4′-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication

Preparing antiviral defenses Antiviral drugs are an important tool in the battle against COVID-19. Both remdesivir and molnupiravir, which target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase, were first developed against other RNA viruses. This highlights the importance of broad-spectrum antivirals that can be rapidly deployed against related emerging pathogens. Sourimant et al . used respiratory syncytial virus (RSV) as a primary indication in identifying further drugs that target the polymerase enzyme of RNA viruses. The authors explored derivatives of molnupiravir and identified 4′ fluorouridine (EIDD-2749) as an inhibitor of the polymerase of RSV and SARS-CoV-2. This drug can be delivered orally and was effective against RSV in mice and SARS-CoV-2 in ferrets. —VV

The Discrepancy between Gross Features and Chemical Compositions in Gallbladder Stone: A Descriptive Single Center Study in the United Arab Emirates

Background and Study Aim: Gallbladder stone (GBS) is a common gastrointestinal disease that is the primary indication for cholecystectomy. The present study was conducted to describe the chemical composition of gallstones in a tertiary referral hospital in the United Arab Emirates. Materials and Methods: Patients diagnosed with GBS and who underwent cholecystectomy due to symptomatic GBS and cholecystitis in Sheikh Khalifa Specialty Hospital were enrolled in this study. After cholecystectomy, all stone specimens were classified according to their gross findings into 4 groups, namely black pigmented stones (BLPS), brown pigmented stones (BRPS), mixed cholesterol stones, and cholesterol stones (CLS). Quantitative analysis using Fourier transform infrared spectroscopy was then performed to define the stones’ chemical constituents. They were reclassified into two groups as CLS (cholesterol ≥ 60%) and pigmented stones (PGS, cholesterol ≤ 59%) based on gallstone composition analysis. Results: A total of 237 stones were divided into four groups based on their gross findings; cholesterol stones (32.0%), mixed cholesterol (29.2%), black pigmented (26.4%), and brown pigmented (12.3%). After chemical composition analysis, they were resorted into the two following groups according to their cholesterol proportions: pigmented (28.3%) and cholesterol (71.7%). There were significant statistical mean age differences between the pigmented and cholesterol stone groups (58.5±19.8 vs. 34.4±11.0, p < 0.01). Conclusion: This descriptive study showed the hospital-based clinical incidence of GBS and suggested that there might be a discrepancy in stone classification based on gross findings and chemical compositions. Moreover, pigmented stones are more likely to be present in older patients than cholesterol stones.

Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention

Cholestatic jaundice is a common presenting feature of hepatobiliary and/or metabolic dysfunction in the newborn and young infant. Timely detection of cholestasis, followed by rapid step-wise evaluation to determine the etiology, is crucial to identify those causes that are amenable to medical or surgical intervention and to optimize outcomes for all infants. In the past 2 decades, genetic etiologies have been elucidated for many cholestatic diseases, and next-generation sequencing, whole-exome sequencing, and whole-genome sequencing now allow for relatively rapid and cost-effective diagnosis of conditions not previously identifiable via standard blood tests and/or liver biopsy. Advances have also been made in our understanding of risk factors for parenteral nutrition–associated cholestasis/liver disease. New lipid emulsion formulations, coupled with preventive measures to decrease central line–associated bloodstream infections, have resulted in lower rates of cholestasis and liver disease in infants and children receiving long-term parental nutrition. Unfortunately, little progress has been made in determining the exact cause of biliary atresia. The median age at the time of the hepatoportoenterostomy procedure is still greater than 60 days; consequently, biliary atresia remains the primary indication for pediatric liver transplantation. Several emerging therapies may reduce the bile acid load to the liver and improve outcomes in some neonatal cholestatic disorders. The goal of this article is to review the etiologies, diagnostic algorithms, and current and future management strategies for infants with cholestasis.

Meckel’s Diverticulum Diagnosed by Balloon-Assisted Enteroscopy: A Multicenter Report from the Taiwan Association for the Study of Small Intestinal Diseases (TASSID)

