Preclinical Experience Research Articles

Pre-clinical experiences among nursing students of reputable Islamic university in the capital city of Indonesia

Clinical trainings were employed in the nursing sciences in order to provide student’s experiences in applying nursing care according to the theory. They required to accomplish some competencies depending on their study levels. Students would also experience the possible barriers and challenge during clinical trainings. However, there were limited number of research which explored these experiences, especially in nursing students. This study aimed to explore the experiences of nursing students in performing fundamental nursing pre-clinical activities. This research conducted qualitative study with phenomenological approach. This study involved 5 nursing students according to inclusive criteria. Data collection method used in-depth interview techniques. The obtained data were analysed further using Colaizzi test. The collected data identified six themes of student’s experiences, such as student’s understanding about pre-clinic, their experiences during preclinic, theoretical gaps with hospital procedures, some barriers in clinical practice, student’s expectation, and obtained support during pre-clinic trainings. Pre-clinical trainings allowed nursing students to gain various medical experience and knowledge regarding nursing care. They could implement and compare the nursing theory with actual conditions in the hospital and society living. This topic needed to assess further about the benefits of pre-clinic trainings.

First-in-human cases and preclinical experience of a novel ICE catheter.

The primary objective of our study was to evaluate the first use of a novel intracardiac echocardiography (ICE) catheter in human subjects. This study aimed to assess its practicality, image clarity, and guidance role during electrophysiology procedures. Two patients underwent procedures using the novel ICE catheter. Post-procedure evaluations were conducted by four operators, who assessed the imaging quality and overall performance of the catheter. Anatomical and blood test results were also analyzed to determine the safety and impact on internal cardiac structures. Both patients were discharged one day after the procedure without any complications. The novel ICE catheter provided comparable imaging quality to existing commercial catheters. The catheter's advanced design allowed for detailed imaging at short distances, essential for accurate diagnosis and treatment planning. Moreover, it successfully navigated complex anatomical structures like the atrial septum and left atrial appendage. These preliminary studies indicate that the novel ICE catheter achieves a level of safety and effectiveness comparable to previously available commercial catheters. The findings highlight its potential to meet current clinical needs, particularly in sophisticated anatomic interventions. Despite the prolonged thrombin time after anticoagulant administration, both types of ICE catheters were non-damaging to cardiac structures during routine operations. The study underscores the importance of using trans-septal large inner diameter sheaths to minimize complications when advancing the catheter into the left atrium.

An Approach to Controlling Inflammation and Coagulation in Pig-to-Baboon Cardiac Xenotransplantation.

Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.

Creation of a resident-led medical student education committee.

The Resident-Student Education Committee (RSEC) is a novel approach to integrate and expand medical student education within an emergency medicine (EM) residency at a large academic center. There is a paucity of literature on such programs and there is no documentation of longitudinal initiatives with residents serving as specialty-specific advisors to students throughout medical school. The goals of creating the RSEC were to expand and improve the student educational experiences in EM, strengthen the connection between students and EM residents, and foster resident career development through sustainable leadership and teaching opportunities. The RSEC was composed of three divisions: the Preclinical Division aimed to increase student exposure to EM through didactics, skill sessions, simulation, and shadowing; the Clinical Division intended to enhance the student experience during clinical EM rotations through simulation and skill sessions and resident-student socials; and the Mentoring Division focused on advising students applying into EM through informational panels and one-on-one resident mentorship. Outcome measures include students applying into EM residency, which saw an increase from 8.9% prior to the RSEC's creation in 2020 to 12.9% in 2023, despite a national decline in EM applicants. Survey data also indicates favorable student preclinical experiences and improved confidence in clinical skills. The RSEC model, with its structured approach, resident leadership, and clear objectives, presents a sustainable and replicable framework for other residency programs seeking to enhance medical student education and promote resident engagement in teaching. Future directions include expanding shadowing opportunities and procedural skills teaching, introducing career mentorship earlier in the medical education timeline, and tracking outcomes data for continuous assessment and improvement.

Exploring Preclinical Medical Students' Experience Facilitating Group Dialectical Behavior Therapy (DBT) for a Student-Run Mental Health Clinic: A Qualitative Study.

