Breaking bad news: an active learning method for medical students.

BACKGROUND: Breaking bad news is one of the most difficult aspects of communication in medicine. The objective of this study was to assess the relevance of a novel active learning course on breaking bad news for fifth-year students. METHODS: Students were divided into two groups: Group 1, the intervention group, participated in a multidisciplinary formative discussion workshop on breaking bad news with videos, discussions with a pluri-professional team, and concluding with the development of a guide on good practice in breaking bad news through collective intelligence; Group 2, the control group, received no additional training besides conventional university course. The relevance of discussion-group-based active training was assessed in a summative objective structured clinical examination (OSCE) station particularly through the students' communication skills. RESULTS: Thirty-one students were included: 17 in Group 1 and 14 in Group 2. The mean (range) score in the OSCE was significantly higher in Group 1 than in Group 2 (10.49 out of 15 (7; 13) vs. 7.80 (4.75; 12.5), respectively; p = 0.0007). The proportion of students assessed by the evaluator to have received additional training in breaking bad news was 88.2% (15 of the 17) in Group 1 and 21.4% (3 of the 14) in Group 2 (p = 0.001). The intergroup differences in the Rosenberg Self-Esteem Scale and Jefferson Scale of Empathy scores were not significant, and both scores were not correlated with the students' self-assessed score for success in the OSCE. CONCLUSION: Compared to the conventional course, this new active learning method for breaking bad news was associated with a significantly higher score in a summative OSCE. A longer-term validation study is needed to confirm these exploratory data.

Prenatal Sonographic Features of Rubinstein-Taybi Syndrome-A Small Case Series of a Rare Syndrome.

Rubinstein-Taybi syndrome (RSTS) is a rare syndrome characterized by intellectual disability, distinctive facial features and distal limb abnormalities. RSTS is indicated by clinical features and confirmed via genetic testing. In this prenatal case series, we report four cases of RSTS with various sonographic features. Some features, such as corpus callosum dysgenesis, are nonspecific, but they may be the first sign apparent, as they appear early in pregnancy. Others, like beaked nose, shawl scrotum, premature coccygeal ossification, and overly mature scrotal sac with excessive rugae, are distinctive, but they may only be apparent in advanced gestation.

Postnatal outcome following fetal aortic valvuloplasty for critical aortic stenosis.

OBJECTIVE: To report our experience of fetal aortic valvuloplasty (FAV) for critical aortic stenosis (AS), with a focus on the postnatal evolution of the patients. METHODS: This was a retrospective study including all fetuses with critical AS which underwent FAV in a single center between January 2011 and June 2022. FAV was performed under ultrasound guidance. Technical success was based upon balloon inflation across the aortic valve and improvement of the antegrade aortic flow across the aortic valve. At birth, a biventricular circulation (BVC) strategy was decided assuming the left ventricular (LV) systolic and diastolic function would ensure the systemic circulation. RESULTS: Sixty-three FAV procedures were performed in 58 fetuses, at a median (range) gestational age of 26.2 (20.3-32.2) weeks. The procedure was technically successful in 50/58 (86.2%) fetuses. There were 11/58 (19.0%) cases of in-utero demise and 9/58 (15.5%) terminations of pregnancy. No patient was liveborn after an unsuccessful procedure. Thirty-eight (65.5%) infants were liveborn, at a median (range) gestational age of 38.1 (29.0-40.6) weeks, of whom 21 (55.3%) required prostaglandin treatment. Twenty-eight of the 38 (73.7%) liveborn children (48.3% of the study population) entered the BVC pathway at birth. Among them, 20 (71.4%) required an aortic valvuloplasty procedure at birth (11 (55.0%) percutaneous balloon, nine (45.0%) surgical) and eight (28.6%) did not require any treatment at birth, but, of these, five (62.5%) underwent surgical valvuloplasty between day 26 and day 1200 of age. Eleven (39.3%) of the infants with BVC at birth required a second intervention and four (14.3%) of them required a third intervention. Two (7.1%) infants who entered the BVC pathway at birth underwent conversion to univentricular circulation (UVC). None of the surviving children with BVC developed pulmonary hypertension. The overall survival rate in those with BVC at birth was 22/28 (78.6%) at a median (range) follow-up of 23.3 (2.0-112.6) months. Ten of the 58 (17.2%) patients had UVC at birth. Among these, six (60.0%) received compassionate care from birth and four (40.0%) underwent surgery. Three of the 10 patients who had UVC at birth were still alive at the latest follow-up assessment, at a median (range) gestational age of 24.3 (8.3-48.7) months. CONCLUSIONS: FAV for critical AS led to increase of antegrade aortic flow in 86.2% of fetuses, with BVC being achieved in 48.3% (73.7% of the liveborn cases). Among patients with BVC at birth, the rate of reintervention was high, but 78.6% of these children were alive at the latest evaluation. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

New N-aryl-N-alkyl-thiophene-2-carboxamide compound enhances intracellular Ca2+ dynamics by increasing SERCA2a Ca2+ pumping.

