on the logical contradiction of the axiom of induction and the axiom of infinity in the final analysis. Nonetheless, both can be considered as two idempotent versions of the same axiom (analogically to the Fifth postulate) and then unified after logicism and its inherent intensionality since the opposition of finiteness and infinity can be only extensional (i.e., relevant to the elements of any set rather than to the set by itself or its characteristic property being a proposition). So, the pathway for interpreting the Gödel incompleteness statement as an axiom and the originating from that assumption for "Hilbert mathematics" accepting its negation is pioneered. A much wider context relevant to realizing the Gödel incompleteness statement as a metamathematical axiom is consistently built step by step. The horizon of Hilbert mathematics is the proper subject in the third part of the paper, and a reinterpretation of Gödel's papers (1930; 1931) as an apology of logicism as the only consistent foundations of mathematics is the topic of the next second part.

A document by Mao Li. Click on the document to view its contents.

Paraneoplastic syndrome is often not an obvious or common clinical presentation, but this report demonstrates that migratory arthropathies, may be the first presenting sign for non-small cell lung cancer (NSCLC). This study showcases an example of paraneoplastic syndrome, so other healthcare providers can be aware of early NSCLC manifestations.

Congenital dyserythropoietic anemias (CDA) is a heterogeneous class of anemia of varying degrees of ineffective erythropoiesis and secondary hemochromatosis. We reported a case of CDA and showed our approach to reaching a diagnosis, highlighting the importance of the typical morphological appearance of bone marrow erythroblasts to reach the diagnosis.

Background: Since the 2002 SCAR study, erythema multiforme(EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). Objectives: To describe EM reported in the FPDB and to compare the characteristics of the reports. Methods: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or one validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. Results: Among 182 selected reports, 140(77%) were analyzed. Of these, 67(48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36(49%) had a probable non-drug cause and 28(38%) were associated with only drugs with an onset time ≤4 days and/or ≥ 29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Conclusions: This study suggests that possible drug-induced EM is rare. Many reports describe “polymorphic” rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

The present study investigated the effect of solid-state fermentation (SSF) of cold-pressed (CP) and hexane-extracted (HE) canola meals with Aspergillus niger NRRL 334 and A. oryzae NRRL 5590 on the functionalities of protein products extracted from them. After SSF, proteins were recovered using alkaline extraction-isoelectric precipitation (AE-IP) or salt extraction-dialysis (SE). SSF of the two meal types reduced the protein content of the extracts produced by AE-IP. There were varied effects to solubility, foaming, and emulsifying properties as a result of SSF under the combined influence of functionality pH, strain, meal type, and protein extraction method. The protein isolate produced from CP meal using SE had increased solubility at pH 7 (from 51.8 to 90.7%) when the meal was fermented with A. oryzae. Both strains resulted in an over 2-fold increase in the emulsifying activity index (at pH 7) of AE-IP products from CP meal. For both protein extraction methods, the protein products from A. niger fermented HE meal had better foaming capacity (FC) at pH 7 than the controls (non-fermented), but reduced FC at pH 3. Overall, regardless of meal fermentation, the SE products were richer in protein and had higher oil holding capacity (OHC), whereas the water holding capacity (WHC) was higher for AE-IP isolates. SSF of the meals generally improved the O/WHC of the extracted proteins. The findings suggest that canola protein functionality could be effectively modulated by SSF with different microbial strains under various processing conditions to enhance their applicability in the food industry.

