Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Bloodstream infections in prolonged use of axillary-placed, intra-aortic balloon-pump support: A single-center study.

Infections from prolonged use of axillary intra-aortic balloon pumps (IABPs) have not been well studied. Bloodstream infection (BSI) occurred in 13% of our patients; however, no difference in outcome was noted between those with BSI and those without. Further studies regarding protocol developments that minimize BSI risk are needed.

Outflow cannula alignment in continuous flow left ventricular devices is associated with stroke.

We sought to evaluate whether differences in left ventricular assist device (LVAD) canula alignment are associated with stroke. There is a paucity of clinical data on contribution of LVAD canulae alignment to strokes. We conducted a retrospective analysis of patients who underwent LVAD implantation at Houston Methodist hospital from 2011 to 2016 and included those who had undergone cardiac computed tomography (CT) with contrast. LVAD graft alignment using X-ray, echocardiography, and cardiac CT was evaluated. The primary outcome was stroke within 1 year of LVAD implantation. Of the 101 patients that underwent LVAD Implantation and cardiac CT scan during the study period, 78 met inclusion criteria. The primary outcome occurred in 12 (15.4%) patients with a median time to stroke of 77 days (interquartile range: 42-132 days). Of these, 10 patients had an ischemic and two had hemorrhagic strokes. The predominant device type was Heart Mate II (94.8%). Patients with LVAD outflow cannula to aortic angle lesser than 37.5° and those with outflow graft diameter of anastomosis less than 1.5 cm (assessed by cardiac CT) had significantly higher stroke risk (p < 0.001 and p = 0.01 respectively). In HMII patients, a lower LVAD speed at the time of CT scan was associated with stroke. Further studies are needed to identify optimal outflow graft configuration to mitigate stroke risk.

Remote versus early corticosteroid wean outcomes in heart transplant recipients in the contemporary era.

PURPOSE: The risks and benefits of remote corticosteroid weaning in heart transplant recipients more than 2 years post-transplant are unknown. We compared outcomes in patients undergoing early and remote steroid weaning after heart transplantation. METHODS: We performed a retrospective study (range 09, 1991-04, 2017). Primary outcomes included short-term and long-term mortality, allograft dysfunction, and burden of rejection. Secondary outcomes included impact on hemoglobin A1c, lipid panel, bone scan T-score, and body mass index. RESULTS: 63 patients underwent corticosteroid weaning between 2012 and 2017. Outcomes of patients weaned early (n = 34; median time from transplant = 1.1 years) were compared with those weaned late (n = 29; median time from transplant = 4.4 years). 52 (82.5%) patients were successfully weaned off corticosteroids. No statistically significant difference in outcomes was found between the early and late weaning groups (p = .20). There were no differences in allograft function (p-value = .16), incidence of rejection (p = .46), or mortality (p = .15). Improvement in metabolic profile was seen in both groups but was not statistically significant. CONCLUSIONS: In heart transplant recipients, remote vs early weaning of corticosteroids is not associated with significant differences in graft function or the incidence of rejection after 1-year follow-up. Moreover, there were no significant differences in survival up to 3 years between the two groups.

Management of Heart Failure, Durable Left Ventricular Assist Device, and Heart Transplant Patients in the COVID-19 Era.

Our world is facing recurrent waves of coronavirus disease 2019 (COVID-19) with the emergence of more infectious strains of the novel coronavirus, SARS-CoV-2. Multiple studies have established that heart failure (HF) patients are at high risk of severe disease and poor outcomes with COVID-19. Management of COVID-19 in patients with HF, heart transplant, and those supported with durable left ventricular assist devices present an arduous challenge due to underlying complex health conditions and overlap of symptoms. Based on available data, this review outlines the management of this vulnerable patient population who either present with COVID-19 with preexisting HF or with de novo HF from COVID-19.

Innovative Modeling Techniques and 3D Printing in Patients with Left Ventricular Assist Devices: A Bridge from Bench to Clinical Practice.