The type 2a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) plays a central role in the intracellular Ca2+ homeostasis of cardiac myocytes, pumping Ca2+ from the cytoplasm into the sarcoplasmic reticulum (SR) lumen to maintain relaxation (diastole) and prepare for contraction (systole). Diminished SERCA2a function has been reported in several pathological conditions, including heart failure. Therefore, development of new drugs that improve SERCA2a Ca2+ transport is of great clinical significance. In this study, we characterized the effect of a recently identified N-aryl-N-alkyl-thiophene-2-carboxamide (or compound 1) on SERCA2a Ca2+-ATPase and Ca2+ transport activities in cardiac SR vesicles, and on Ca2+ regulation in a HEK293 cell expression system and in mouse ventricular myocytes. We found that compound 1 enhances SERCA2a Ca2+-ATPase and Ca2+ transport in SR vesicles. Fluorescence lifetime measurements of fluorescence resonance energy transfer between SERCA2a and phospholamban indicated that compound 1 interacts with the SERCA-phospholamban complex. Measurement of endoplasmic reticulum Ca2+ dynamics in HEK293 cells expressing human SERCA2a showed that compound 1 increases endoplasmic reticulum Ca2+ load by enhancing SERCA2a-mediated Ca2+ transport. Analysis of cytosolic Ca2+ dynamics in mouse ventricular myocytes revealed that compound 1 increases the action potential-induced Ca2+ transients and SR Ca2+ load, with negligible effects on L-type Ca2+ channels and Na+/Ca2+ exchanger. However, during adrenergic receptor activation, compound 1 did not further increase Ca2+ transients and SR Ca2+ load, but it decreased the propensity toward Ca2+ waves. Suggestive of concurrent desirable effects of compound 1 on RyR2, [3H]-ryanodine binding to cardiac SR vesicles shows a small decrease in nM Ca2+ and a small increase in µM Ca2+. Accordingly, compound 1 slightly decreased Ca2+ sparks in permeabilized myocytes. Thus, this novel compound shows promising characteristics to improve intracellular Ca2+ dynamics in cardiomyocytes that exhibit reduced SERCA2a Ca2+ uptake, as found in failing hearts.

Can the Hartree-Fock kinetic energy exceed the exact kinetic energy?

The Hartree-Fock (HF) approximation has been an important tool for quantum-chemical calculations since its earliest appearance in the late 1920s and remains the starting point of most single-reference methods in use today. Intuition suggests that the HF kinetic energy should not exceed the exact kinetic energy; but no proof of this conjecture exists, despite a near century of development. Beginning from a generalized virial theorem derived from scaling considerations, we derive a general expression for the kinetic energy difference that applies to all systems. For any atom or ion, this trivially reduces to the well-known result that the total energy is the negative of the kinetic energy and, since correlation energies are never positive, proves the conjecture in this case. Similar considerations apply to molecules at their equilibrium bond lengths. We use highly precise calculations on Hooke's atom (two electrons in a parabolic well) to test the conjecture in a nontrivial case and to parameterize the difference between density functional and HF quantities, but find no violations of the conjecture.

Accuracy and impact of prenatal diagnosis of common arterial trunk.