This report explores the experiences of preclinical medical students who led group dialectical behavior therapy (DBT) for a student-run LGBTQ + mental health clinic. In the clinic, experienced clinicians trained and supervised preclinical medical students to facilitate DBT groups. The authors conducted a qualitative study to understand the impact of the DBT groups on the student facilitators via semi-structured interviews, which were evaluated using thematic analysis. The clinic hosted nine iterations of group DBT facilitated by preclinical medical students, involving 18 student leaders and 30 patients. Twelve student facilitators were interviewed. Participants had a diverse array of specialty interests and were primarily motivated by the opportunity for early clinical experience. They reported improved clinical skills, increased appreciation of psychotherapy as a treatment modality, and increased interest in incorporating psychotherapy in their future practice. Furthermore, participants reported using DBT skills to cultivate wellbeing during clerkship year and in their personal lives. Offering preclinical medical students the opportunity to lead group DBT therapy is a novel educational model providing early training in psychotherapy techniques. This opportunity for early direct patient experience in a supervised group setting attracted medical students with a diverse range of specialty interests. This model provided medical students specific DBT skills to implement in future patient care interactions and to maintain their personal wellbeing throughout medical training. The broad appeal and lasting effects of this program may prove beneficial at other institutions.

Creating a more equitable future: development, implementation, and evaluation of a novel surgical disparities curriculum for medical students

PurposeThe AAMC has expanded its focus on healthcare disparities training during undergraduate medical education (UME). Currently, no standardized published curriculum dedicated to surgical disparity training exists. Therefore, our purpose was to develop, implement, and evaluate a novel Surgical Disparities Curriculum to equip medical students to recognize peri-operative disparities.MethodsThe Surgical Disparities Curriculum was developed based on the Surgical Disparity Framework created by the NIH-American College of Surgeons Summit on Health Disparity using Kern’s Model of Curriculum Development. The curriculum includes four components which are illustrated in Fig. 1: (1) a pre-session review of a journal article and multimedia adjunct highlighting one category within the framework, (2) a didactic session highlighting key elements of the state of surgical disparities and teaching the NIH-ACS framework, (3) a review of a clinical vignette and articles highlighting a framework factor, and (4) a discussion session applying all elements of the framework to disparities identified in pre-session materials, clinical vignette, and personal clinical experiences. The curriculum was administered at a single large academic institution to 223 third-year medical students. Curriculum evaluation was performed using Kirkpatrick’s Model of Training Evaluation and included post-participation surveys to evaluate participant reaction to the curriculum as well as pre- and post-course assessments to evaluate learning. Results were pooled and a Fisher’s exact test or independent samples t test was used for relevant analysis with p < 0.05 considered significant. Thematic analysis, using common word groupings, was also performed on post-survey comments.Fig. 1Outline of novel Surgical Disparities Curriculum for Medical Students. Pre-session preparation includes a survey and a guided reading with a relevant journal article and a multimedia adjunct. Next is a didactic session that introduces a Surgical Disparities Framework established by the ACS in 2016 and gives students a background in the language of discussing disparities. Next is a clinical vignette that highlights a framework factor and several disparities of interest. This is followed by a guided discussion on the pre-session materials, the didactic component, and the clinical vignette within the framework accompanied by a discussion on how to apply the framework and identify and prevent disparities. This was followed by a post-session surveyResultsParticipants stated they had prior dedicated training in recognizing health disparities integrated throughout the UME curriculum during pre-clinical (83%) and clinical (89%) experiences. Only 31% of students agreed surgical disparities had been discussed during their rotation prior to curriculum implementation. After curriculum participation, 90% of students endorsed an improved understanding of surgical disparities in healthcare and there was a 20% improvement in self-reported identification of peri-operative disparities from 68 to 88% (20% [CI 12–28%], p < 0.0001). Participation in the curriculum also resulted in knowledge acquisition with students scoring better (78% v 59% at baseline; p < 0.0001) on post-participation assessment.ConclusionThe Surgical Disparities Curriculum provides a novel solution for bridging the gap in training medical students to recognize disparities in the care of surgical patients. Future work will be done to assess long-term retention and behavioral changes because of our intervention. In addition, we will be working on the translatability of our curriculum to other institutions with the goal of training clerkship students across the country to better recognize surgical disparities.

Exploring monocarboxylate transporter inhibition for cancer treatment.

Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.

