bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacy student contribution to direct patient care during inpatient hospital experiential rotations: a scoping review
Authors: Kennie-Kaulbach Natalie , Cameron Karen , Humphrey Mari , Donovan Cortney , Isenor Jennifer E , Toombs Kent , Fernandes Olavo A
Published: August 2023

Objectives

The aim of this scoping review was to identify and characterise pharmacy students’ contributions to extend pharmacist’s direct patient care during inpatient hospital experiential rotations.

Methods

A search of PubMed, Embase and CINAHL databases from 2000 to July 2021 was conducted. Articles were included if they involved pharmacy students during experiential rotations, described student’s contribution to direct patient care in the inpatient hospital setting, and reported outcomes. Included articles were categorised according to clinical pharmacy key performance indicators (cpKPIs) and non-cpKPI care activities. Students’ contributions to reported outcomes were extracted and summarised.

Key findings

Thirty-six of 1182 identified articles were included which were either descriptive or quasi-experimental design. Studies reported student involvement in the delivery of single or multiple cpKPIs: medication reconciliation on admission (n = 13), pharmaceutical care (n = 13), interprofessional care rounds (n = 4), patient education during hospital stay (n = 6), medication reconciliation at discharge (n = 7) and patient education at discharge (n = 10). Eight studies reported student involvement in non-cpKPI activities, including clinical interventions (n = 5), clinical services (n = 2) and postdischarge follow-up (n = 1). Reported outcomes included service measure counts, process and clinical outcome measures.

This review identified the contributions of pharmacy students in the provision of a range of direct patient care services and associated outcomes during experiential rotations in the inpatient hospital setting. Students delivering care as part of the pharmacy team as ‘care extenders’ has the potential to expose more patients to key pharmacist activities that have been linked to demonstrated positive outcomes.
Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018
Authors: Jaha Bashkim , Schenkel Corinne D , Jörimann Lisa , Huber Michael , Zaheri Maryam , Neumann Kathrin , Leemann Christine , Calmy Alexandra , Cavassini Matthias , Kouyos Roger D , Günthard Huldrych F , Metzner Karin J ,   Swiss HIV Cohort Study, Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Kusejko K , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: August 2023

Background

Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA.

Objectives

A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia.

Methods

Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs).

Results

Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs.

Conclusions

We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.
Effect of dapagliflozin on COVID-19 infection and risk of hospitalization
Authors: Salgado-Barreira Angel , Seijas-Amigo Jose , Rodriguez-Mañero Moises , Piñeiro-Lamas María , Eiras Sonia , Cordero Alberto , Gonzalez-Juanatey Jose Ramon , Figueiras Adolfo
Published: August 2023

Background

Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection.

Methods

We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model.

Results

We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65–1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34–4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53–3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40–1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05–1.62; P = 0.015).

Conclusions

Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.
Alkylation of nucleobases by 2-chloro-N,N-diethylethanamine hydrochloride (CDEAH) sensitizes PARP1-deficient tumors
Authors: Wie Minwoo , Khim Keon Woo , Groehler IV Arnold S , Heo Soomin , Woo Junhyeok , Son Kook , Lee Eun A , Ra Jae Sun , Hong Sung You , Schärer Orlando D , Choi Jang Hyun , Myung Kyungjae
Published: August 2023

Targeting BRCA1- and BRCA2-deficient tumors through synthetic lethality using poly(ADP-ribose) polymerase inhibitors (PARPi) has emerged as a successful strategy for cancer therapy. PARPi monotherapy has shown excellent efficacy and safety profiles in clinical practice but is limited by the need for tumor genome mutations in BRCA or other homologous recombination genes as well as the rapid emergence of resistance. In this study, we identified 2-chloro-N,N-diethylethanamine hydrochloride (CDEAH) as a small molecule that selectively kills PARP1- and xeroderma pigmentosum A-deficient cells. CDEAH is a monofunctional alkylating agent that preferentially alkylates guanine nucleobases, forming DNA adducts that can be removed from DNA by either a PARP1-dependent base excision repair or nucleotide excision repair. Treatment of PARP1-deficient cells leads to the formation of strand breaks, an accumulation of cells in S phase and activation of the DNA damage response. Furthermore, CDEAH selectively inhibits PARP1-deficient xenograft tumor growth compared to isogenic PARP1-proficient tumors. Collectively, we report the discovery of an alkylating agent inducing DNA damage that requires PARP1 activity for repair and acts synergistically with PARPi.
Barriers to research productivity amongst postgraduate trainees: results from a survey of 333 medical and surgical residents
Authors: Bakhshi Saqib K , Abdul Rahim Komal , Merchant Asma A H , Afzal Noreen , Qadeer Shaikh Namra , Noorali Ali A , Lakhdir Maryam P A , Mahmood Saad B Z , Tariq Muhammad , Haider Adil H
Published: August 2023

Purpose

We aimed to determine the perceptions of, barriers to, and predictors of research engagement amongst residents at a national level in Pakistan.