Aim: To determine the type, cause, severity and associated factors of DRPs in CKD patients, and then to assess the results of interventions by clinical pharmacists. Methods: A cross-sectional study was carried out to review all medication orders for hospitalized patients with CKD from April to September 2022. Pharmaceutical Care Network Europe classification (PCNE) V9.1 was used to classify the DRPs; Logistic regression models were used to estimate the factors of DRPs. Results: 176 patients with CKD stage 3-5 were included, and 249 DRPs were identified in 73.9% (130/176) of participants. The most common type of problem and cause respectively were “treatment effectiveness” (52.2%, 130/249) and “drug selection” (63.1%, 157/249). 84.7% (211/249) of the DRPs were rated at severity categories B to D (causing no or potential harm), whereas 15.3% (38/249) were rated as categories E to H (causing actual harm). Clinical pharmacists proposed 433 interventions, of which 89.4% (387/433) were entirely accepted and implemented, and solved 83.1% (207/249) DRPs. The probability of having at least one DRP was higher in patients treated with ten or more drugs (AOR 4.126, 95% CI 1.754-9.705, P=0.001), with CKD stages 5 (AOR 4.954, 95% CI 1.754-9.705, P=0.005), and with diabetes (AOR 4.224, 95% CI 1.889-9.445, P<0.001). Conclusions: DRPs are common in hospitalized CKD patients, and pharmacists play a significant role in optimizing medication therapy by identifying and resolving DRPs. The number of drugs, stage of CKD and diabetes are risk factors for DRPs, and we should pay attention to this specific group.

Necrobiosis Lipoidica (NL) is a rare granulomatous skin condition typically occurring in lower extremities. We report an atypical case of NL and we highlight the role of dermoscopy in the diagnostic approach.

During pregnancy, liver cirrhosis and portal hypertension may worsen significantly, placing an increased risk of serious morbidity and life-threatening events. With the use of a wide variety of diagnostic tools and improved treatment strategies, women with liver disease in pregnancies are being diagnosed with significantly improved obstetric outcomes

Succenturiate placenta can be associated with vasa previa, retained placenta, post-partum hemorrhage and infection. Prior knowledge of presence of succenturiate placenta can be helpful to take quick and rational decisions during the labor. We present a case of placenta succenturiate suspected at 34+3 weeks of gestation using findings from ultrasonography.

Cardiac etiologies of hemoptysis are less common. One such etiology includes mitral regurgitation. In patients with hemoptysis and unilateral consolidation, mitral valve regurgitation should be considered, and careful chest auscultation and cardiac assessment may assist in making an early diagnosis.

Abstract

During the era of genomics, many sequencing methods have been (and continue to be) developed. One family of methods that has recently gotten a lot of popularity is the reduced representation library method. Yet, there has not been much research into how to deal with combining reduced representation library data with other types, like (e.g.) whole genome sequencing data. Merging of different types of data can be difficult and lead to biases in downstream data analysis. This study attempts to identify the origin of some of these biases and propose strategies to minimize them, by using a dataset of six wolves that have been sequenced both with MobiSeq and standard whole genome sequencing. Taking the whole genome sequencing data as reference, we have taken a step-by-step approach to identify parameters that minimize the bias produced by MobiSeq. Our results show that missing data has a large effect on the data analysis. Therefore, we recommend that areas for variant calling should be limited to targeted regions of the reduced representation library method, and in some analysis the addition of requiring a minimum number of individuals can minimize the bias even more.

Left atrial field isolation with pulsed field ablation:

To the authorsʼ knowledge there is only one report in the literature, dealing with paramedullary plasmacytomas in horses as so-called “break out lesions”, originating from the bone marrow of a vertebra and invading the epidural space (Drew and Greatorex 1974). Our case report describes the clinical and patho-morphological findings of such a case. The affected 8-month-old warmblood weanling colt exhibited acute tetraparesis thus, a spinal cord lesion in the cervical column was suspected. Computed tomography revealed osteolytic lesions in C1 and a heterogeneous mass within the respective segment of the vertebral canal. By means of patho-morphological examination, with the aid of transmission electron microscopy, a plasmacytoma was identified, that had grown out of the bone marrow of C1 into the epidural space, locally compressing the spinal cord. In tetraparetic, young horses traumatic spine cord injuries, cervical vertebral malformations and infectious diseases of the central nervous system represent common differentials. However bone-dissolving tumours such as paramedullary plasmacytomas should be considered as a further possible cause in the presence of severe neurological deficits.