Left ventricular assist devices (LVAD) cause altered flow dynamics that may result in complications such as stroke, pump thrombosis, bleeding, or aortic regurgitation. Understanding altered flow dynamics is important in order to develop more efficient and durable pump configurations. In patients with LVAD, hemodynamic assessment is limited to imaging techniques such as echocardiography which precludes detailed assessment of fluid dynamics. In this review article, we present some innovative modeling techniques that are often used in device development or for research purposes, but have not been utilized clinically. Computational fluid dynamic (CFD) modeling is based on computer simulations and particle image velocimetry (PIV) employs ex vivo models that helps study fluid characteristics such as pressure, shear stress, and velocity. Both techniques may help elaborate our understanding of complications that occur with LVAD and could be potentially used in the future to troubleshoot LVAD-related alarms. These techniques coupled with 3D printing may also allow for patient-specific device implants, lowering the risk of complications increasing device durability.

Students' perception of portfolio as a learning tool at King Abdulaziz University Medical School.

BACKGROUND: Medical education has a longstanding tradition of using logbooks to record activities. The portfolio is an alternative tool to document competence and promote reflective practice. This study assessed the acceptance of portfolio use among Saudi undergraduate medical students. METHODS: Portfolios were introduced in the 2nd through 5th years at King Abdulaziz University over a two-year period (2013-2015). At the end of each academic year, students completed a mixed questionnaire that included a self-assessment of skills learned through the use of portfolio. RESULTS: The results showed a difference in focus between basic and clinical years: in basic years students' focus was on acquiring practical skills, but in clinical years they focused more on acquiring complex skills, including identifying and managing problems. The questionnaire responses nonetheless revealed a positive trend in acceptance (belief in the educational value) of portfolios among students and their mentors, across the years of the program. CONCLUSIONS: Using portfolios as a developmental learning and formative assessment tool in the early undergraduate years was found to contribute to students' ability to create their own clinical skills guidelines in later years, as well as to engage in and appreciate reflective learning.

Undergraduate medical students' perceptions of their learning experience in pediatric rotation at King Abdulaziz University Medical College in Jeddah, Saudi Arabia.

AIM: This study aimed to evaluate fifth-year medical students' perception of their learning experience during pediatric rotation at the medical college of King Abdulaziz University (KAU), Jeddah, Saudi Arabia. METHOD: This cross-sectional study was conducted by distributing a questionnaire to fifth-year students who attended the pediatric rotation at KAU, during 2013-2014. RESULTS: Three hundred fifty-six out of 360 students agreed to participate, representing a response rate of 99%. More than 90% were satisfied with the module, and 80% reported the usefulness of the orientation session. The mean scores for the usefulness of morning experience and afternoon activities were 7.20 ± 2.40 and 6.40 ± 2.70, respectively. A significant difference in the mean scores for supervision was observed between the clerkship sites (p = .0001), with the highest score for consultants' supervision (7.01 ± 2.90) and lowest for interns' supervision (4.81 ± 3.30). CONCLUSIONS: Overall, although the program was satisfactory to the majority of participants, areas of concern were identified. Students reported more effective learning and development of clinical skills , during the morning rounds, when supervised by consultants and senior specialists, and in activities that involved examining patients, presenting cases, and participating in discussions.

Portfolios in Saudi medical colleges. Why and how?

Over recent decades, the use of portfolios in medical education has evolved, and is being applied in undergraduate and postgraduate programs worldwide. Portfolios, as a learning process and method of documenting and assessing learning, is supported as a valuable tool by adult learning theories that stress the need for learners to be self-directed and to engage in experiential learning. Thoughtfully implemented, a portfolio provides learning experiences unequaled by any single learning tool. The credibility (validity) and dependability (reliability) of assessment through portfolios have been questioned owing to its subjective nature; however, methods to safeguard these features have been described in the literature. This paper discusses some of this literature, with particular attention to the role of portfolios in relation to self-reflective learning, provides an overview of current use of portfolios in undergraduate medical education in Saudi Arabia, and proposes research-based guidelines for its implementation and other similar contexts.

Frailty Assessment in Advanced Heart Failure.

