Administration of intravenous iron through a home-based infusion strategy is safe and has high patient acceptance.

BACKGROUND AND AIMS: To evaluate the safety and patient experience of a hospital-initiated home-based iron infusion service in patients with iron deficiency with or without anaemia. METHODS: Retrospective cohort study, including adult patients who received intravenous iron through a Hospital in The Home service in a single tertiary centre between August 2020 and 2021. A chart review was conducted for documented adverse events (AEs). A telephone survey assessed patient acceptance with three questions on a 5-point Likert scale: (i) How do you perceive the experience of having your infusion given in the home? (ii) Would you like to have the infusion in the same location if you require one in the future? and (iii) Do you feel safe having your infusion at home? OUTCOME MEASURES: Percentage of patients experiencing AEs and patient acceptance of a home-based iron infusion strategy. RESULTS: One hundred ninety-seven patients were included (181 ferric carboxymaltose and 16 ferric derisomaltose). Six (3%) patients (2 of 181 patients who received ferric carboxymaltose compared with 4 of 16 patients who received ferric derisomaltose, P < 0.001, Fisher's exact) experienced AEs, mostly headache and pruritus. Most patients who participated in the telephone survey had a positive experience (57/58 (98%)), felt safe (57/58 (98%)) and preferred future infusions to occur at home (52/58 (90%)). CONCLUSION: A home-based iron infusion strategy was safe and well accepted by patients. Larger studies evaluating the safety profile of different iron formulations in the home setting are required.

Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes.

BACKGROUND/AIMS: Low serum testosterone is common in cirrhotic men, but the impact of disease aetiology remains uncertain. This study compares serum total testosterone (TT) levels by disease aetiology and assesses its prognostic value. METHODS: Single-centre retrospective study of cirrhotic men who had TT levels measured between 2002 and 2020. A cut-off of 12 nmol/L was used to define low TT and 230 pmol/L for calculated free testosterone (cFT). Linear and logistic regression used to adjust for variables known to affect testosterone levels and assess for an association between levels and outcomes. RESULTS: Of 766 cirrhotic men, 33.3% had alcohol-related liver disease (ALD) and 11.9% had non-alcoholic fatty liver disease (NAFLD). The median age was 56 years (interquartile range (IQR) 50-61), and the model for end-stage liver disease (MELD) score 14 (IQR 9-20). TT levels were low in 53.3% of patients, (median 11.0 nmol/L; IQR 3.7-19.8) and cFT low in 79.6% (median 122 pmol/L; IQR 48.6-212). Median TT was lower in men with ALD (7.6 nmol/L; IQR 2.1-16.2) and NAFLD (9.8 nmol/L; IQR 2.75-15.6) compared to other aetiologies (11.0 nmol/L; IQR 3.73-19.8) (p < 0.001 for all), which remained true after adjustment for age and MELD score. TT was inversely associated with 12-month mortality or transplant (381 events, p = 0.02) and liver decompensation (345 events, p = 0.004). CONCLUSIONS: Low serum testosterone is common in cirrhotic men and is associated with adverse clinical outcomes. TT levels are significantly lower in ALD and NAFLD compared to other disease aetiologies. Further large-scale studies are required to assess the potential benefits of testosterone therapy.

Cardiac Risk Stratification in Liver Transplantation: Results of a Tiered Assessment Protocol Based on Traditional Cardiovascular Risk Factors.

Coronary artery disease (CAD) confers increased perioperative risk in patients undergoing liver transplantation (LT). Although routine screening for CAD is recommended, there are limited data on the effectiveness of screening strategies. We evaluated the safety and efficacy of a 3-tiered cardiac risk-assessment protocol that stratifies patients based on age and traditional cardiac risk factors. We peformed a single-center, prospective, observational study of consecutive adult patients undergoing LT assessment (2010-2017). Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) cardiac groups and received standardized investigations with selective use of transthoracic echocardiography (TTE), dobutamine stress echocardiography (DSE), computed tomography coronary angiography (CTCA), and coronary angiography (CA). Primary outcomes were cardiac events (CEs) and cardiovascular death up to 30 days after LT. Overall, 569 patients were included, with 76 patients identified as LR, 256 as IR, and 237 as HR. Cardiac risk factors included diabetes mellitus (26.0%), smoking history (47.3%), hypertension (17.8%), hypercholesterolemia (7.2%), family (17.0%) or prior history of heart disease (6.0%), and obesity (27.6%). Of the patients, 42.0% had ≥2 risk factors. Overall compliance with the protocol was 90.3%. Abnormal findings on TTE, DSE, and CTCA were documented in 3, 23, and 44 patients, respectively, and 12 patients were not listed for transplantation following cardiac assessment (1 LR, 2 IR, and 9 HR). Moderate or severe CAD was identified in 25.4% of HR patients on CTCA following a normal DSE. CEs were recorded in 7 patients (1.2%), with 2 cardiovascular deaths (0.4%). Cardiac risk stratification based on traditional cardiac risk factors with the selective use of DSE, CTCA, and CA is a safe and feasible approach that results in a low perioperative cardiac event rate.