Background and Aims. Patients with Meckel’s diverticulum (MD) are difficult to preoperatively diagnose because of its endoscopic inaccessibility. Balloon-assisted enteroscopy (BAE) allows endoscopic access to the entire small intestine. The aim of the current study was to investigate patients with MD diagnosed by BAE in Taiwan. Methods. We conducted a retrospective, multicenter study of patients with MD who were diagnosed by BAE in Taiwan. The clinical characteristics, endoscopic features, histopathological findings, treatment methods, and outcomes were analyzed. Results. A total of 55 patients with MD were enrolled (46 males and 9 females). The mean age at diagnosis was 34.1 years. Overt gastrointestinal bleeding (87.3%) was the primary indication for BAE, followed by abdominal pain (9.1%), suspected small bowel tumor (1.8%), and Crohn’s disease follow-up (1.8%). The mean distance between the ileocecal valve and MD was 71.6 cm (regarding diagnostic yields: BAE—100%, capsule endoscopy—40%, Meckel’s scan—35.7%, computed tomography—14.6%, small bowel series—12.5%, and angiography—11.1%; regarding endoscopic features of MD: a large ostium—89.1%, a small ostium—7.3%, and a polypoid mass—3.6%). Surgical treatment was performed in 76.4% patients, and conservative treatment was performed in 23.6% patients. The mean length of MD in 42 patients who underwent surgical resection was 5.2 cm (in 43 patients of MD with available histopathology: heterotopic gastric tissue, 42.4%, heterotopic gastric and pancreatic tissues, 7%; heterotopic pancreatic tissue, 4.7%; heterotopic colonic tissue, 2.3%; and a neuroendocrine tumor, 2.3%). Conclusions. The current study showed BAE is a very useful modality for detecting MD compared with other conventional modalities.

Substantial Variation in Peripherally Inserted Central Catheter Use and Outcomes in Patients with Hematologic Malignancies: A Multi-Center Study

Background: Use of peripherally inserted central catheters (PICCs) has grown rapidly in patients with hematologic malignancies. Studies demonstrating the safety of PICCs in hematologic malignancies, however, are largely single-center, retrospective designs focused on the outpatient setting. Little is known about inpatient PICC use in patients with hematologic malignancies and how such use varies across hospitals. Methods: Data was prospectively collected between November 2013 and December 2019 from a cohort of patients admitted at one of 42 Michigan hospitals participating in the Michigan Hospital Medicine Safety Consortium (HMS). Patients had a diagnosis of a hematologic malignancy and had a PICC placed during their hospital stay. Adult medical patients admitted to a general ward or intensive care unit were eligible for data collection and data were collected from the medical record using a standardized template. The indications for PICC placement, catheter characteristics, and associated complications from 17 hospitals with more than 25 discrete patients with hematologic malignancy were included in a comparative analysis. Major complications were defined as central line associated bloodstream infection (CLABSI), catheter occlusion, and venous thromboembolism (VTE). Differences across hospitals were tested using the Kruskal-Wallis test for continuous variables and Pearson chi-square test for categorical variables. Results: A total of 2092 PICCs placed in 1798 patients were included in the analysis with a median (IQR) dwell time of 15 (6-30) days. Most patients were male (n=1242, 59.4%), white (n=1720, 82.2%), and 50 to 69 years old (n=950, 45.4%). Patients were primarily admitted to large hospitals (≥375 beds: n=1429, 68.8%) that were teaching centers (n=1600, 76.5%) in metropolitan locations (n=2000, 95.6%). Leukemia (n=752, 36.0%) and non-Hodgkin's lymphoma (n=409, 19.6%) were the most represented malignancies. The most common primary indication for PICC placement was administration of chemotherapy (n=1180, 56.4%). The majority of PICCs were double lumen (n=1457, 69.6%), most often placed by vascular access nurses (n=1520, 72.7%). A concurrent central venous catheter was present at the time of PICC placement in 12.2% (n=264) of patients. A major complication event occurred in over 1 in 4 PICCs placed (n=562, 26.9%). Catheter occlusion occurred in 17.8% (n=372), CLABSI in 8.2% (n=171), and VTE in 3.8% (n=80) of PICCs respectively. There was wide variation in PICC indications, characteristics, and outcomes across hospitals. Placement of PICCs for chemotherapy varied from 33.3% to 85.3% (p&lt;0.001). Similarly, there was a wide range of placement for antibiotics (2.8% to 32.4%, p&lt;0.001), transfusion of blood products (0.0% to 9.7%, p&lt;0.001), medications requiring central access (0% to 26.7%, p&lt;0.001), difficult access and blood draws (1.8% to 33.3%, p&lt;0.001), and administration of total parenteral nutrition (0.0% to 14.3%, p=0.002). There was significant variation in the number of lumens used: single (5.6% to 37.9%, p&lt;0.001), double (51.9% to 93.0%, p&lt;0.001), or triple (0.0% to 30.8%, p&lt;0.001). The incidence of major complications spanned from 9.7% to 40.8% (p=0.001). Rate of catheter occlusion had the widest range (0.0% to 36.7%, p&lt;0.001). The differences between rates of VTE (0.0% to 8.7%, p=0.29) and CLABSI (1.4% to 15.9%, p&lt; 0.20) were not statistically significant. Patient mortality ranged from 2.8% to 19.4% (p&lt;0.001). Conclusion: Appropriate venous access is critical to the care of patients with hematologic malignancy. This study demonstrates wide variation in the practice patterns and outcomes for PICCs in patients with hematologic malignancies across hospitals in Michigan. Further work is necessary to further understand and improve decision making around choosing vascular access in this vulnerable population. Figure 1 Figure 1. Disclosures Zhang: SIMR, Inc: Ended employment in the past 24 months, Research Funding; AmerisourceBergen: Current Employment. Sood: Bayer: Consultancy.