Frontlines and Crossroads: The Impact of COVID-19 on the Motivations of Medical Students from Selected Philippine Medical Schools in Pursuing Their Medical Studies

BACKGROUND: The onset of the COVID-19 pandemic made changes to the Philippine medical education system to transfer to an online setting, which meant the loss of practical skills needed for future clinical encounters. Most students consider the desire to serve others as their motivation to pursue medicine, but stated that online learning was more favorable for theoretical lessons and not for practical skills. These students had to cope with lifestyle changes which challenged their resolve, as well as deal with the technology and infrastructure required for online learning. The study aimed to compare the strength and nature of motivations of medical students to pursue their studies before and after the onset of the pandemic, and to propose recommendations to support them through the pandemic and beyond. METHODS: Semi-structured interviews were conducted using a study questionnaire that dealt with determining respondents’ motivations for pursuing a medical degree, the impact of the pandemic and how it may have changed their motivations, and what recommendations they can propose to motivate other medical students. Interview transcripts were then analyzed through a qualitative inductive thematic analysis. Pre-clinical and clinical students (clerks and postgraduate interns) enrolled during SY 2020-2021 from Metro Manila and from among the 3 major Philippine island groups were selected to approximate the distribution of medical schools across the country. A total of 17 eligible participants were selected through purposive sampling of different personal backgrounds. Recruitment and call for participants were coursed through the Association of Philippine Medical Colleges - Student Network as well as through social media. Data from interview transcripts were familiarized and ideas from important recurring patterns shared among respondents’ answers were made into codes, which were subsequently organized into themes both unique and generalizable across student groups. RESULTS: Six major themes arose: 1) Contextualizing the pre-clinical and clinical experiences, 2) Challenges of online learning; 3) Desire for lived experience; 4) Tensions between personal contexts and online learning; 5) Grit driven by a desire to serve; 6) Resilience over adversity and sunk cost. Most pre-clinical students were motivated to pursue medicine by a desire to serve, while clinical students were straightforward about financial reward as motivation. Despite the limitations of online education, lack of social interaction and skills training, medical students had strengthened motivations to continue their studies as the pandemic highlighted the need for physicians, reinforcing their intrinsic desire to serve others. Mental health and financial issues were a concern for some, but these students did not wish to quit so as not to lose momentum with their studies. CONCLUSION: While most medical students interviewed felt more motivated in pursuing their studies during the pandemic, there was a desire and a call for more support in their studies and training. Their personal stories suggested there is room for improvement in certain aspects of local medical education. Addressing their concerns through financial and educational support, and bridging clinical skills with online learning would thus help them create quality healthcare in the pandemic context and beyond.

Preclinical experience using 4-dimensional intracardiac echocardiography with CARTO integration

Preclinical experience using 4-dimensional intracardiac echocardiography with CARTO integration

Twelve tips for creating a longitudinal quality improvement and safety education for early health professions students

Despite the numerous calls for integrating quality improvement and patient safety (QIPS) curricula into health professions education, there are limited examples of effective implementation for early learners. Typically, pre-clinical QIPS experiences involve lectures or lessons that are disconnected from the practice of medicine. Consequently, students often prioritize other content they consider more important. As a result, they may enter clinical settings without essential QIPS skills and struggle to incorporate these concepts into their early professional identity formation. In this paper, we present twelve tips aimed at assisting educators in developing QIPS education early in the curricula of health professions students. These tips address various key issues, including aligning incentives, providing longitudinal experiences, incorporating real-world care outcomes, optimizing learning environments, communicating successes, and continually enhancing education and care delivery processes.

The KIDNEE Club: An Acceptability and Feasibility Study of a Preclinical Medical Student Experience in a Pediatric Dialysis Unit Pilot Program

The KIDNEE Club: An Acceptability and Feasibility Study of a Preclinical Medical Student Experience in a Pediatric Dialysis Unit Pilot Program

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant.