The relationship between habitual dietary sodium intake and RAAS blockade on circulating microparticle levels in type two diabetes.

OBJECTIVE: Low sodium intake is paradoxically associated with adverse cardiovascular outcomes in individuals with type 2 diabetes mellitus (T2D), possibly from renin-angiotensin-aldosterone system (RAAS) activation, leading to endothelial dysfunction. In the present study, we investigated the associations between habitual sodium intake and RAAS blockade on endothelial function by measuring circulating microparticles (MPs) in individuals with T2D. METHODS: We conducted a prospective, cross-sectional study in 74 individuals with T2D. Habitual dietary sodium intake was estimated by using the mean of three corrected 24-h urine sodium excretion measurements (24hUNa). MP subtypes in platelet-free plasma were quantitated using flow cytometry. RESULTS: No associations between 24hUNa with levels of endothelial MPs were observed. Instead, a trend toward higher diabetes related CD36+/CD235a+ MP levels was associated with lower 24hUNa (rho = -0.23, P=0.05). When stratified according to tertiles of 24hUNa, platelet-derived CD42b+/CD41+ and CD42+/CD41+/Annexin V+ MPs were higher in the lowest tertile (24hUNa < 157 mmol/24 h) (P=0.02 respectively). Despite RAAS blockade being associated with lower levels of most MP subsets, it was not associated with lower MPs, in the setting of low sodium intake. CONCLUSION: Lower sodium intake is associated with higher circulating procoagulant MPs, but not with evidence of endothelial dysfunction in individuals with T2D.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care.

BACKGROUND: De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients. Cumulative immunosuppression has been shown to contribute to post-transplant malignancy (PTM) risk. There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs, independent of the net effect of immunosuppression. Calcineurin inhibitors such as tacrolimus may promote tumourigenesis, whereas mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, may limit tumour progression. Liver transplantation (LT) is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable, which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort. However, there is limited clinical data on this subject in both LT and other solid organ transplant recipients. AIM: To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation. METHODS: A literature search was conducted using MEDLINE and Embase databases using the key terms "solid organ transplantation", "tacrolimus", "mycophenolic acid", and "carcinogenicity", in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022. Related terms, synonyms and explosion of MeSH terms, Boolean operators and truncations were also utilised in the search. Reference lists of retrieved articles were also reviewed to identify any additional articles. Excluding duplicates, abstracts from 1230 records were screened by a single reviewer, whereby 31 records were reviewed in detail. Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria. RESULTS: A total of 6 studies were included in this review. All studies were large population registries or cohort studies, which varied in transplant era, type of organ transplanted and immunosuppression protocol used. Overall, there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation. Furthermore, no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients. CONCLUSION: The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies, and its application in solid organ transplantation, is yet to be confirmed in clinical studies. Thus, the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Non-Traumatic Hepatobiliary Emergencies.

Hepatobiliary emergencies typically present with a constellation of different symptoms including abdominal pain, fevers, nausea, vomiting, jaundice, coagulopathy, and in some instances, encephalopathy. The differential can be broad and may include infectious, inflammatory, and even iatrogenic etiologies. Workup with appropriate lab and imaging studies can help discern between different pathologies and thus guide their management. Interventions can range broadly from conservative management with medical therapy to endoscopic options or surgery. This article explores the diagnostic workup and evaluation as well as the current therapeutic interventions for a variety of these nontraumatic hepatobiliary emergencies based on the most current literature.

Introduction to Point-of-Care Ultrasonography.

Medical ultrasonography was first used as a diagnostic tool in 1942 by Theodore Karl Dussik to visualize brain structures. Use of ultrasonography broadened to the field of obstetrics in the 1950s and has since expanded to many other medical special-ties owing to ease of use, reproducibility, low cost, and lack of radiation. Advancements in ultrasonography technology have allowed clinicians to perform procedures with greater accuracy and to characterize tissue better than ever before. Piezoelectric crystals used to produce ultrasound waves have been replaced by silicon chips; artificial intelligence can be used to mitigate user variability; and more portable ultrasound probes are available for use with mobile devices. Ultrasonography requires training to be used appropriately, and patient and family education are crucial when performing an examination. Although some data are available regarding the amount of training needed for users to reach proficiency, this topic remains controversial and no standard currently exists.

Emergent laparoscopic surgical intervention for perforated hemorrhagic cholecystitis with hemodynamic instability.