Methods

This cross-sectional study used REDCap for online survey dissemination to residents from 12 institutes accredited by the national accreditation body (College of Physicians and Surgeons Pakistan) for core medical and surgical specialties. Logistic regression was used to estimate associations between likelihood of publications and participant characteristics.

Results

The response rate was 79% (333/423), with 171 (51%) medical and 162 (49%) surgical residents. The mean ± standard deviation age was 28.8 ± 2.7 years; 137 (41%) were males and 195 (59%) females. More than half the residents, 202 (61%), had received research training, but 189 (57%) scored <33% on basic research knowledge. While most residents agreed on the positive impact of research on their careers (P = .012) and realized that they should be involved in it (P = .33), they also strongly believed that it was difficult to engage in research during training (P < .01). Only 60 (18%) trainees had published a paper in local and 37 (11%) in international journals, respectively. The most significant barriers to conducting research included time limitation due to clinical work, lack of financial support, and unavailability of data (P < .01).

Conclusion

Residents have a positive attitude towards research. However, research engagement among residents is low. Improving research mentorship and creating systems that enable protected time and institutional access to data are needed to increase research output of postgraduate trainees.

Key messages What is already known on this topic Postgraduate trainees benefit academically from research conducted during residency training. However, in low- and middle-income countries like Pakistan, research output among residents has remained low over the years. The nation has consistently produced very little research. What this study adds The current study helped shed light on the reasons for low research productivity amongst medical and surgical residents in Pakistan. How this study might affect research, practice, or policy The potential predictors for low research involvement highlighted in this study necessitate modification of the existing national residency curriculum to increase research engagement and productivity among residents. Not only can the potential factors be improved, but the study also helps in bringing stakeholders’ attention to increasing research opportunities in Pakistan.
Major cardiovascular disease risk in men with testosterone deficiency (hypogonadism): appraisal of short, medium and long-term testosterone therapy – a narrative review
Authors: Traish Abdulmaged M
Published: August 2023

Introduction

Low testosterone (T) levels are associated with obesity, metabolic syndrome, type 2 diabetes mellitus and altered lipid profiles, thus contributing to increased cardiovascular disease risk. Hence T deficiency has a detrimental effect on men’s vascular health, quality of life and increased mortality.

Objectives

This review aims to present summary of data in the contemporary clinical literature pertaining to the benefits of T therapy in clinical studies with varying durations on vascular health in men with T deficiency.

Methods

A Medline search using PubMed and EMBASE was performed using the following key words: “testosterone deficiency,” “testosterone therapy,” major cardiovascular adverse events”, “cardiovascular disease”. Relevant studies were extracted, evaluated, and analyzed. We evaluated findings from clinical trials, observational studies and systematic reviews and meta-analyses to develop a comprehensive account of the critical role of T in maintaining vascular health.

Results

Considerable evidence beginning with studies published in 1940s concomitant with findings from the utmost recent clinical studies suggests a clinical value of T therapy in maintaining vascular health and reducing cardiovascular mortality. The current scientific and clinical evidence demonstrates strong relationship between low circulating T levels and risk of cardiovascular disease and T therapy is deemed safe in men with hypogonadism when given in the physiological range with no apparent harm.

Conclusion

What emerges from the current clinical literature is that, irrespective of the length of study durations, testosterone therapy provides significant health benefits and reduces risk of cardiovascular disease. More important is that data from many observational and registry studies, demonstrated that longer durations of testosterone therapy were associated with greater health benefits and reduced cardiovascular risk. T therapy in men with T deficiency reduces the incidence of major adverse cardiovascular events attributed to improving overall metabolic function.
Baxdrostat: An Aldosterone Synthase Inhibitor for the Treatment of Systemic Hypertension
Authors: Dey Subo , Frishman William H. , Aronow Wilbert S.
Published: August 2023

Systemic hypertension remains one of the leading cause of morbidity and mortality in the United States and throughout the world. Baxdrostat (CIN-107), a new drug developed by Roche is a selective aldosterone synthase inhibitor that is being evaluated as one of the potential treatments for hypertension, especially in patients with drug treatment-resistant hypertension. An increased level of aldosterone is associated with inflammation, systemic hypertension, and organ fibrosis, contributing to adverse cardiovascular events. A phase 2 trial, BrigHTN, showed promising results in demonstrating the efficacy of baxdrostat, where The HALO (efficacy and safety of baxdrostat in patients with uncontrolled hypertension) trial did not demonstrate any blood pressure-lowering benefit of baxdrostat when compared with the placebo. Several additional studies are now underway to evaluate the effectiveness of baxdrostat as an anti-hypertensive agent.
First Branchial Cleft Fistula Piercing through the Main Trunk of the Facial Nerve
Authors: Moriyama Masazumi , Kuwahara Kosuke , Nakagawa Masahiro , Kamochi Hideaki
Published: August 2023

First branchial cleft fistulas are congenital malformations that result from the incomplete closure of the ectodermal portion of the first branchial cleft. These fistulas typically appear as small pits or subcutaneous masses in the upper neck and cheek and can cause pain due to infection and inflammation. Surgical excision is the most effective treatment, but special attention is necessary to avoid facial nerve injury due to the proximity of the lesion to the nerve and variations in their arrangement. Here, we report the successful treatment of a first branchial cleft fistula piercing through the main trunk of the facial nerve in a 3-year-old girl. Intraoperative findings revealed that the fistula in the parotid gland opened into the cheek area from the ear canal. Identification of the facial nerve trunk was challenging due to the malformation of the lower end of the auricular cartilage, which is an anatomical landmark of the facial nerve. The trunk of the facial nerve was divided proximally by the fistula and merged just past the fistula. Preoperative magnetic resonance is important for determining the fistula location, surrounding anatomical variations, and fistula-facial nerve arrangement. Furthermore, early surgical treatment should be considered to prevent tissue scarring and adhesion due to infection, which can lead to facial nerve injury.
A Methodology for Calculating Inhalation Dose to Public Health Personnel Exposed to Material Resuspended from Evacuees Following the Detonation of a Fission Device
Authors: Anspaugh Lynn R. , Mauro John , Briggs Nicole , Porrovecchio Joseph , Amann William , Salame-Alfie Adela , Ansari Armin
Published: August 2023

Following a nuclear fission event, there likely would be a large number of contaminated persons who would seek assistance at community reception centers to be established outside the affected area. This paper provides a methodology for calculating inhalation doses to public health and other response personnel at such facilities who would be receiving and assisting potentially contaminated persons from whom particles can be resuspended. Three hypothetical facilities were considered: the Base Case is a rather small room with no forced air ventilation. The Preferred Case, which is more realistic, is a mid-sized room with an operating HVAC system with air being recirculated through a filter. The Gymnasium Case has only fresh air intake. Initial bounding calculations for the Base Case indicated the need for pre-screening of arrivals to avoid unacceptable doses to staff. The screening criterion selected was 1.67 × 106 Bq m−2. Calculations are presented for radionuclide concentrations in air, dose to staff from inhalation, and how exposures and the resulting doses can be altered by air-turnover rates and the use of filters with varying efficiency. Doses are presented for various arrival times and for both plutonium- and uranium-fueled detonations. The highest calculated dose via inhalation with no respiratory protection was 0.23 mSv for the Base Case. The more important radionuclides contributing to dose with exposure starting at day D + 1 were 239Np and 133I. At day D + 30, 131I and 140Ba were the more important dosimetrically. The variable creating the highest uncertainty was the slough-off factor for resuspension of contamination from people arriving at the reception center.
Comparative Evaluation of RT-PCR Kits Available in Sri Lanka for Diagnosis of COVID-19
Authors: Amarasinghe Kanchana P. , Murugananthan Arumugam , Amalraajan Ponnuthurai T. , Thavaththurai Mithusha , Ravindran Gayathri , Murugananthan Kalamathy , Gunathilake Shakila K.
Published: August 2023

Identification of gene targets by real-time reverse transcriptase PCR (rRT-PCR) is considered as the gold standard for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although many commercial rRT-PCR kits are currently used in Sri Lanka, analytical performance of these kits have not been investigated adequately. Therefore, the objective of the present study was to evaluate the analytical performance of rRT-PCR kits used in the laboratory of the Faculty of Medicine, University of Jaffna (five kits). Performance of the five rRT-PCR kits selected for this study was compared with the CDC 2019-Novel Coronavirus (2019-nCoV) RT-PCR Diagnostic Panel as reference standard. The sensitivity, specificity, positive predictive value, negative predictive value and Cohen’s κ coefficient of the five different commercial kits were analyzed. SARS-CoV-2 positive (62) and negative (32) respiratory samples collected respectively from symptomatic individuals and asymptomatic healthy individuals were used in this study. Comparison of the cycle threshold (Ct) values of the five commercial kits revealed heterogeneity. Among them, the TaqPathTM kit showed the highest sensitivity (98.4%) and interrater reliability (0.976). The HBRT-COVID-19 kit showed the lowest sensitivity (91.9%), specificity (93.7%) and interrater reliability (0.838). Although the five RT-PCR kits exhibited varying sensitivity, specificity and Ct values, all of them are suitable for the routine diagnosis of SARS-CoV-2 infections as all values were higher than 90%.
Endoscopic treatment of gastroesophageal reflux: a narrative review
Authors: Lopes Samuel Oliveira , Gonçalves Ana Raquel , Macedo Guilherme , Santos-Antunes João
Published: August 2023

Gastroesophageal reflux disease (GERD) is a common chronic disease that affects one-third of the population worldwide. In recent years, there have been significant advances for diagnostic workup, which leads to better identification of reflux-related complications. Classically, the mainstay of therapy has been proton pump inhibitor and lifestyle and dietary modifications. For refractory GERD the gold-standard therapies are surgical antireflux procedures. Recently, endoscopic procedures have emerged as safe and efficient alternatives to surgery. These could represent a less invasive approach, with scarce morbidity and with a well-tolerated profile. Each of the existing endoscopic techniques for the treatment of GERD are addressed in this report, highlighting their potential advantages, aiming at helping decide the best management of these patients. Future studies, with larger numbers of patients, may allow a definitive role for these techniques in the management of GERD to be established.
Exploring the Difficulties and Strategies of Family Caregivers in Caring for Patients With Dementia in Acute Care Wards
Authors: CHEN Ko-Xin , HSU Pei-Chen , LIN Jong-Ni , LEE Feng-Ping , WANG Jing-Jy
Published: August 2023

Background

Providing appropriate care to patients with dementia in acute care settings can be a challenge for healthcare professionals. A key factor is working closely with family caregivers.

Purpose

This study aims to explore the difficulties and strategies involved in caring for patients with dementia who have been admitted to an acute care ward from the perspective of family caregivers.

Methods

Exploratory research was conducted using a qualitative data collection approach. Data were collected by means of in-depth interviews carried out with participants. Semistructured interviews were conducted with nine participants. Content analysis was performed to analyze the data.

Results

A number of themes and subthemes were identified based on the primary research purposes. The first theme is “vicious cycle due to multiple factors,” with the following subthemes: (a) communication disturbance, (b) endless worries, (c) inadequate care skills of paid caregivers, and (d) physical and psychological exhaustion. The second theme is “do everything,” with the following subthemes: (a) management of the behavioral and psychological symptoms of dementia, (b) constant accompaniment of the patient, and (c) seeking sources of support.

Conclusions/Implications for Practice

The results may be used to help healthcare professionals better anticipate the difficulties faced by family caregivers while providing assistance to patients with dementia and understand the related strategies they use. Acute care wards should consider the specific needs of family caregivers to ensure patients with dementia receive adequate care from the relevant parties in the ecological care chain during the care process.
Sarcopenic obesity may predict worse liver regeneration after right graft living donor liver transplantation
Authors: Ali Deeb Aladdin , Settmacher Utz , Fritsch Johannes , Dondorf Felix , Rohland Oliver , Rauchfuß Falk
Published: August 2023

Sarcopenic obesity impairs the outcome after liver transplantation. The effect of this on liver regeneration has not yet been studied. The aim of this study was to evaluate the potential effect of body composition changes on liver volume gain after living donor liver transplantation. We observed liver regeneration in 100 patients who underwent living donor liver transplantation using right lobe grafts (Segments V-VIII). Liver volumetry and body composition analysis were performed based on CT images with special software. The gain of liver volume was calculated between 2 points in time considering the absolute and percentage values: before surgery and early after surgery, with a median time of 10 days. Pearson’s correlation and multivariate analysis using stepwise multiple regression were used to examine the potential correlation between body composition and liver volume gain. The liver volume increase was significantly negatively correlated with adipose tissue in the body stem (r = −0.4, p < 0.001) and positively correlated with psoas mass (r = 0.24, p = 0.02). These results correspond with those of the multiple regression analysis, which indicated adipose tissue (ß = −1.0, p < 0.001) and psoas mass (ß = 0.12, p < 0.001). The presence of malignancy as an indication for liver transplantation was another significant independent factor negatively affecting liver growth (ß = −13.1, p = 0.046). Sarcopenic obesity predicts an impaired liver volume increase after living donation. This could worsen the postoperative outcome. The role of alimentary interventions and exercises in improving body composition and thus postoperative outcome should be evaluated through prospective interventional studies.
Effect of Aortic Valve Opening Pattern on Endothelial Function After Continuous-Flow Left Ventricular Assist Device Implantation
Authors: Kaya Ersin , Kocabaş Umut , Şimşek Evrim , Nalbantgil Sanem , Engin Çağatay , Özbaran Mustafa , Akilli Azem
Published: August 2023

This study aimed to evaluate the effects of aortic valve opening patterns on endothelial functions in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. This study included 43 patients who underwent CF-LVAD implantation and 35 patients with heart failure reduced ejection fraction (HFrEF; control group). The CF-LVAD group was divided into three subgroups based on aortic valve opening patterns: open with each beat, intermittently opening, and not opening groups. Flow-mediated dilatation (FMD) and pulsatility index (PI) were compared before and 3 months after CF-LVAD implantation. Cardiopulmonary exercise test (CPET) and 6 minute walk test (6-MWT) scores were measured at baseline and follow-up in the CF-LVAD group. The mean FMD and PI of patients in the CF-LVAD group reduced 3 months after implantation. Patients with intermittently opening and not opening aortic valves had worse endothelial function at follow-up. Before and 3 months after implantation FMD% did not significantly differ in patients whose aortic valves were open with each beat (4.72 ± 1.06% vs. 4.67 ± 1.16%, p = 0.135). Pulsatility index changes paralleled FMD changes. Cardiopulmonary exercise test and 6-MWT scores improved after implantation but without significant differences between subgroups. Maintaining normal aortic valve function after CF-LVAD implantation may reduce endothelial dysfunction; however, larger studies are needed for long-term clinical effects.
Smaller Return Cannula in Venoarterial Extracorporeal Membrane Oxygenation Does Not Increase Hemolysis: A Single-Center, Cohort Study
Authors: Joyce Patrick R. , Hodgson Carol L. , Bellomo Rinaldo , Gregory Shaun D. , Raman Jaishankar , Stephens Andrew F. , Taylor Kieran , Paul Eldho , Wickramarachchi Avishka , Burrell Aidan
Published: August 2023

The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin (pfHb). Moderate hemolysis is defined as having pfHb 0.05–0.10 g/L and severe hemolysis as having pfHb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs. 6; p = 0.39) and severe hemolysis (0 vs. 3; p = 0.27), nor was the pfHb level significantly different at 4 hours (0.086 ± 0.096 vs. 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs. 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.
Heart–Lung Transplantation From Donation After Circulatory Death Using Mobile Normothermic Regional Perfusion
Authors: Spencer Philip J. , Saddoughi Sahar A. , Choi Kukbin , Dickinson Timothy A. , Richman Adam , Reynolds F. Alex , Villavicencio Mauricio A.
Published: August 2023

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center.
Clinical Outcomes of Left Ventricular Assist Device Pump Infection
Authors: Imaoka Shusuke , Samura Takaaki , Yoshioka Daisuke , Kawamura Masashi , Kawamura Takuji , Toda Koichi , Miyagawa Shigeru
Published: August 2023

Few studies have focused on the clinical outcomes and risk factors of left ventricular assist device (LVAD) pump infection, and no standard treatment for LVAD pump infection has been established. Therefore, we used a therapeutic flowchart to manage LVAD pump infections. We retrospectively evaluated 220 patients who underwent continuous-flow LVAD implantation between January 2005 and March 2021 at Osaka University, Japan. First, we performed wound debridement, negative-pressure wound therapy, antibiotic treatment, and omental flap transposition. Subsequently, we administered conservative treatment, scheduled implantable LVAD exchange, or emergent removal of the implantable LVAD and exchange for extracorporeal LVAD or percutaneous LVAD (IMPELLA). Pump infections occurred in 32 patients. The survival rates of patients with pump infections during LVAD support were 93%, 74%, and 61% at 180 days, 1 year, and 2 years after LVAD pump infection, respectively. Fifteen patients underwent successful heart transplantation. Bridge-to-bridge surgery, preoperative use of venoarterial extracorporeal membrane oxygenation or percutaneous LVAD, high lactate dehydrogenase levels, and driveline infection were significantly associated with pump infection. Our study reveals that poor preoperative condition and driveline infection were significant risk factors for LVAD pump infection.
Interval Colorectal Cancer in Inflammatory Bowel Disease
Authors: Da Cunha Teresa , Vaziri Haleh
Published: August 2023

Inflammatory bowel disease (IBD) increases the risk of dysplasia and colorectal cancer (CRC). Moreover, colitis-associated CRC is responsible for a disproportionate number of CRC-related mortality. For this reason, societies recommend screening and surveillance colonoscopy as the standard of care for patients with ulcerative colitis and Crohn’s colitis. Nonetheless, interval cancer defined as CRC detected within the appropriate surveillance interval might still occur despite following guideline recommendations. Even though there is limited data on risk factors associated with interval CRC in IBD, patient and disease-associated factors and technical aspects of the surveillance might play a role. This review aims to provide information on the epidemiology of interval CRC in IBD, the factors that might be associated with its occurrence, and the challenges of CRC screening and dysplasia management in patients with IBD.
Red cell extracellular vesicles and coagulation activation pathways
Authors: Noubouossie Denis F. , Key Nigel S.
Published: August 2023

Purpose of review

Packed red blood cells (PRBCs) are the most commonly transfused blood products. Preparation of PRBCs requires blood collection from donors, processing, and storage prior to transfusion to recipients. Stored red blood cells (RBCs) undergo structural and metabolic changes collectively known as the storage lesion. RBC extracellular vesicles (sREVs) are released in PRBC units during storage, and are transfused along with intact RBCs into recipients. For several decades, extracellular vesicles have been the focus of intense research, leading to the discovery of a wide variety of endogenous biological properties that may impact numerous physiologic and/or pathologic pathways.

Recent findings

This study reviews the characteristics of extracellular vesicles present in PRBC units and the impact of prestorage and pretransfusion processing, as well as storage conditions, on their generation. Importantly, we discuss recently described interactions of sREVs with coagulation pathways and related interplay with inflammatory pathways in vitro and in vivo using animal models.

Extracellular vesicles present in stored PRBC units are capable of activating coagulation pathways. However, it remains unclear whether this affects clinical outcomes in recipients of PRBC units. Further understanding of these pathways and their relationship to any adverse outcomes may yield novel strategies to mitigate complications of blood transfusion.
A new SPRING in lipid metabolism
Authors: Hendrix Sebastian , Zelcer Noam
Published: August 2023

Purpose of review

The SREBP transcription factors are master regulators of lipid homeostasis owing to their role in controlling cholesterol and fatty acid metabolism. The core machinery required to promote their trafficking and proteolytic activation has been established close to 20 years ago. In this review, we summarize the current understanding of a newly identified regulator of SREBP signaling, SPRING (formerly C12ORF49), its proposed mechanism of action, and its role in lipid metabolism.

Recent findings

Using whole-genome functional genetic screens we, and others, have recently identified SPRING as a novel regulator of SREBP signaling. SPRING is a Golgi-resident single-pass transmembrane protein that is required for proteolytic activation of SREBPs in this compartment. Mechanistic studies identified regulation of S1P, the protease that cleaves SREBPs, and control of retrograde trafficking of the SREBP chaperone SCAP from the Golgi to the ER as processes requiring SPRING. Emerging studies suggest an important role for SPRING in regulating circulating and hepatic lipid levels in mice and potentially in humans.

Current studies support the notion that SPRING is a novel component of the core SREBP-activating machinery. Additional studies are warranted to elucidate its role in cellular and systemic lipid metabolism.
Dysphagia and dementia: a ‘double dilemma’
Authors: Leonard Rebecca
Published: August 2023

Purpose of review

Dementia and its variants, including Alzheimer's disease, become more prevalent with age. Dysphagia, that is, difficulty swallowing, also occurs with aging, and is often associated with dementia. Currently, there is no cure for dementia, and dysphagia, unrecognized or untreated, can have life-altering, even fatal consequences. Prolonged ability to eat safely and effectively could contribute to improved quality of life in a fragile population. In this review, difficulties associated with the management of dysphagia in individuals with dementia, as well as promising possibilities for continued investigation, will be discussed.

Recent findings

Recent reports point to unique problems related to understanding the comorbidities of dysphagia and dementia. These include delays in identifying dysphagia in affected individuals, as well as a lack of prevalence data for dysphagia in types and stages of dementia, or according to setting, for example, residential center, hospital. Emphasis on new tools, and new applications of existing tools, are needed.

New evidence not only underscores complexities and shortcomings of our understanding of dysphagia in dementia but also points to existing applications with potential for improving the situation, and new investigational directions that may elaborate our further understanding of these comorbidities.
Advances in and applications of imaging and radiomics in head and neck cancer survivorship
Authors: Wishart Laurelie R. , Ward Elizabeth C. , Galloway Graham
Published: August 2023

Purpose of Review

Radiological imaging is an essential component of head/neck cancer (HNC) care. Advances in imaging modalities (including CT, PET, MRI and ultrasound) and analysis have enhanced our understanding of tumour characteristics and prognosis. However, the application of these methods to evaluate treatment-related toxicities and functional burden is still emerging. This review showcases recent literature applying advanced imaging and radiomics to the assessment and management of sequelae following chemoradiotherapy for HNC.

Recent findings

Whilst primarily early-stage/exploratory studies, recent investigations have showcased the feasibility of using radiological imaging, particularly advanced/functional MRI (including diffusion-weighted and dynamic contrast-enhanced MRI), to quantify treatment-induced tissue change in the head/neck musculature, and the clinical manifestation of lymphoedema/fibrosis and dysphagia. Advanced feature analysis and radiomic studies have also begun to give specific focus to the prediction of functional endpoints, including dysphagia, trismus and fibrosis.

There is demonstrated potential in the use of novel imaging techniques, to help better understand pathophysiology, and improve assessment and treatment of functional deficits following HNC treatment. As larger studies emerge, technologies continue to progress, and pathways to clinical translation are honed, the application of these methods offers an exciting opportunity to transform clinical practices and improve outcomes for HNC survivors.
Transitions in tracheostomy care: from childhood to adulthood
Authors: Edwards Louise , McRae Jackie
Published: August 2023

Purpose of review

The purpose of this review is to explore the evidence around children and young people who require a tracheostomy and transition into adult services, reflecting on the challenges and considerations for clinical practice as these needs increase.

Recent findings

There are a lack of data on the incidence and prevalence of children and young people with a tracheostomy transitioning to adult services for ongoing care. There are significant variations in care needs, technology and previous experiences that demand more than a simple handover process. Examples of service models that support the transition of care exist, however these lack specificity for children and young people with a tracheostomy.

Further exploration of the needs of children and young people requiring airway technology is indicated, particularly considering the short and long-term education, health, and social care needs.
Helicobacter pylori Antimicrobial Resistance Using Next-Generation Sequencing in Stool Samples in a Pediatric Population
Authors: Bonilla Silvana , Goldsmith Jeffrey , Mitchell Paul , Bousvaros Athos
Published: August 2023

Helicobacter pylori (H pylori) eradication rates have declined globally, stressing the importance of antimicrobial susceptibility testing to inform treatment. Molecular tests such as next-generation sequencing (NGS) provide susceptibility data for the antibiotics used in the treatment of H pylori in a noninvasive, effective, and rapid manner. We obtained stool susceptibility testing using a novel NGS-based analysis and compared results with the current “gold standard” of gastric biopsy culture via agar dilution in 20 pediatric patients with evidence of H pylori in gastric biopsies. Stool NGS-based antimicrobial susceptibility analysis was highly concordant with agar dilution for no resistance (100% agreement), as well as clarithromycin, levofloxacin, and amoxicillin resistance (100%, 67%, and 100% agreement, respectively) but not concordant for metronidazole in our cohort of patients. Future studies involving a larger number of patients and geographical regions are needed to further validate this analysis.
CenteringPregnancy: A Review of Implementation and Outcomes
Authors: Moyett Julia M. , Ramey-Collier Khaila , Zambrano Guevara Linda M. , MacDonald Amy , Kuller Jeffrey A. , Wheeler Sarahn M. , Dotters-Katz Sarah K.
Published: August 2023

Importance

CenteringPregnancy (CP) is a model for group prenatal care associated with improved perinatal outcomes for preterm birth and low birthweight, increased rates of breastfeeding, and higher rates of patient and clinician satisfaction.

Objective

The study aims to review the literature related to perinatal outcomes associated with CP, benefits and barriers to implementation, and utility of the model.

Evidence

An electronic-based search was performed in PubMed using the search terms “CenteringPregnancy” OR “Centering Pregnancy,” revealing 221 articles.

Results

The CP model improves patient centeredness, efficiency, and equality in prenatal care. Challenges include administrative buy-in, limited resources, and financial support. Multisite retrospective studies of CP demonstrate improved maternal, neonatal, postpartum, and well-being outcomes, especially for participants from minority backgrounds; however, prospective studies had mixed results. CenteringPregnancy is feasibly implemented with high tenet fidelity in several low- and middle-income settings with improved perinatal outcomes compared with traditional care.

Conclusions

CenteringPregnancy is feasible to implement, largely accepted by communities, and shows positive qualitative and quantitative health outcomes. This body of literature supports CP as a potential tool for decreasing racial inequalities in prenatal access, quality of care, and maternal mortality. Further investigation is necessary to inform obstetric clinicians about the potential outcome differences that exist between group and traditional prenatal care.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to explain the core components and structure of the CP model; discuss the benefits and challenges of CP implementation and its impact on perinatal and neonatal outcomes; and describe the effect of CP on racial/ethnic disparities in perinatal outcomes.
Perfusion Index Variations in Children With Septic Shock: Single-Center Observational Cohort Study in India
Authors: AV Lalitha , Kuzhikkombil Mani Siji , Ghosh Santu
Published: August 2023

OBJECTIVES:

To study in children with septic shock: 1) variation in peripheral perfusion index (PI), which is a derived variable from pulse oximetry; 2) correlation between PI and lactate concentration; and 3) exploratory diagnostic evaluation between mortality and PI.

DESIGN:

Prospective observational study (from October 2018 to March 2020).

SETTING:

Pediatric emergency department and PICU of a tertiary hospital in India.

PATIENTS:

Children (1 mo to 16 yr old) with septic shock.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Data collected included demographic, clinical, laboratory, and outcome-related variables. Hemodynamic variables like heart rate, mean arterial pressure, and PI, along with serum lactate were recorded at specified intervals. A total of 112 children with septic shock were recruited, with median (interquartile range [IQR]) age of 50 (IQR 12,118.5) months and 65 of 112 (58%) were male children. Overall mortality was 25 of 112 (22%). At admission, the median PI was 0.6 (IQR –0.30, 0.93), and we used PI less than or equal to 0.6 to define a “critical PI.” Of 61 children with critical PI at admission, 26 of 61 increased above this threshold by 6 hours. We observed a negative correlation between PI and lactate, at admission (r = –0.27; 95% CI, –0.44 to –0.08; p = 0.006) and at 6 hours (r = –0.21; 95% CI, –0.39 to –0.02; p = 0.03). In the exploratory analysis, a PI cutoff of less than or equal to 0.6 at 6 hours had area under the receiver operating curve of 0.74 (95% CI, 0.60–0.88). That is, with a 70% sensitivity and 81% specificity for mortality, the performance of such a test in our population (pre-to-post-test probability) for mortality would be 0.22–0.51.

CONCLUSIONS:

We have used pulse oximetry-derived PI in children presenting with septic shock and found that the value is negatively correlated with a rise in serum lactate concentration. However, the utility of using a critical threshold value in PI (≤ 0.6) after 6 hours of treatment to be indicative of later mortality has considerable uncertainty.
Overdiagnosis of Newborn Hyperbilirubinemia: A Natural Experiment in Quality Improvement Fundamentals
Authors: Stirling Kara J. , Kaempf Joseph W. , Wang Lian , Luzzi Veronica I. , McDonald John V.
Published: August 2023

Introduction:

Two hospitals noted increased newborn hyperbilirubinemia coinciding with an undisclosed total serum bilirubin (TSB) assay change. Clinicians rapidly applied quality improvement methodologies to ascertain increased jaundice evaluations, readmissions, and possible safety issues.

Methods:

In January 2020, 2 hospitals (A and B) transitioned to a new method of measuring TSB using a new clinical chemistry analyzer (Siemens Atellica CH), which measured TSB by vanadate oxidase assay instead of the previous diazo assay. Five affiliated hospitals (C–G) continued to utilize the diazo assay. This natural experiment led to a comparison of data across the 7 hospitals. We analyzed: (1) TSB levels, (2) hospital hyperbilirubinemia readmissions, and (3) paired TSB measurements comparing the diazo assay and vanadate oxidase method.

Results:

Compared to the 2019 baseline, Hospitals A and B had a significant increase in TSBs ≥17.0 mg/dl and TSBs ≥20 mg/dl in 2020; Hospitals C–G did not. Readmissions for phototherapy significantly increased in hospitals A and B in 2020 compared to 2019. Paired blood samples showed bias-elevated TSBs by vanadate assay compared to the diazo method. By 2021, the laboratory resumed processing TSB samples by diazo assay, and the frequency of elevated TSBs and hyperbilirubinemia readmissions returned to 2019 levels.

Conclusions:

Factitious TSB elevation related to an assay change significantly increased newborn hyperbilirubinemia evaluations and phototherapy readmissions. Imbedded quality improvement methodologies of careful structure, process, and outcomes review hastened resolution.