"I'm Ready for You. Why Won't You Come, Baby?" A Narrative Study of Induction of Labour for Prolonged Pregnancy

<p>The voice of women's experience of prolonged pregnancy and induction of labour is largely absent in the literature. This research relays and reflects upon the stories of four women who were induced because their pregnancies were overdue. The date a woman's baby is due has assumed huge significance. However our methods for dating a pregnancy remain imprecise. Despite this, a very precise timing is recommended by some practitioners as to when to induce, since increasing length of pregnancy increases level of risk of morbidity or mortality to some babies. For the women awaiting the onset of labour and their families, the undercurrents, which affect the milieu as the days pass, include powerful dichotomies. For example the best available research makes a clear recommendation to intervene but reinforces the woman's choice of management, suggesting that it is acceptable to choose to wait. Women experience emotional vulnerability due to apprehension both about continuing to wait, and about having the increasing likelihood of an induced labour. This is a decision that comes closer and closer, yet may not be necessary - a tense 'race' of sorts is in progress. Women experience mounting physical and social pressures, and a generalised, escalating frustration. Some of the common assumptions made about what it is like for women are that it is a struggle to accept the concept of the unreliability of the due date, to parry well meaning but unhelpful comments and the associated pressure, and to remain confident and phlegmatic when there is an alternative to waiting. An increasing number of women go on to be induced. The primary indication cited is 'prolonged pregnancy'. I have employed a narrative approach, using a feminist process and story telling, to convey the experience of being overdue and being induced, together with commentary informed by the literature and reflection on practice. Here women are speaking to women. The vivid detail and openness of the stories engrave messages to caregivers regarding women's needs for support while waiting, and for more information. The stories repeat messages documented in research carried out 25 years ago. Women require best available information, wish to be included in decision making, and should be encouraged to question their midwives and other caregivers on all aspects of pregnancy and proffered interventions.</p>

"I'm Ready for You. Why Won't You Come, Baby?" A Narrative Study of Induction of Labour for Prolonged Pregnancy

<p>The voice of women's experience of prolonged pregnancy and induction of labour is largely absent in the literature. This research relays and reflects upon the stories of four women who were induced because their pregnancies were overdue. The date a woman's baby is due has assumed huge significance. However our methods for dating a pregnancy remain imprecise. Despite this, a very precise timing is recommended by some practitioners as to when to induce, since increasing length of pregnancy increases level of risk of morbidity or mortality to some babies. For the women awaiting the onset of labour and their families, the undercurrents, which affect the milieu as the days pass, include powerful dichotomies. For example the best available research makes a clear recommendation to intervene but reinforces the woman's choice of management, suggesting that it is acceptable to choose to wait. Women experience emotional vulnerability due to apprehension both about continuing to wait, and about having the increasing likelihood of an induced labour. This is a decision that comes closer and closer, yet may not be necessary - a tense 'race' of sorts is in progress. Women experience mounting physical and social pressures, and a generalised, escalating frustration. Some of the common assumptions made about what it is like for women are that it is a struggle to accept the concept of the unreliability of the due date, to parry well meaning but unhelpful comments and the associated pressure, and to remain confident and phlegmatic when there is an alternative to waiting. An increasing number of women go on to be induced. The primary indication cited is 'prolonged pregnancy'. I have employed a narrative approach, using a feminist process and story telling, to convey the experience of being overdue and being induced, together with commentary informed by the literature and reflection on practice. Here women are speaking to women. The vivid detail and openness of the stories engrave messages to caregivers regarding women's needs for support while waiting, and for more information. The stories repeat messages documented in research carried out 25 years ago. Women require best available information, wish to be included in decision making, and should be encouraged to question their midwives and other caregivers on all aspects of pregnancy and proffered interventions.</p>

Pediatric Gastrointestinal Endoscopy: Diagnostic Yield and Appropriateness of Referral Based on Clinical Presentation: A Pilot Study

Objectives: There is a lack of evidence-based consensus for the utility of gastrointestinal endoscopy (GIE) in an array of frequently occurring symptoms in children. We aimed to assess the diagnostic yield of endoscopy in an effort to aid clinical decision making.Methods: Retrospective analysis included patients ≤18 years who underwent GIE during one calendar year at Shaare Zedek Medical Center. We excluded children referred for predefined obvious indications for GIE, planned follow-up procedures, and therapeutic endoscopy. Clinician-assigned indication for endoscopy as well as endoscopic and histologic findings were recorded. Diagnostic yield of GIE was determined according to referral indication.Results: There were 794 endoscopies performed of which 329 were included in the analysis (mean age 9.3 ± 5.0 years, 51% female). No significant complications of GIE were recorded. Six major referral indications were identified among which abdominal pain was the most frequent 88/329 (26%) of whom 32/88 (36%) had a significant diagnostic finding. Among the other major indications, diagnostic findings were found in 36/85 (43%) children with primary indication of chronic diarrhea, 14/33 (42%) failure to thrive, 15/32 (46%) short stature, 30/56 (54%) iron deficiency, and 20/48 (42%) weight loss.Conclusions: Pediatric GIE is a safe procedure with diverse clinical indications. The diagnostic yield of endoscopy is variable, depending on the referral indication. These data can assist formulating judicious referral practices.

Balloon Aortic Valvuloplasty for Severe Aortic Stenosis as Rescue or Bridge Therapy

The study aimed to assess procedural complications, patient flow and clinical outcomes after balloon aortic valvuloplasty (BAV) as rescue or bridge therapy, based on data from our registry. A total of 382 BAVs in 374 patients was performed. The main primary indication for BAV was a bridge for TAVI (n = 185, 49.4%). Other indications included a bridge for AVR (n = 26, 6.9%) and rescue procedure in hemodynamically unstable patients (n = 139, 37.2%). The mortality rate at 30 days, 6 and 12 months was 10.4%, 21.6%, 28.3%, respectively. In rescue patients, the death rate raised to 66.9% at 12 months. A significant improvement in symptoms was confirmed after BAV, after 30 days, 6 months, and in survivors after 1 year (p < 0.05 for all). Independent predictors of 12-month mortality were baseline STS score [HR (95% CI) 1.42 (1.34 to 2.88), p < 0.0001], baseline LVEF <20% [HR (95% CI) 1.89 (1.55–2.83), p < 0.0001] and LVEF <30% at 1 month [HR (95% CI) 1.97 (1.62–3.67), p < 0.0001] adjusted for age/gender. In everyday clinical practice in the TAVI era, there are still clinical indications to BAV a standalone procedure as a bridge to surgery, TAVI or for urgent high risk non-cardiac surgical procedures. Patients may improve clinically after BAV with LV function recovery, allowing to perform final therapy, within limited time window, for severe AS which ameliorates long-term outcomes. On the other hand, in patients for whom an isolated BAV becomes a destination therapy, prognosis is extremely poor.

BAPST. A Combo of Common use drugs as metabolic therapy of cancer—a theoretical proposal.

: Advances in cancer therapy have yet to impact worldwide cancer mortality. Poor cancer drug affordability is one of the factors limiting mortality burden strikes. Up to now, cancer drug repurposing had no meet expectations concerning drug affordability. The three FDA-approved cancer drugs developed under repurposing -all-trans-retinoic acid, arsenic trioxide, and thalidomide- do not differ in price from other drugs developed under the classical model. Though additional factors affect the whole process from inception to commercialization, the repurposing of widely used, commercially available, and cheap drugs may help. This work reviews the concept of the malignant metabolic phenotype and its exploitation by simultaneously blocking key metabolic processes altered in cancer. We elaborate on a combination called BAPST, which stands for the following drugs and pathways they inhibit: Benserazide (glycolysis), Apomorphine (glutaminolysis), Pantoprazole (Fatty-acid synthesis), Simvastatin (mevalonate pathway), and Trimetazidine (Fatty-acid oxidation). Their respective primary indications are: • Parkinson's disease (benserazide and apomorphine). • Peptic ulcer disease (pantoprazole). • Hypercholesterolemia (simvastatin). • Ischemic heart disease (trimetazidine). When used for their primary indication, the literature review on each of these drugs shows they have a good safety profile and lack predicted pharmacokinetic interaction among them. Most importantly, the inhibitory enzymatic concentrations required for inhibiting their cancer targets enzymes are below the plasma concentrations observed when these drugs are used for their primary indication. Based on that, we propose that the regimen BAPTS merits preclinical testing.