Hemorrhagic cholecystitis is a rare diagnosis that closely mimics acute cholecystitis. Physical examination, laboratory studies and, in particular, computed tomography imaging allow for rapid diagnosis, stabilization and emergent surgical intervention. We describe our experience with three patients requiring emergent surgical intervention for hemorrhagic cholecystitis with unique clinical features including decreased platelet function due to liver cirrhosis, dual antiplatelet therapy and intraoperative finding of cholecystohepatic communication. Furthermore, we provide video recordings of two cases highlighting the severity of the disease. All presented patients were hemodynamically unstable and showed peritoneal signs on exam. Laboratory studies revealed moderate anemia and leukocytosis, while computed tomography suggested hemorrhage in the gallbladder. All patients required blood transfusions during their care and underwent laparoscopic cholecystectomy. Hemoperitoneum and gallbladder perforation were confirmed intraoperatively. Patients fully recovered without significant postoperative complications due to expedited operative management.

Post-training excitotoxic lesions of the dorsal hippocampus attenuate generalization in auditory delay fear conditioning.

An abundance of evidence indicates a role for the dorsal hippocampus (DH) in learning and memory. Pavlovian fear conditioning provides a useful model system in which to investigate DH function because conditioning to polymodal contextual cues, but generally not to discrete unimodal cues, depends upon the integrity of the DH. There is some suggestion that the hippocampus may be involved in generalization to discrete auditory stimuli following conditioning, but the available literature offers conflicting results regarding the nature of hippocampus involvement. The present experiments were designed to address a role for the DH in auditory generalization following delay fear conditioning. Rats were trained with two or 16 trials of delay fear conditioning and subsequently given a neurotoxic lesion of the DH or sham surgery. Upon recovery, they were tested for fear conditioned responding to the auditory stimulus they were trained with, as well as generalized responding to a novel auditory stimulus. Sham animals showed substantial generalization to the novel stimulus when trained with two or 16 trials. However, lesion animals showed much less generalization (better discriminative performance) to the novel stimulus following 16 conditioning trials while still showing substantial fear conditioned freezing to the trained stimulus. A second experiment showed that this effect was not the result of a non-associative response to the novel stimulus. We conclude that, with extended training, animals become capable of discriminating between trained and novel stimuli but another hippocampus-dependent process maintains generalized responding.

Sodium Intake, Circulating Microvesicles and Cardiovascular Outcomes in Type 2 Diabetes.

There is ongoing debate surrounding the complex relationship between dietary sodium intake and cardiovascular morbidity and mortality. The existing literature consists largely of observational studies that have demonstrated positive, negative, U-/J-shaped or unclear associations between sodium intake and cardiovascular outcomes. Our group and others have previously demonstrated an inverse relationship between dietary sodium intake and cardiovascular outcomes in people with type 2 diabetes. Increased activity of the renin-angiotensin-aldosterone system and sympathetic nervous system is postulated to contribute to these paradoxical findings through endothelial dysfunction, a precursor to the development of cardiovascular disease. Microvesicles are submicron (0.1 - 1.0µm) vesicles that form during cellular activation, injury or death with endothelial microvesicles being recognized markers of endothelial dysfunction. They are pathologically elevated in a variety of vascular-related conditions including type 2 diabetes. Lower habitual sodium intake in type 2 diabetes has been associated with higher pro-coagulant platelet microvesicles levels but not with endothelial microvesicles. Research utilizing endothelial microvesicles to evaluate the mechanistic relationship between dietary sodium intake and adverse cardiovascular outcomes in type 2 diabetes remains scarce.

Strategies for enumeration of circulating microvesicles on a conventional flow cytometer: Counting beads and scatter parameters.

Enumeration of circulating microvesicles (MVs) by conventional flow cytometry is accomplished by the addition of a known amount of counting beads and calculated from the formula: MV/µl = (MV count/bead count) × final bead concentration. We sought to optimize each variable in the equation by determining the best parameters for detecting 'MV count' and examining the effects of different bead preparations and concentrations on the final calculation. Three commercially available bead preparations (TruCount, Flow-Count and CountBright) were tested, and MV detection on a BD FACSCanto was optimized for gating by either forward scatter (FSC) or side scatter (SSC); the results were compared by calculating different subsets of MV on a series of 74 typical patient plasma samples. The relationship between the number of beads added to each test and the number of beads counted by flow cytometry remained linear over a wide range of bead concentrations (R2 ≥ 0.997). However, TruCount beads produced the most consistent (concentration variation = 3.8%) calculated numbers of plasma CD41+/Annexin V+ MV, which were significantly higher from that calculated using either Flow-Count or CountBright (p < 0.001). The FACSCanto was able to resolve 0.5 µm beads by FSC and 0.16 µm beads by SSC, but there were significantly more background events using SSC compared with FSC (3113 vs. 470; p = 0.008). In general, sample analysis by SSC resulted in significantly higher numbers of MV (p < 0.0001) but was well correlated with enumeration by FSC for all MV subtypes (ρ = 0.62-0.89, p < 0.0001). We conclude that all counting beads provided linear results at concentrations ranging from 6 beads/µl to 100 beads/µl, but TruCount was the most consistent. Using SSC to gate MV events produced high background which negatively affected counting bead enumeration and overall MV calculations. Strategies to reduce SSC background should be employed in order to reliably use this technique.

Pulmonary Hypertension in a Patient with Hereditary Hemorrhagic Telangiectasia.

t Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu Disease, is an autosomal dominant genetic disorder that is characterized by the abnormal development of blood vessels. While the pathophysiology underlying the development of pulmonary hypertension (PH) in patients with HHT is not fully understood, it is believed to occur by one of two mechanisms: increases in pulmonary vascular resistance or cardiac output. In the following report, we describe an interesting case of a 26-year-old woman with HHT whose right heart catheterization initially demonstrated PH with elements of both pre- and post-capillary PH. Once the pre-capillary PH component was treated, however, an underlying high-normal cardiac-output state was unmasked. [Full article available at http://rimed.org/rimedicaljournal-2017-08.asp].

Medical students help bridge the gap in sexual health education among middle school youth.

BACKGROUND: School-based programs are important in addressing risky teenage sexual behavior. We implemented a sex education program using trained medical student volunteers. METHODS: Medical students (n=30) implemented a seven-session curriculum, designed by medical students and faculty, to 7th and 8th grade students (n=310) at a local school. Middle school students completed pre- and post-assessments. Teachers and medical students completed questionnaires relating their perceptions of students' attitudes and understanding of sexual health. RESULTS: Students completing the curriculum scored 5% higher on post- versus pre-assessment (84% vs 78.7%, p<0.001). Statistically significant gains were noted in knowledge of reproductive system anatomy, community resources, and sexual decision making. Sixty percent of middle school teachers compared to only 16.7% of medical student volunteers reported discomfort teaching sexual health. DISCUSSION: Sexual education delivered by trained medical student volunteers may improve middle schoolers' understanding of sexual health. [Full article available at http://rimed.org/rimedicaljournal-2017-01.asp].

Influence of Medical Student Debt on the Decision to Pursue Careers in Primary Care.

PURPOSE: To determine if medical student debt has an effect on medical student specialty choice. METHODS: A cross-sectional survey was distributed to students at 12 medical schools across the United States to assess the effect of debt on specialty choice. RESULTS: In total, 415 students responded to the survey; 98 medical students reported that they were pursuing a primary care residency (PCR) and 250 reported that they were pursing a non-primary care residency (NPCR). There was no significant difference in average student loan debt anticipated by medical students pursing PCR and NPCR ($142,217 vs $150,784; P>0.46). Medical students pursuing a PCR reported lower estimated salaries on average than medical students pursuing NPCR ($137,711 vs $241,804; p<0.01). Of the surveyed students, 62% of students who are pursuing PCR and 77% of the students who are pursuing a NPCR would not have pursued medicine as a career if residents were responsible for paying tuition. CONCLUSION: This study revealed no significant difference between the student debt of medical students pursuing PCR compared to those who are pursuing a NPCR. However, a large majority of medical students would not pursue a career in medicine if faced with the responsibility of paying tuition for residency. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login].

Bowel perforation complicating an ACTH-secreting phaeochromocytoma.

ACTH-secreting phaeochromocytoma (ASP) is a rare cause of ACTH-dependent Cushing's syndrome (CS). We report the case of a 63-year-old female presenting with CS secondary to an ASP complicated by bowel perforation. This case report highlights ASP as an uncommon but important cause of ectopic ACTH secretion (EAS). There have been 29 cases of ASP, all of which were unilateral and benign, but associated with significant complications. Patients presenting with ASP have the potential for cure with unilateral adrenalectomy. Given this promising prognosis if recognised, ASP should be considered in the diagnostic workup of ACTH-dependent CS. As this case demonstrates, gastrointestinal complications can arise from severe hypercortisolaemia associated with CS. Early medical and surgical intervention is imperative as mortality approaches 50% once bowel perforation occurs. LEARNING POINTS: Consider phaeochromocytoma in the diagnostic workup of ACTH-dependent CS; screen with plasma metanephrines or urinary catecholamines.Serial screening may be required if ACTH-secreting phaeochromocytoma is suspected, as absolute levels can be misleading.Early catecholamine receptor blockade and adrenal synthesis blockade may avoid the need for rescue bilateral adrenalectomy in ACTH-secreting phaeochromocytoma.Consider early medical or surgical management when gastrointestinal features are present in patients with CS, as bowel perforation due to severe hypercortisolaemia can occur and is associated with significant mortality.