OBJECTIVES: Outcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The main objective of this study was to evaluate the accuracy of prenatal diagnosis of CAT by analyzing prenatal vs postnatal assessment of: (1) anatomic subtypes and (2) truncal valve function. The secondary objective was to assess the potential impact of prenatal diagnosis of CAT on postnatal mortality and morbidity by comparing prenatally vs postnatally diagnosed patients. METHODS: This was a retrospective analysis of all CAT patients diagnosed either prenatally, with postnatal or fetopsy confirmation, or postnatally, from 2011 to 2019 in a single tertiary center. Cohen's kappa statistic was used to evaluate agreement between pre- and postnatal assessment of anatomic subtypes according to Van Praagh and of truncal valve function. Mortality and morbidity variables were compared between prenatally vs postnatally diagnosed CAT patients. RESULTS: A total of 84 patients (62 liveborn with prenatal diagnosis, 16 liveborn with postnatal diagnosis and six terminations of pregnancy with fetopsy) met the inclusion criteria. The accuracy of prenatal diagnosis of CAT anatomic subtype was 80.3%, and prenatal and postnatal concordance for subtype diagnosis was only moderate (κ = 0.43), with no patient with CAT Type A3 (0/4) and only half of patients with CAT Type A4 (8/17) being diagnosed prenatally. Fetal evaluation of truncal valve function underestimated the presence (no agreement; κ = 0.09) and severity (slight agreement; κ = 0.19) of insufficiency. However, four of five cases of postnatally confirmed significant truncal valve stenosis were diagnosed prenatally, with fair agreement for both presence and severity of stenosis (κ = 0.38 and 0.24, respectively). Mortality was comparable in patients with and those without prenatal diagnosis (log-rank P = 0.87). CAT patients with fetal diagnosis underwent earlier intervention (P < 0.001), had shorter intubation time (P = 0.047) and shorter global hospital stay (P = 0.01). CONCLUSIONS: The accuracy of prenatal diagnosis of CAT is insufficient to tailor neonatal management and to predict outcome. Fetal assessment of truncal valve dysfunction appears unreliable due to perinatal transition. Improvement is necessary in the fetal diagnosis of anatomic subtypes of CAT requiring postnatal prostaglandin infusion. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiac ryanodine receptor N-terminal region biosensors identify novel inhibitors via FRET-based high-throughput screening.

The N-terminal region (NTR) of ryanodine receptor (RyR) channels is critical for the regulation of Ca2+ release during excitation-contraction (EC) coupling in muscle. The NTR hosts numerous mutations linked to skeletal (RyR1) and cardiac (RyR2) myopathies, highlighting its potential as a therapeutic target. Here, we constructed two biosensors by labeling the mouse RyR2 NTR at domains A, B, and C with FRET pairs. Using fluorescence lifetime (FLT) detection of intramolecular FRET signal, we developed high-throughput screening (HTS) assays with these biosensors to identify small-molecule RyR modulators. We then screened a small validation library and identified several hits. Hits with saturable FRET dose-response profiles and previously unreported effects on RyR were further tested using [3H]ryanodine binding to isolated sarcoplasmic reticulum vesicles to determine effects on intact RyR opening in its natural membrane. We identified three novel inhibitors of both RyR1 and RyR2 and two RyR1-selective inhibitors effective at nanomolar Ca2+. Two of these hits activated RyR1 only at micromolar Ca2+, highlighting them as potential enhancers of excitation-contraction coupling. To determine whether such hits can inhibit RyR leak in muscle, we further focused on one, an FDA-approved natural antibiotic, fusidic acid (FA). In skinned skeletal myofibers and permeabilized cardiomyocytes, FA inhibited RyR leak with no detrimental effect on skeletal myofiber excitation-contraction coupling. However, in intact cardiomyocytes, FA induced arrhythmogenic Ca2+ transients, a cautionary observation for a compound with an otherwise solid safety record. These results indicate that HTS campaigns using the NTR biosensor can identify compounds with therapeutic potential.

Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastases from colorectal cancer in the Czech Republic in 2018.

BACKGROUND: For highly selected patients with peritoneal metastases (PM) from colorectal cancer (CRC), an aggressive surgical approach with intraperitoneal chemotherapy may be beneficial. This management may prolong overall survival, which is well documented by the results of a number of clinical trials. In the Czech Republic, five specialized centers of surgical oncology are able to perform cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC). All of these centers provided accurate information on the number of CRS procedures in 2018 in the PM CRC indication. The estimation of the prevalence of peritoneal metastases from CRC is based on data from the Czech National Cancer Registry. PURPOSE: To determine the number of cytoreductive procedures performed in patients with peritoneal metastases from CRC in the Czech Republic in 2018, and to compare it with the number of patients who could hypothetically benefit from this procedure according to statistical data. RESULTS: Twenty-five CRS/HIPEC procedures were performed on patients with peritoneal metastases from CRC in 2018 in the Czech Republic. However, based on the prevalence of peritoneal metastases from CRC in the Czech Republic, cytoreduction with intraperitoneal chemotherapy (CRS/HIPEC) could probably bring benefit to a minimum of 150 patients a year in the Czech Republic. CONCLUSION: In the Czech Republic in 2018, the cytoreduction and HIPEC procedures for peritoneal metastases from CRC were performed in significantly fewer cases than would correspond to the estimated number of potentially curable patients.To increase the awareness of this issue and improve the number of potentially curative cytoreductive procedures, there will be necessary better awareness and closer cooperation among specialized centers, general surgeons, and clinical oncologists.

Impact of volume, immunoglobulin G concentration, and feeding method of colostrum product on neonatal nursing behavior and transfer of passive immunity in beef calves.

One-third of beef calves fail to achieve adequate transfer of passive immunity (TPI) through timely ingestion of colostrum, which substantially increases their risk of preweaning morbidity and mortality. Two randomized clinical trials were designed to assess the impact of volume, immunoglobulin G (IgG) concentration, and feeding method of colostrum product on neonatal nursing behavior and TPI. In Trial 1, 47 calves were randomly assigned to receive one of three colostrum interventions by oro-esophageal tube feeder (OET): 1 L with 100 g/L IgG, 1.4 L with 70 g/L IgG, or 2 L with 100 g/L IgG. In Trial 2, 29 calves were randomly assigned to be fed 1 L of colostrum product with 100 g/L IgG by either nipple bottle (NB) or OET. Colostrum intervention (i.e. feeding of colostrum product) occurred within 60 minutes of birth. Cow-calf pairs were monitored by video surveillance in individual stalls for 24 h. Dam colostrum was collected at 10 minutes and calf serum was collected at 24-36 h after birth to assess IgG concentration. Differences among colostrum intervention groups on latency to stand and nurse were analyzed using Kaplan-Meier survival curves and Cox proportional hazard models. The impact of colostrum intervention group on TPI was assessed using multivariable linear regression modeling. In Trial 1, calves fed 1.4 L with 70 g/L IgG by OET nursed from their dams statistically significantly earlier compared to calves fed 1 L with 100 g/L IgG (P = 0.003) and calves fed 2 L with 100 g/L IgG (P = 0.008). Six of the 15 calves in the NB group in Trial 2 refused to consume part of the colostrum feeding offered by bottle and required follow-up tube feeding of the remaining volume. These calves were analyzed as a separate group (NB + OET). Calves fed 1 L by NB stood and nursed statistically significantly earlier than calves fed by OET (P = 0.005) or a combination of NB + OET (P = 0.003). Calf serum IgG concentrations were not statistically significantly different among colostrum intervention groups (P > 0.1). Overall, the colostrum interventions assessed in this study led to only one calf with failed TPI. While statistically significant differences in serum IgG concentrations were not detected in this study, subsequent nursing behavior did vary and was improved by feeding a moderate volume (1.4 L with 70 g/L IgG) of colostrum when using an OET, and by using the NB when feeding a smaller volume (1 L with 100 g/L IgG).

Multifactorial origin of pulmonary hypertension in a child with congenital heart disease, Down syndrome, and BMPR-2 mutation.

A late preterm infant had pulmonary hypertension caused by a variety of mechanisms leading to complex management. This child had complete atrioventricular septal defect associated with mild left ventricular hypoplasia and Down syndrome diagnosed prenatally. The mother had been treated by antiretroviral HIV treatment during pregnancy. Aortic coarctation was diagnosed and rapidly repaired. After surgery, he required noninvasive ventilation for persisting elevated PCO2. Pulmonary CT scan showed normal bronchial tree, lung parenchymal abnormalities with mosaic aspect and hyperlucent zones, and indirect signs of lung hypoplasia with peripheral microbubbles. During follow-up, severe pulmonary hypertension was diagnosed on echocardiography without recoarctation, significant intracardiac shunting or diastolic dysfunction. The patient died after four months unable to be weaned from noninvasive ventilation. Post mortem lung biopsy showed abnormally muscularized arterioles with intimal fibrosis and pulmonary immaturity. Gentetic screening identified a BMPR-2 mutation. This patient illustrates the multifactorial origin of pulmonary hypertension in the neonatal period. The respective contribution of left-to-right shunt, post-capillary obstruction, and abnormally elevated pulmonary vascular resistances led to perform right heart catheterization to exclude excessive shunting and restrictive physiology of the left heart. Subjects with Down syndrome are also highly susceptible to decreased lung vascular and alveolar growth, which may increase the risk for pulmonary hypertension and lung hypoplasia. This case highlights two issues. The first one is that right heart catheterization should be discussed in neonates with unexplained pulmonary hypertension and the second is to extend indications of genetic testing for pulmonary hypertension genes in neonates who have unusual course of neonatal pulmonary hypertension, particularly in the setting of associated congenital heart disease (CHD).