BACKGROUND: Several studies have recently demonstrated the value of frailty assessment in a general heart failure (HF) population; however, it is unknown whether these findings are also applicable in advanced HF. We investigated the utility of frailty assessment and its prognostic value in elderly patients with advanced HF. METHODS: Forty consecutive elderly subjects aged ≥65 years, with left ventricular ejection fraction ≤35%, New York Heart Association class III or IV, and a 6-minute walk test <300 m were enrolled from the HF clinic at Montefiore Medical Center between October 2012 and July 2013. Subjects were assessed for frailty with the Fried Frailty Index, consisting of 5 components: hand grip strength, 15-foot walk time, weight loss, physical activity, and exhaustion. All subjects were prospectively followed for death or hospitalization. RESULTS: At baseline, the mean age of the cohort was 74.9 ± 6.5 years, 58% female, left ventricular ejection fraction 25.6 ± 6.4%, 6-minute walk test 195.8 ± 74.3 m and length of follow-up 454 ± 186 days. Thirty-five percent were prefrail and 65% were frail. Frailty status was associated with the combined primary endpoint of mortality and all-cause hospitalization (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.15-3.25, P = .013). On individual analysis, frailty was associated with all-cause hospitalizations (HR 1.92, 95% CI 1.12-3.27, P = .017) and non-HF hospitalizations (HR 3.31, 95% CI 1.14- 9.6, P = .028), but was not associated with HF hospitalizations alone (HR 1.31, 95% CI 0.68-2.49, P = .380). CONCLUSIONS: Frailty assessment in patients with advanced HF is feasible and provides prognostic value. These findings warrant validation in a larger cohort.

Predictors and management of right heart failure after left ventricular assist device implantation.

Newer generation continuous-flow left ventricular assist devices (LVADs) have overall improved outcomes with lower incidences of right ventricular failure (RVF) than their pulsatile predecessors, yet RVF still occurs in 9% to 40% of LVAD recipients. Post-implant, RVF is associated with poor outcomes, end-organ dysfunction, high mortality, and reduced survival to transplant. Therefore, preoperative risk stratification, appropriate patient selection, and optimal timing of implant are of paramount importance. In this article, we review the definition, incidence, pathophysiology, and current risk prediction models for RVF and touch on the contemporary management of RVF perioperatively and post-LVAD implant.

Trends in heart failure hospitalizations.

Heart failure (HF) requiring hospitalization can be defined as an admission to the hospital resulting in a calendar date change. According to the National Hospital Discharge Survey, the number of HF hospitalizations, either as a primary or secondary diagnosis, tripled between 1979 and 2004, and individuals over the age of 65 make 80 % of the prevalent cases of heart failure in the developed countries. HF is the most expensive Diagnosis Related Groups (DRG) diagnosis for hospitalizations in general, and the most frequent diagnosis for 30-day readmissions, incurring 15 billion in cost. To better understand and capture information, registries and trials have started to examine hospitalization rates and HF mortality, in addition to characterizing the hospitalized population. Registries exist worldwide. The role of emergency departments and HF clinics has become paramount in recognizing the preventable hospitalizations and 30-day readmissions, and cost containment.

Computed tomography and cardiac magnetic resonance imaging in pulmonary hypertension.

Recent advances in imaging technology have allowed for better temporal and spatial resolution in cardiovascular imaging. The idea of a "one-stop shop" for anatomical and functional cardiopulmonary and vascular assessment in patients with pulmonary hypertension is very appealing since diagnostic, prognostic, and therapeutic response can be measured. Modalities, such as computed tomography (CT) and cardiac magnetic resonance (CMR), are better suited to image the right heart and associated structures in multiple projections allowing for three-dimensional data sets and image reconstruction. This review will focus on the use of CT and CMR in the assessment of the right ventricle and pulmonary structures as they relate to pulmonary vascular disease.

Outcomes of Patients With Cocaine Induced Chest Pain in An Inner City Hospital.