Human urinary bladder transplantation has never been performed. From a technical standpoint, challenges include the complex deep pelvic vascular anatomy, limited intraoperative visualization, and high procedural complexity. In preparation for a first-in-human clinical trial, we report preclinical studies to develop the technique of robotic retrieval and autotransplantation of vascularized composite bladder allograft. Institutional Animal Care and Use Committee, Institutional Review Board, and UNOS (United Network for Organ Sharing) approvals were obtained, and IDEAL (Idea, Development, Exploration, Assessment, Long-term Study) Reporting Guidelines were followed. Robotic vascularized composite bladder allograft recovery, back-table graft preparation, and robotic autotransplantation were performed in 3 vascularized model settings: living porcine (n=3), pulsatile human cadavers (n=2), and heart-beating brain-dead deceased research human donors (n=5). Our primary objective was to develop a reproducible technique for robotic vascularized composite bladder allograft transplantation. Technical success was defined by adequate, sustained vascularized composite bladder allograft reperfusion. Secondary objectives were intraoperative parameters, including operative time, graft ischemia time, and blood loss. Successful robotic vascularized composite bladder allograft autotransplantation was achieved in 2 porcine, 1 cadaver, and 3 brain-dead research donors. In the heart-beating research donors, console time decreased with successive surgeries, and visual inspection revealed healthy revascularized autografts with prompt, global indocyanine green immunofluorescence uptake. In 1 heart-beating donor who was hemodynamically maintained for 12 hours postoperatively, reinspection confirmed excellent maintained global vascularized composite bladder allograft vascularity and bladder mucosal integrity. To our knowledge, the first preclinical experience of bladder autotransplantation in vascularized models is reported, including robotic vascularized composite bladder allograft recovery, back-table reconstruction, and autotransplantation. This experience represents the essential preclinical work required to build toward the first-in-human trial of bladder transplantation, performed under a UNOS-approved genitourinary vascularized composite bladder allograft program (NCT No. 05462561).

A Qualitative Analysis of Experiences of Medical Students Serving as Abortion Doulas.

Innovative strategies are needed in clinical education to teach empathetic behavior and communication skills. This study aimed to investigate preclinical medical students' experiences volunteering as abortion doulas and to understand the impact of their participation on their professional training. In this qualitative study, the authors conducted semistructured interviews with medical students who had volunteered as abortion doulas in March to July 2016. The interviews described motivations for participating, experiences volunteering as a doula, approach to caring for patients, and acquisition of communication skills and knowledge of abortion. The authors analyzed interview transcripts using a conventional content analysis approach, and themes were identified. The authors performed 22 interviews. For most participants, this was their first exposure to an abortion procedure or patient care in any capacity. Participants identified acquisition of skills including patient advocacy, communication, and empathy that they were later able to apply throughout their clinical clerkships. This opportunity improved well-being and solidified their decision to apply for residencies in reproductive health fields. After volunteering as abortion doulas, medical students were able to develop communication skills, empathy, and patient advocacy applicable to other areas of patient care. Preclinical students, potentially in other health care professions training, participating in patient care as doulas have the potential to further personal development, professionalism, and activism.

Abortion education: What are future physicians learning in medical school?

ObjectivesThe last nationwide evaluation of abortion education in undergraduate medical schools was conducted by Espey et al. more than 15 years ago. To better understand what medical schools are teaching medical students about abortion care, we conducted a brief assessment of abortion education and training at U.S. medical schools. Study designIn April 2019, the study team emailed a three-item survey to the obstetrics and gynecology clerkship directors at Association of American Medical Colleges-accredited U.S. allopathic medical schools (n = 143). The multiple-choice survey assessed the availability and type of reproductive health education students had during their preclinical and clinical experiences. ResultsNinety-one (64%) medical schools responded. Fifty-four (59%) schools reported abortion education as part of their preclinical curriculum, with 26 (29%) dedicating at least one lecture to abortion education. Sixty-seven (74%) institutions provided a clinical abortion experience for students, with 24 (26%) indicating students had to arrange participation on their own. Nine programs (10%) reported offering no formal abortion education. ConclusionsWhile the availability of abortion education has increased since the last nationwide survey in 2005, discrepancies in the education offered persist, and many medical students remain without access to this training. ImplicationsAlthough abortion plays an essential role in women’s health services, discrepancies in training opportunities limit abortion education in U.S. medical schools. Gaps in the education of medical students may have downstream effects on the availability of doctors who are trained in providing medically-safe abortions.

TAM family kinases as therapeutic targets at the interface of cancer and immunity.

Novel treatment approaches are needed to overcome innate and acquired mechanisms of resistance to current anticancer therapies in cancer cells and the tumour immune microenvironment. The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) are potential therapeutic targets in a wide range of cancers. In cancer cells, TAM RTKs activate signalling pathways that promote cell survival, metastasis and resistance to a variety of chemotherapeutic agents and targeted therapies. TAM RTKs also function in innate immune cells, contributing to various mechanisms that suppress antitumour immunity and promote resistance to immune-checkpoint inhibitors. Therefore, TAM antagonists provide an unprecedented opportunity for both direct and immune-mediated therapeutic activity provided by inhibition of a single target, and are likely to be particularly effective when used in combination with other cancer therapies. To exploit this potential, a variety of agents have been designed to selectively target TAM RTKs, many of which have now entered clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians, including an overview of the rationale for therapeutic targeting of TAM RTKs in cancer cells and the tumour immune microenvironment, a description of the current preclinical and clinical experience with TAM inhibitors, and a perspective on strategies for continued development of TAM-targeted agents for oncology applications.

NGR-Based Radiopharmaceuticals for Angiogenesis Imaging: A Preclinical Review.

Angiogenesis plays a crucial role in tumour progression and metastatic spread; therefore, the development of specific vectors targeting angiogenesis has attracted the attention of several researchers. Since angiogenesis-associated aminopeptidase N (APN/CD13) is highly expressed on the surface of activated endothelial cells of new blood vessels and a wide range of tumour cells, it holds great promise for imaging and therapy in the field of cancer medicine. The selective binding capability of asparagine-glycine-arginine (NGR) motif containing molecules to APN/CD13 makes radiolabelled NGR peptides promising radiopharmaceuticals for the non-invasive, real-time imaging of APN/CD13 overexpressing malignancies at the molecular level. Preclinical small animal model systems are major keystones for the evaluation of the in vivo imaging behaviour of radiolabelled NGR derivatives. Based on existing literature data, several positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radioisotopes have been applied so far for the labelling of tumour vasculature homing NGR sequences such as Gallium-68 (68Ga), Copper-64 (64Cu), Technetium-99m (99mTc), Lutetium-177 (177Lu), Rhenium-188 (188Re), or Bismuth-213 (213Bi). Herein, a comprehensive overview is provided of the recent preclinical experiences with radiolabelled imaging probes targeting angiogenesis.

Preclinical Immersion Experiences Improve Medical Student Perceptions of Surgery

IntroductionMedical students historically receive little to no preclinical exposure to surgery and surgical subspecialties. As a result, by the time they reach their clinical clerkship time, students often have already found interest in other specialties. The goal of this study is to utilize the knowledge to action (KTA) implementation framework to design and refine a clinical immersion experience during the second year of medical school. MethodsA total of 94 second-year Harvard Medical School students underwent the surgical immersion experience between 2019 and 2022 (the program was postponed in 2020 due to COVID). The development and refinement of the curriculum were nicely modeled by the KTA implementation framework. We identified a gap in medical student preclinical education, adapted a curriculum for preclinical medical students at Massachusetts General Hospital , selected the curriculum components to provide a high-level overview of surgery, monitored the student experience, and evaluated outcomes using the student surveys. Based on the survey results, inductive thematic analysis was utilized to identify prominent positive and negative themes. The feedback was then used to tailor subsequent iterations of the immersion experience. ResultsEighty-eight medical students completed the survey (RR = 93.6%), and 85% rated the immersion experience as “excellent”, 11% “very good”, 4% “good”, and 0% “fair” or “poor”. There was no significant difference in ratings between sessions. Several key themes were identified, including changed perceptions, diversity of surgical fields, teamwork, surgery clerkship preparedness, and the need for more preclinical exposure. ConclusionsPreclinical medical students gave overwhelmingly positive reviews of the surgical immersion experience. A half-day intervention is sufficient to begin changing students’ views toward surgery, disproving stereotypes, and even inspiring some to consider a surgical field themselves. In addition, the KTA implementation framework is a useful model for the development and refinement of medical education curricula.

#5187 GREASE II: A PHASE II RANDOMIZED, 24-MONTH, PARALLEL-GROUP, SUPERIORITY STUDY TO EVALUATE THE EFFICACY OF A KETOGENIC DIET IN ADPKD PATIENTS

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the 4th cause of end-stage renal disease in Western Countries, nevertheless still represents an illness with a significant unmet medical need. In recent years, deregulation in glucose metabolism in ADPKD has been identified. Data suggest that cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis. Preclinical experiences show beneficial effects in terms of cystic size reduction, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. A ketogenic diet treatment approach, such as a Modified Atkins Diet (MAD), to ADPKD represents an interesting therapeutic strategy, because of its low cost, tolerability and safety [1]. The Primary Endpoint of this study is the evaluation of the effect of the MAD protocol on the modification of the Total Kidney Volume (TKV), formally qualified, both by FDA and by EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline. Method the initial protocol [2] has been modified in a multicentric study that involves the Divisions of Nephrology of AOU Policlinico di Modena (Modena, Italy) and Policlinico di Sant'Orsola (Bologna, Italy). GREASE II is supported by the Italian Ministry of Health (Ricerca Finalizzata grant no. RF-2021-12374522). During the run-in period, 90 patients will follow a Balanced Normocaloric Diet (BND). In the week preceding the randomization, patients will perform a baseline MRI. Patients will be then randomized to MAD or BND according to a stratified 1:1 ratio. Patients will be followed for 12 months at scheduled clinical and dietetic visits. In the 12ve month, the patients on the MAD arm will be switched to BND and a second MRI will be performed after a month (± 7 days). After the MRI, the patients will be switched again to their original MAD. Patients will be followed for further 12 months at scheduled clinical and dietetic visits. At the 24th month, patients of the MAD arm will be switched once again to BND and after a month (± 7 days) a final visit will be performed (Fig. 1). As co-primary endpoint tolerability and safety will be assessed. Furthermore, as secondary outcomes, the study will evaluate renal function decline, total liver volume (TLV) and the impact of the diets on urinary and serum markers β2MG and MCP-1. Results we expect to obtain a reduction of the TKV in the group of patients treated by the MAD protocol. Safety and tolerability are coprimary endpoints of the study. As secondary exploratory outcomes, the study will evaluate the effect of the diet on the TLV and quality of life (ADPKD-IS and SF-12 questionnaires). This clinical trial will allow us to evaluate the proof of concept of the therapeutic efficacy of MAD in the ADPKD clinical setting. Conclusion GREASE II represents the first multicenter RCT evaluating the reduction of the TKV in ADPKD and renal function decline. The identification of a coordinated reduction of TKV and renal function decline in the patients randomized to the MAD compared to the BND will suggest a protective role of the ketogenic diet against disease progression of ADPKD.

Fertility, teratogenicity, and contraception during therapy with BRAF/MEK inhibitors

Targeted mutation-based therapy with BRAF and MEK inhibitors has become an integral part of systemic therapy for metastatic melanoma in the advanced setting and for the adjuvant therapy of melanoma in stageIII after complete resection. Due to the increased chances of survival and early use in the adjuvant situation, fertility preservation as well as aspects of teratogenicity and pregnancy are increasingly relevant in patients who are often still young. To communicate the published and study-based information on fertility preservation, teratogenicity and pregnancy under therapy with BRAF and MEK inhibitors. Summaries of product characteristics as well as studies and case reports on BRAF and MEK inhibitors published in PubMed were used as sources of information. There are no specific preclinical studies or experience in humans on fertility, teratogenicity, and contraception with targeted therapy. Recommendations can only be derived from toxicity studies and individual case reports. Patients should be offered counseling on the options for fertility-protective measures before starting targeted therapy. Due to unclear teratogenicity, adjuvant melanoma therapy with dabrafenib and trametinib should not be initiated in pregnant patients. In the advanced metastatic situation, BRAF and MEK inhibitors should only be given after extensive interdisciplinary education and counselling of the pregnant patient and her partner. Patients should be informed about the need for adequate contraception during targeted therapy.

The new era of anticoagulation: factor XI and XII inhibitors

The two last decades have witnessed a revolution in the field of anticoagulation, mainly due to the advent of direct anticoagulant with targeted action against single coagulation proteins. However, the residual risk of cardio- and cerebrovascular events, particularly in some critical settings, and the risk of major bleeding still represent unmet medical needs. Preclinical studies and experience from families with genetic deficiencies of factor XI or XII (FXI and FXII) allowed to identify these factors involved in the contact pathway of coagulation as potential targets for new anticoagulant approaches. To date, several pharmacological classes of FXI and FXII inhibitors have been developed, including antisense oligonucleotides, monoclonal antibodies, small molecules, natural inhibitors, and aptamers, and various molecules are currently under phase 2 or 3 clinical investigation. Particularly, promising results have been obtained in patients undergoing major orthopedic surgery, in those with end-stage kidney disease, atrial fibrillation and acute coronary syndrome. This review summarizes current knowledge on FXI and FXII inhibitors, with a particular focus on their pharmacological properties and potential clinical indications.