Implementation of an international medical student pen-pal club:survey outcomes of perceptions in cultural competency and global health

Background:Pen-pal clubs(PPC)are used worldwide for students to learn about different cultures and other skillsets without the need for travel.Many medical students are interested in global health opportunities abroad but costs,scheduling,and other barriers allow few to participate in such experiences.It is important that medical students have nuanced global medical perspectives and can contribute to the global medical community.Objective:The purpose of this study is to demonstrate that an international medical student PPC improves medical students'perspectives of cultural competency and global health engagement.Methods:In 2021,a novel medical student PPC was established that began between an American and Japanese medical school.Following a shareholders meeting,it was decided that the number of medical schools involved globally be expanded through previous institutional affiliations and online presences.In total,the club connected 50 American medical students and 52 medical students from 17 high-and middle-income countries.The primary form of communication was online;pen-pals were encouraged to communicate monthly using provided topics,although frequency and way of communication was their discretion.In February 2022,American PPC members were emailed a qualitative survey to assess the PPC's impact.Results:The survey was completed by 42%of American PPC members,95%of which were 22-26 years.Participants were preclinical medical students,60%whom were female and the majority either white(47%)or Asian(43%).Overall,the PPC positively influenced American medical students'perception of global medicine,medical education,and their cultural competency after joining the PPC compared to prior(P=0.004).Conclusion:PPCs encourage medical students to think from a global perspective and foster open-mindedness within varying social and cultural contexts.Having a global communication platform for students during medical school education may be an additional way to train aspiring global leaders.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Seeing beneath the surface:Harnessing point-of-care ultrasound for internal jugular vein evaluation

Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.

Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

The Impact of a Prior Norwood Procedure on Cardiac Transplantation in Failed Fontan Physiology

Objective:The objective of this study was to compare cardiac transplant operative and postoperative courses of patients with failed Fontan physiology who were initially palliated with a Norwood(FFN)to those without a prior Norwood(FF).Methods:A single-institution retrospective review of all patients with Fontan failure who under-went cardiac transplantation from 2003–2021 was completed-22 underwent prior Norwood(FFN)and 11 did not(FF).Descriptive and inferential statistics were calculated for operative course and patient outcomes.Results:The operative course of the FFN cohort appeared to be more complex(not statistically significant,but clinically relevant)-this group exclusively experienced sternal re-entry events(3 of 22 patients)and concomitant neo-aor-tic reconstruction(6 patients),had a longer duration of surgery(median of 682 min vs.575.5 min),more time on circulatory arrest(median of 25.5 min vs.12.5 min),and more frequent use of open sternal management[50%of patients(11/22)vs.27.3%of patients(3/11)].Postoperatively,these patients underwent more mediastinal explora-tions[other than sternal closure;40.9%of patients(9/22)vs.18.2%of patients(2/11)],spent more time on mechanical ventilation(median of 5 days vs.2 days),had a longer length of stay(median of 30 days vs.19 days),and required more catheter-based re-interventions[22.7%of patients(5/22)vs.9.1%of patients(1/11)].Conclu-sion:Although underpowered,our results suggest that the operative course of FFN patients is more challenging,based mostly on neo-aortic arch issues.In turn,this likely leads to a more complex postoperative course.We are currently collaborating with other institutions to increase the cohort size and power of the study.

Point-of-care ultrasonography in cirrhosis-related acute kidney injury:How I do it

Discerning the etiology of acute kidney injury(AKI)in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes.The conventional approach of empiric albumin administration for suspected volume depletion may inadvertently lead to fluid overload.In the recent past,point-of-care ultrasonography(POCUS)has emerged as a valuable adjunct to clinical assessment,offering advantages in terms of diagnostic accuracy,rapidity,cost-effectiveness,and patient satisfaction.This review provides insights into the strategic use of POCUS in evaluating cirrhotic patients with AKI.The review distinguishes basic and advanced POCUS,emphasizing a 5-point basic POCUS protocol for efficient assessment.This protocol includes evaluations of the kidneys and urinary bladder for obstructive nephropathy,lung ultrasound for detecting extravascular lung water,inferior vena cava(IVC)ultrasound for estimating right atrial pressure,internal jugular vein ultrasound as an alternative to IVC assessment,and focused cardiac ultrasound for assessing left ventricular(LV)systolic function and identifying potential causes of a plethoric IVC.Advanced POCUS delves into additional Doppler parameters,including stroke volume and cardiac output,LV filling pressures and venous congestion assessment to diagnose or prevent iatrogenic fluid overload.POCUS,when employed judiciously,enhances the diagnostic precision in evaluating AKI in cirrhotic patients,guiding appropriate therapeutic interventions,and minimizing the risk of fluid-related complications.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery

BACKGROUND Currently,the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors,but they are not a cure,and some patients don’t respond well or refuse long-term use.Therefore,alternative therapies are needed to understand the disease and develop better treatments.Laparoscopic anti-reflux surgery(LARS)can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects.Successful LARS improves typical gastroesophageal reflux symptoms in most patients,main-ly by reducing the exposure time to gastric contents in the esophagus.Amelio-ration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack.AIM To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery.METHODS Of 22 patients with LARS(pre-and post/5.8±3.8 months after LARS)and 25 healthy controls(HCs)were included.All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy,during which esophageal biopsy samples were collected using endoscopic tech-niques.Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay.RESULTS Post-LARS samples showed significant increases in proinflammatory cytokines[interleukin(IL)-1β,interferon-γ,C-X-C chemokine ligand 2(CXCL2)],anti-inflammatory cytokines[CC chemokine ligand(CCL)11,CCL13,CCL17,CCL26,CCL1,CCL7,CCL8,CCL24,IL-4,IL-10],and homeostatic cytokines(CCL27,CCL20,CCL19,CCL23,C-CL25,CXCL12,migration inhibitory factor)compared to both HCs and pre-LARS samples.CCL17 and CCL21 levels were higher in pre-LARS than in HCs(P<0.05).The mRNA expression levels of AKT1,fibroblast growth factor 2,HRAS,and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS.CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs(P<0.05).CONCLUSION The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium.Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS.The anti-inflam-matory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated type early gastric cancer over 2 cm with R0 resection

BACKGROUND Endoscopic submucosal dissection(ESD)for over 2 cm in size undifferentiated type(UD type)early gastric cancer(EGC)confined to the mucosa is not only challenging,but also long-term outcomes are not well known.AIM To evaluate the long-term outcomes of ESD done for UD type EGCs confined to the mucosa over 2 cm in size and compare the results with those where the lesions were less than 2 cm.METHODS 143 patients with UD type EGC confirmed on histology after ESD at a tertiary hospital were reviewed.Cases with synchronous and metachronous lesions and a case with emergency surgery after ESD were excluded.A total of 137 cases were enrolled.79 cases who underwent R0 resection were divided into 2 cm or less(group A)and over 2 cm(group B)in size.RESULTS Among 79 patients who underwent R0 resection,the number in group A and B were 51 and 28,respectively.The mean follow-up period(SD)was 79.71±45.42 months.There was a local recurrence in group A(1/51,2%)and group B(1/28,3.6%)respectively.This patient in group A underwent surgery while the patient in group B underwent repeated ESD with no further recurrences in both patients.There was no regional lymph node metastasis,distant metastasis,and deaths in both groups.With R0 resection strategy for ESD on lesions over 2 cm,20.4%(28/137)of patients were able to avoid surgery compared with expanded indication.CONCLUSION If R0 resection is achieved by ESD,UD type EGCs over 2 cm also showed good and similar clinical outcomes as compared to lesions less than 2 cm when followed for over 5 years.With R0 resection strategy,several patients can avoid surgery.

Point-of-care ultrasound in nephrology:A private practice viewpoint

Point-of-care ultrasound(POCUS)is a limited ultrasound examination performed by the clinician at the bedside,emerging as a complement to physical examination across various medical specialties.In the field of nephrology,its integration has been gradual,primarily limited to guiding procedures like temporary dialysis catheter placement or,in some cases,diagnostic kidney ultrasounds.In reality,the assessment of hemodynamic status at the bedside holds immense value for nephrologists,yet there exists limited awareness among practitioners regarding its implementation.While there is a growing trend towards incorporating multiorgan POCUS training in fellowship programs,private practice nephrologists remain relatively uninformed.This discussion explores the untapped potential of POCUS as a valuable diagnostic tool in everyday nephrology practice,demonstrating its effectiveness in diverse clinical settings,ranging from medical wards to outpatient dialysis units.Additionally,we delve into the challenges hindering its widespread adoption and consider the future trajectory of this innovative approach.

Point-of-care ultrasonography spotlight:Could venous excess ultrasound serve as a shared language for internists and intensivists?

Point-of-care ultrasonography(POCUS),particularly venous excess ultrasound(VExUS)is emerging as a valuable bedside tool to gain real-time hemodynamic insights.This modality,derived from hepatic vein,portal vein,and intrarenal vessel Doppler patterns,offers a scoring system for dynamic venous congestion assessment.Such an assessment can be crucial in effective management of patients with heart failure exacerbation.It facilitates diagnosis,quantification of congestion,prognostication,and monitoring the efficacy of decongestive therapy.As such,it can effectively help to manage cardiorenal syndromes in various clinical settings.Extended or eVExUS explores additional veins,potentially broadening its applications.While VExUS demonstrates promising outcomes,challenges persist,particularly in cases involving renal and liver parenchymal disease,arrhythmias,and situations of pressure and volume overload overlap.Proficiency in utilizing spectral Doppler is pivotal for clinicians to effectively employ this tool.Hence,the integration of POCUS,especially advanced applications like VExUS,into routine clinical practice necessitates enhanced training across medical specialties.

Case Report: Carnitine Palmitoyl Transferase II (CPT II) Deficiency

Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.

Sound waves and solutions:Point-of-care ultrasonography for acute kidney injury in cirrhosis

This article delves into the intricate challenges of acute kidney injury(AKI)in cirrhosis,a condition fraught with high morbidity and mortality.The complexities arise from distinguishing between various causes of AKI,particularly hemodynamic AKI,in cirrhotic patients,who experience hemodynamic changes due to portal hypertension.The term"hepatocardiorenal syndrome"is introduced to encapsulate the intricate interplay among the liver,heart,and kidneys.The narrative emphasizes the often-overlooked aspect of cardiac function in AKI assessments in cirrhosis,unveiling the prevalence of cirrhotic cardiomyopathy marked by impaired diastolic function.The conventional empiric approach involving volume expansion and vasopressors for hepatorenal syndrome is critically analyzed,highlighting potential risks and variable patient responses.We advocate for a nuanced algorithm for AKI evaluation in cirrhosis,prominently featuring point-of-care ultrasonography(POCUS).POCUS applications encompass assessing fluid tolerance,detecting venous congestion,and evaluating cardiac function.

Point-of-care ultrasound in diagnosis and management of congestive nephropathy

Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examination,with findings such as jugular venous distension,a third heart sound,and vital signs as supporting findings.More recently,however,these once though objective measures have come under scrutiny for their accuracy.At the same time,bedside ultrasound has increased in popularity and is routinely being used by clinicians to take some of the guess work out of making the diagnosis of volume overload and venous congestion.In this mini-review,we will discuss some of the traditional methods used to measure venous congestion,describe the role of point-of-care ultrasound and how it can ameliorate a clinician’s evaluation,and offer a description of venous excess ultrasound score,a relatively novel scoring technique used to objectively quantify congestion.While there is a paucity of published large scale clinical trials evaluating the potential benefit of ultrasonography in venous congestion compared to gold standard invasive measurements,more study is underway to solidify the role of this objective measure in daily clinical practice.

Transcending boundaries:Unleashing the potential of multi-organ point-of-care ultrasound in acute kidney injury

Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid increase in serum creatinine levels or a decrease in urine output or both.In spite of thorough history-taking,physical examination,and laboratory analysis,there are limitations in the diagnostic process and clinical monitoring of AKI.Point-of-care ultrasonography(POCUS),a limited ultrasound study performed by clinicians at the bedside,has emerged as a valuable tool in different clinical settings.In this discussion,we explore the potential of POCUS performed by nephrologists to address specific questions encountered in the diagnosis and management of AKI patients.POCUS not only aids in excluding hydronephrosis but also provides real-time insights into hemodynamics,enabling formulation of individualized treatment plans.Further studies are required to assess the impact of multi-organ POCUS on pragmatic patient outcomes related to AKI,as well as its potential in risk stratification and identification of different levels of AKI severity and pathophysiological signatures.

Delivery Outcomes in Non-Tertiary Referral Centers for Women with Congenital Heart Disease

Background:Women with congenital heart disease(CHD)have increased risk for adverse events during pregnancy and delivery.Prior studies have assessed pregnancy and delivery outcomes at tertiary referral centers(TRC).The aim of our study was to assess pregnancy outcomes in women with CHD who deliver in a non-tertiary referral center(non-TRC).Methods:Clinical demographics were collected,including anatomic complexity,physiologic state and pre-pregnancy risk assessment.Patients were stratified by delivery location,either TRC or non-TRC.Maternal and neonatal complications of pregnancy were reported.Results:Women with CHD who delivered in a TRC had a higher pre-pregnancy risk when assessed by the Zahar and CARPREG-II scores,and had more patients fall into a higher WHO classification.There was no difference in rates of maternal cardiac complications between delivery locations(11%)and neonatal complications(20%)between deliveries at TRC and non-TRC.Conclusions:There were not increased maternal cardiac or neonatal complications when delivery occurred at a non-TRC.Neonatal complications remained high regardless of delivery location.This study suggests that proper risk assessment may help identify women who are candidates for safe delivery at non-TRC in women with CHD,and that neonatal resources should be considered when planning delivery location.

A Comprehensive View on the Progress of Organoid Research with an Emphasis on its Relevance to Disease Characterization

INTRODUCTION Organoids are primary tissue or stem cells derived cell aggregates that have the capacity for self-organization,self-renewal,and the capacity to mimic cellular and tissue level functions.Organoids can overcome the shortcomings of traditional 2D cell culture models and closely mimic 3D primary tissue composition.

Seeing through the myths:Practical aspects of diagnostic point-ofcare ultrasound in nephrology

Point of care ultrasonography(POCUS)is emerging as an invaluable tool for guiding patient care at the bedside,providing real-time diagnostic information to clinicians.Today,POCUS is recognized as the fifth pillar of bedside clinical examination,alongside inspection,palpation,percussion,and auscultation.In spite of growing interest,the adoption of diagnostic POCUS in nephrology remains limited,and comprehensive training beyond kidney ultrasound is offered in only a few fellowship programs.Moreover,several misconceptions and barriers surround the integration of POCUS into day-to-day nephrology practice.These include myths about its scope,utility,impact on patient outcomes and legal implications.In this minireview,we address some of these issues to encourage wider and proper utilization of POCUS.

Erratum:Rates of readmission and reoperation after operative management of midshaft clavicle fractures in adolescents

This is an erratum to an already published paper.We found an error in the results section and Table 1.Specifically,we have revised results with n≤10 to be reflected as such,which is consistent with the reporting instructions by the Agency for Healthcare Research and Quality.Please note,these changes do not affect our results,and we had previously listed this requirement in the results section.We apologize for our unintentional mistake.