BACKGROUND: Cocaine induced chest pain is a major reason for admission in Safety Net Hospitals in the United States. The majority of patients admitted undergo extensive work-up leading to enormous economic burden. We hypothesize that in individuals with low risk, cocaine does not further increase adverse cardiovascular outcomes. METHODS: We conducted a retrospective chart review of all patients admitted with chest pain to our hospital between 07/01/09 and 06/30/10. We excluded patients with modifiable risk factors for coronary artery disease (CAD). The study population was divided into cocaine and non-cocaine group based on urine drug screen. We analyzed data including demographic, laboratory, cardiac testing, detection of CAD, length of stay and mortality rates. RESULTS: A total of 426 individuals matched our inclusion and exclusion criteria and were considered to have no known modifiable cardiac risk factors; 54 in cocaine group and 372 in non-cocaine group. Based on physician discretion, 41(76%) in the cocaine group and 239(64%) in the non-cocaine group underwent various modalities of cardiac testing. Cardiac testing was positive in 6(2.5%) patients in non-cocaine group and none in the cocaine group (p=0.597). There was no significant difference between length of stay and in-hospital mortality between the two groups. CONCLUSIONS: In individuals at low risk for CAD, cocaine use resulted in higher rate of cardiac testing. However, there is no difference in prevalence of CAD and in-hospital mortality between the two groups. We conclude that cocaine does not increase adverse outcomes in patients with low risk for CAD.

Hemophagocytic Lymphohistiocytosis in Association With Clostridium difficile Infection and Cutaneous T-Cell Lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) or Macrophage Activation Syndrome (MAS) is a potentially life threatening disorder that presents with fever, suppressed blood cell counts, hepatosplenomegaly and multi-organ failure. HLH has been reported in association with genetic mutations, infections, autoimmune disorders, and various malignancies. However to the best of our knowledge, HLH in association with Clostridium difficile infection has never been reported. We present a case of HLH in a patient with Epstein-Barr virus (EBV) positive natural killer T (NKT) cell cutaneous lymphoma and active Clostridium difficile infection. A 35-year-old male with recently diagnosed EBV positive NKT cell lymphoma was admitted for Clostridium difficile associated diarrhea. During the course of hospitalization he gradually developed pancytopenia and multi-organ failure leading to death. Post-mortem examination confirmed the diagnosis of hemophagocytic lymphohistiocytosis.

States of serum leptin and insulin in children with epilepsy: risk predictors of weight gain.

BACKGROUND AND OBJECTIVES: Weight gain is an adverse metabolic effect in some children with epilepsy. The studies done to detect the effect of antiepileptic drugs and weight homeostatic hormones, insulin and leptin, were limited and controversial. MATERIALS AND METHODS: We evaluated the serum leptin and insulin as predictors of weight gain in children receiving long-term treatment with valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG). This study included 90 patients (treated: 70; untreated: 20). Serum lipid profile, insulin and leptin were measured. RESULTS: BMI, serum leptin and insulin were significantly elevated in VPA compared with controls, untreated patients and those treated with CBZ, LTG and combined therapy with LTG. Girls on VPA had higher BMI and leptin levels than boys. With VPA, serum insulin was correlated with BMI (r=0.625, p<0.01), leptin (r=0.823, p<0.001), treatment duration (r=0.775, p<0.01) and VPA dose (r=0.975, p<0.0001). Serum leptin was correlated with age (r=0.980, p<0.0001), BMI (r=0.704, p<0.01), serum insulin (r=0.823, p<0.001), LDL-c (r=0.630, p<0.01), HDL-c (r=-0.880, p<0.001), treatment duration (r=0.770, p<0.01) and VPA dose (r=0.970, p<0.001). BMI is correlated with serum insulin, leptin, LDL-c (r=0.835, p<0.001) and HDL-c (r=-0.955, p<0.0001). CONCLUSION: Hyperinsulinemia and hyperleptinemia are common with VPA and marked among epileptic children who gained weight suggesting states of insulin and leptin resistances. These alterations were not demonstrated with CBZ or LTG. The relationship between VPA, leptin and weight seems to be gender specific. Serum leptin may serve as a sensitive parameter for weight gain and reduction with intervention programs during follow-up of girls with epilepsy.

The need for national medical licensing examination in Saudi Arabia.

BACKGROUND: Medical education in Saudi Arabia is facing multiple challenges, including the rapid increase in the number of medical schools over a short period of time, the influx of foreign medical graduates to work in Saudi Arabia, the award of scholarships to hundreds of students to study medicine in various countries, and the absence of published national guidelines for minimal acceptable competencies of a medical graduate. DISCUSSION: We are arguing for the need for a Saudi national medical licensing examination that consists of two parts: Part I (Written) which tests the basic science and clinical knowledge and Part II (Objective Structured Clinical Examination) which tests the clinical skills and attitudes. We propose this examination to be mandated as a licensure requirement for practicing medicine in Saudi Arabia. CONCLUSION: The driving and hindering forces as well as the strengths and weaknesses of implementing the licensing examination are discussed in details in this debate.