This paper is concerned with the spreading or vanishing of an epidemic disease which is characterized by a nonlocal diffusion SIR model with nonlocal incidence rate and double free boundaries. We prove that the disease will vanish if the basic reproduction number R 0 < 1 , or the initial area h 0 , the initial datum S 0 , and the expanding ability µ are sufficiently small even that R 0 > 1 , and the disease will spread to the whole area if R 0 > 1 , when h 0 is suitably large or h 0 is small but µ is large enough. Moreover, we also show that the long-time asymptotic limit of the solution when vanishing happens.

Background: The effect of cardiac resynchronization therapy (CRT) on the risk of ventricular arrhythmias is controversial. Several studies reported a decreased risk, but some studies reported a potential proarrhythmic effect of epicardial left ventricular pacing resolved upon discontinuation of biventricular pacing (BiVp). Case Summary: A 67-years old woman with a history of heart failure due to non-ischemic cardiomyopathy and left bundle brunch block was hospitalized for CRT device implantation. Unpredictably, as soon as the leads have been connected to the generator, electrical storm (ES) occurred with relapsing self-resolving polymorphic ventricular tachycardia (PVT) triggered by ventricular extra beats with short-long-short sequence. The ES was resolved without interrupting BiVp switching to unipolar left ventricular (LV) pacing. This allowed to keep CRT active with extreme clinical benefit for the patient and to demonstrate that the cause of the PVT was the anodic capture of bipolar LV stimulation. Reverse electrical remodeling was also demonstrated after 3 months of effective BiVp. Discussion: Proarrhythmic effect of CRT is a rare but significant complication of CRT, and it may compel to discontinue the BiVp. The reversal of the physiological transmural activation sequence of epicardial LV pacing and subsequent prolonging of corrected QT interval have been speculated as the most probable explanation, but our case highlights the possibility that the anodic capture may play a relevant role in PVT genesis.

In memoriam: Dr. Audrey E. EvansJohn M. Maris, MDDr. Audrey E. Evans, emeritus Professor of Pediatrics at the University of Pennsylvania and the first Chief of the Division of Oncology at the Children’s Hospital of Philadelphia (CHOP), died peacefully at her home on September 29, 2022, surrounded by loved ones at the age of 97. She will be remembered for her groundbreaking leadership in developing new treatments for children with cancer and for establishing the Philadelphia Ronald McDonald House as a home away from home for families whose children are being treated for serious illnesses. The original House in Philadelphia has served as the model for the now 375 Homes around the world today.Audrey E. Evans was born March 6, 1925, in York, England, the second of three children. Audrey developed a passion for horses and equestrian pursuits early in life that she carried with her well into her seventies. After receiving her medical training at the University of Edinburgh in Scotland, she came to the U.S. in the early 1950’s on a Fulbright scholarship. She trained with Dr. Sydney Farber and was on the frontline of the first successful treatments of human cancer with chemotherapy. During these early years in Boston, Baltimore and Chicago, Dr. Evans, formed her lifelong commitment to the problem of childhood cancer, and dedicated her career to not only improving cure rates, but also to do so with a focus on quality of life during and after treatment. She was a trailblazer and serves as a role model for several generations of pediatric oncologists. Her holistic view of how serious illness impacts not just the patient, but the entire family has influenced the approach to children with cancer of countless childhood cancer health care professionals. “A sick child is a sick family”, she would often say.Dr. Evans was recruited to the Children’s Hospital of Philadelphia (CHOP) in 1969 by future Surgeon General C. Everett Koop to be the first Director and Chief of the Division of Oncology. This was immediately followed by a dizzying array of seminal achievements. She was the first to develop a neuroblastoma staging system, and the fundamental aspects of the system remain in clinical use today. She was the first to describe, along with late husband Dr. Giulio (Dan) D’Angio, the amazing phenomena of spontaneous regression of widely disseminated neuroblastoma that she dubbed “4S disease” (S = special). Dr. Evans organized and chaired the inaugural Advances in Neuroblastoma Research (ANR) Meeting in a small conference room at CHOP in May of 1975. This meeting has grown into a major international conference attended by hundreds of physicians and scientists focused understanding neuroblastoma and improving patient outcomes.She oversaw enormous growth of the Division of Oncology at CHOP, and trained dozens of eventual leaders in the field. During this time, Dr. Evans was key to the formation of the first childhood cancer cooperative groups and led many of the early seminal studies. These efforts led to dramatically increased cure rates in a variety of childhood cancer, as well as establishing the infrastructure for all of the advancements made since. Her legacy in the field of pediatric oncology is unparalleled.Dr. Evans was one of the first to recognize the importance of the nursing, psychology, and social work disciplines to the care of children with cancer. She recruited individuals in these fields well before her peers, and current rich collaborative programs with these disciplines in oncology are due to Dr. Evans’ pioneering efforts.Faced with the problems associated with a growing cancer program at CHOP, namely, how to care for the child and their families, in 1974 Dr. Evans co-founded with Philadelphia Eagles General Manager Jimmy Murray the original Ronald McDonald House on Chestnut Street in Philadelphia, a short walk from CHOP. There are now McDonald Houses across the globe, all enabled by Dr. Evans’ vision. Dr. Evans was also instrumental to the start of the Ronald McDonald Camps for children with cancer and survivors, establishing the program in 1987.Dr. Evans has received essentially every honor possible in the field of pediatric oncology. These include, but are not limited to, the Janeway Award, the American Society of Pediatric Hematology/Oncology Distinguished Career Award, an award from the American Cancer Society, the Spectrum Award of the American Red Cross, the Alpha Delta Kappa International Woman of the Year Award, the Osler Award from the University of Pennsylvania, the Lifetime Achievement Award from the International Society of Paediatric Oncology (with her husband), and most recently, an honorary Fellowship of the Royal College of Physicians of Edinburgh, her Alma Mater.Audrey married Dan D’Angio just before her 80thbirthday in a humble ceremony followed by a cup of tea and then return to work at CHOP. A true Renaissance woman, Audrey will be remembered not only for her groundbreaking work in pediatric oncology, but also for passion for dressage, scuba diving, and her annual early spring trips to Scotland to assist in birthing lambs. After retiring at in 2009, she focused on establishing and nourishing the St. James School for at-risk children in North Philadelphia with Dan’s able assistance. Audrey and Dan spent many wonderful years together on Rittenhouse Square in Philadelphia until his death in their home on September 14, 2018. She died peacefully in the same place with the singular goal of joining him again.

Purpose : To determine whether extent of surgical resection of the primary tumour correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. Methods : Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001-2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumour based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem-cell transplant (SCT). Results : One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete vs. incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p=0.008 and p=0.002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT and surgical resection, only complete resection was associated with statistically significant improved 3 yr EFS and OS, HR=0.48 (0.29-0.81; p=0.006) and HR=0.42 (0.24-0.73; p=0.002). Conclusions : In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.

Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective, but needs to be improved. A total of 115 patients (60 males; median age of 5.77 years and median follow-up time of 45 months) were enrolled in this historical control study. The complete response (CR) rates in the eltrombopag group were 30.3% at 3 months, 50.0% at 6 months, conpared to 8.2% at 3 months, 10.2% at 6 months in the control group. There were significant differences between the two groups at 3 months and 6 months after IST. The overall response rates in the two groups showed no significant differences during the study. There were significant differences in the times separated from granulocyte colony stimulating factor (G-CSF) G-CSF, red blood cell transfusion and Platelet transfusion between the two groups. Overall survival rates were 97.0% in the eltrombopag group and 96.0% in the control group (P=0.998). In the eltrombopag group 10.2% cases relapsed compared to 4.1% in the control group (P=0.703). No case progressed to myelodysplastic syndrome or myeloid leukemia in the eltrombopag group; one patient (2.0%) progressed to myelodysplastic syndrome in the control group. Totally 11 patients (16.7%) showed myeloid gene mutations in the eltrombopag group. Event-free survival (EFS) was 66.6% in the eltrombopag group and 57.1% in the control group. There were no significant differences in EFS between the two groups (P=0.967). In the eltrombopag group the common adverse reactions were transient and reversible hyperbilirubinemia, elevated liver enzymesand hyperuricemia.