Pattern of sepsis and meningitis in a University Hospital.

OBJECTIVE: To define the clinical and cerebrospinal fluid (CSF) criteria that establishes a diagnosis of sepsis and meningitis immediately on admission. METHODS: One thousand children, aged one day to 13 years, presenting with acute onset of vomiting, fever, convulsion, and diarrhea to the Pediatrics Department, King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia from January 1997 to December 2000 were evaluated. Cases were subjected to history, clinical examination, and lumbar puncture (LP). On admission, chemical, cytological, and bacteriological examinations of blood and CSF were carried out. Patients were divided into sepsis (n=94) and meningitis (n=26) groups. RESULTS: The most common age liable for LP was in the neonatal period (35.8%). Septic cases were more than meningitis (78.3% versus 21.7%). Neonates were the most commonly affected age in sepsis and meningitis; and the predominant symptom in all groups was vomiting. In meningitis, hemoglobin was less (p<0.05) while, blood white blood cell counts (WBCs) (p<0.05), blood neutrophils (p<0.05), CSF-chloride (p<0.000) and CSF-WBCs (p<0.001) were more than sepsis. In meningitis, a positive correlation was found between CSF-glucose with WBCs (r=0.52, p<0.05), neutrophils (r=0.49, p<0.05), and blood-glucose (r=0.56, p<0.01); and between CSF-WBCs and CSF-protein (r=0.55, p<0.01). In sepsis, a positive correlation was found between CSF-lymphocyte and CSF-red blood cell count (r=0.37, p<0.001). CONCLUSION: More septic cases were admitted to the Pediatric Department through Emergency than meningitis cases. The most common pediatric patients liable to LP were neonates, and the most common presenting symptom was vomiting. Children with vomiting and convulsion and no organism in CSF must be carefully examined, and urine and blood culture must be collected. These children must be closely observed in hospital and re-evaluated by a pediatrician.

A prospective study of congenital malformations among live born neonates at a University Hospital in Western Saudi Arabia.

OBJECTIVE: To estimate the incidence of major and minor congenital malformations among liveborn infants at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Estimation of risk factors were also evaluated. METHODS: Between March 2004 and May 2005, a total of 5356 babies born at King Abdulaziz University Hospital, were enrolled in this study for malformations. Details of cases were recorded after parents' interviews, clinical, radiological, and laboratory evaluations. RESULTS: One hundred and forty-seven (27.06/1000 livebirth) and 13 (2.39/1000 birth) stillbirth had congenital anomalies. In all livebirth, incidences of major anomalies were 93.9% and minor were 6.1%. Mothers of 95.9% with congenital malformation were healthy, 3.4% were diabetic and 0.7% had cardiac malfomation. In 38.8% of cases parents were consanguineous. Among the liveborn births, the most common system involved was cardiovascular (7.1/1000), followed by musculoskeletal/limb (4.1/1000), external genitalia (2.8/1000), urinary (2.6/1000), multiple chromosomal (2.2/1000), orofacial (1.9/1000), central nervous system (1.9/1000), skin (1.7/1000), multiple single gene (1.3/1000), multiple sequence (0.75/1000), eyes (0.56/1000), unclassified (0.19/1000), musculoskeletal/abdominal (0.19/1000), endocrine (0.19/1000). CONCLUSION: High incidence of major malformation in Jeddah. Importance of Genetic Counseling is revealed in our study since more than three quarters of mothers were under 36 years, and may well plan future pregnancies.

Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis.

OBJECTIVE: To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. METHODS: Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n = 28), meningitis (n = 7), and healthy controls (n = 16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n = 6), group 2 = clinical sepsis (n = 14), and group 3 = possible-infected (n = 8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer. RESULTS: In sepsis and meningitis patients, serum levels of CRP (p < 0.01, p < 0.05,) and IL-1alpha (p < 0.001, p < 0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p < 0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p < 0.05, p < 0.001, p < 0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). CONCLUSION: Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis.