Fatal hemolytic disease of the newborn due to anti-B Isohemagglutinin: An unfamiliar presentation of a familiar disease.

BACKGROUND: Hemolytic disease of the newborn (HDN) occurs in approximately 1 out of 3000 live births. Severe presentations are atypical but must be recognized and treated rapidly to avoid life-threatening organ dysfunction. CASE PRESENTATION: Here we report an unusual case of neonatal ABO HDN that illustrates the enormous inflammatory potential of maternal-fetal blood group mismatch. Following an uneventful delivery notable only for HDN caused by maternal anti-B IgG, our patient developed shock, DIC, and renal failure. Despite numerous interventions, she experienced a rapid clinical decline and died 10 days after birth. Treatment with whole blood exchange and a monoclonal antibody directed at complement component 5 (eculizumab) were attempted late in the disease course but were unsuccessful. Importantly, this patient had several known risk factors for severe ABO HDN, including the pentad of a group O mother with a group B neonate, high newborn red blood cell B antigen expression, presence maternal anti-B isohemagglutinin in high titer, presence of a maternal IgG anti-B isohemagglutinin, and African ancestry. CONCLUSION: Clinicians should be aware of the potential for severe ABO HDN and consider earlier diagnostic workup and more aggressive therapy in patients with high-risk features.

Validity of claims-based algorithms to identify neurodevelopmental disorders in children.

PURPOSE: To validate healthcare claim-based algorithms for neurodevelopmental disorders (NDD) in children using medical records as the reference. METHODS: Using a clinical data warehouse of patients receiving outpatient or inpatient care at two hospitals in Boston, we identified children (≤14 years between 2010 and 2014) with at least one of the following NDDs according to claims-based algorithms: autism spectrum disorder/pervasive developmental disorder (ASD), attention deficit disorder/other hyperkinetic syndromes of childhood (ADHD), learning disability, speech/language disorder, developmental coordination disorder (DCD), intellectual disability, and behavioral disorder. Fifty cases per outcome were randomly sampled and their medical records were independently reviewed by two physicians to adjudicate the outcome presence. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated. RESULTS: PPVs were 94% (95% CI, 83%-99%) for ASD, 88% (76%-95%) for ADHD, 98% (89%-100%) for learning disability, 98% (89%-100%) for speech/language disorder, 82% (69%-91%) for intellectual disability, and 92% (81%-98%) for behavioral disorder. A total of 19 of the 50 algorithm-based cases of DCD were confirmed as severe coordination disorders with functional impairment, with a PPV of 38% (25%-53%). Among the 31 false-positive cases of DCD were 7 children with coordination deficits that did not persist throughout childhood, 7 with visual-motor integration deficits, 12 with coordination issues due to an underlying medical condition and 5 with ADHD and at least one other severe NDD. CONCLUSIONS: PPVs were generally high (range: 82%-98%), suggesting that claims-based algorithms can be used to study NDDs. For DCD, additional criteria are needed to improve the classification of true cases.

The Use of Point-of-Care Ultrasound to Evaluate Pulsus Paradoxus in Children With Asthma.

Pulsus paradoxus (PP) is defined as a fall of systolic blood pressure of greater than 10 mm Hg during the inspiratory phase of respiration. Measurement of PP is recommended by national and international asthma guidelines as an objective measure of asthma severity but is rarely used in clinical practice. Cardiac point-of-care ultrasound with pulsed wave Doppler imaging measuring respiratory-phasic changes of mitral valve inflow velocities is well described in cardiac tamponade as "sonographic" PP. We present 10 cases of acute asthma presenting to an emergency department showing the finding of sonographic determined PP in the apical 4-chamber view of the heart on pulsed wave Doppler imaging.

Building a Bridge Between Pediatric Anesthesiologists and Pediatric Intensive Care.

Despite the aligned histories, development, and contemporary practices, today, pediatric anesthesiologists are largely absent from pediatric intensive care units. Contributing to this divide are deficits in exposure to pediatric intensive care at all levels of training in anesthesia and significant credentialing barriers. These observations have led us to consider, does the current structure of training lead to the ability to optimally innovate and collaborate in the delivery of pediatric critical care? We consider how redesigning the pediatric critical care training pathway available for pediatric anesthesiologists may improve care of children both in and out of the operating room by facilitating further sharing of skills, research, and clinical experience. To do so, we review the nuances of both training tracts and the potential benefits and challenges of facilitating greater integration of these aligned fields.

Integrating point-of-care ultrasound in the ED evaluation of patients presenting with chest pain and shortness of breath.

OBJECTIVE: The differential diagnoses of patients presenting with chest pain (CP) and shortness of breath (SOB) are broad and non-specific. We aimed to 1) determine how use of point-of-care ultrasound (POCUS) impacted emergency physicians' differential diagnosis, and 2) evaluate the accuracy of POCUS when compared to chest radiograph (CXR) and composite final diagnosis. METHODS: We conducted a prospective observational study in a convenience sample of patients presenting with CP and SOB to the Emergency Department (ED). Treating physicians selected possible diagnoses from a pre-indexed list of possible diagnoses of causes of CP and SOB. The final composite diagnosis from a chart review was determined as the reference standard for the diagnosis. The primary analysis involved calculations of sensitivity and specificity for POCUS identifiable diagnoses in detecting cause of CP and SOB. Additional comparative accuracy analysis with CXRs were conducted. RESULTS: 128 patients with a mean age of 64 ±â€¯17 years were included in the study. Using a reference standard of composite final diagnoses, POCUS had equal or higher specificity to CXR for all indications for which it was used, except for pneumonia. POCUS correctly identified all patients with pneumothorax, pleural effusion and pericardial effusion. In patients with a normal thoracic ultrasound, CXR never provided any actionable clinical information. Adding POCUS to the initial evaluation causes a significant narrowing of the differential diagnoses in which the median differential diagnosis from 5 (IQR 3-6) to 3 (IQR 2-4) p < 0.001. CONCLUSION: In evaluation of patients with CP and SOB, POCUS is a highly feasible diagnostic test which can assist in narrowing down the differential diagnoses. In patients with a normal thoracic ultrasound, the added value of a CXR may be minimal.

The Association Between Atherosclerosis and Low Back Pain: A Systematic Review.

OBJECTIVE: To assess the evidence of association between atherosclerosis and low back pain (LBP). TYPE: Focused systematic review. LITERATURE SURVEY: PubMed, Web of Science, CINAHL, and EMBASE were searched for original research articles, not limited by language, from January 1, 1990, to October 31, 2016. METHODOLOGY: Titles and then abstracts were identified using predefined search terms and excluded based on lack of relevancy. This was followed by full-text reviews. Two authors independently assessed methodological quality based on Cochrane Handbook for Systematic Reviews of Interventions. SYNTHESIS: A total of 26 studies met the inclusion criteria. The quality of the studies was low to moderate. There was significant heterogeneity across articles with respect to methodology. There was insufficient evidence to support an association between ischemia and low back pain. CONCLUSIONS: The cause of LBP remains poorly understood. Better insight into how intervertebral disk changes relate to LBP is needed to guide future research. High-quality prospective studies are needed to answer the question of whether atherosclerosis is a risk factor for LBP. LEVEL OF EVIDENCE: II.

A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis.

Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

Does Acupuncture Treatment Affect Utilization of Other Hospital Services at an Urban Safety-Net Hospital?

BACKGROUND: Little is known regarding the interaction between acupuncture and biomedical healthcare among vulnerable patient populations. In particular, the association between acupuncture and total cost of healthcare has not been characterized. METHODS: Total hospital system visits and associated charges were retrospectively reviewed among patients who received acupuncture at a large safety-net hospital system from 2007 to 2014. Inclusion criteria were Medicare or Medicaid insurance coverage, older than age 18 years, and one or more on-site acupuncture appointments. Patients were stratified into five groups based on the number of acupuncture visits: 1-3, 4-6, 7-9, 10-12, or 13-15 treatments. The total number of biomedical hospital visits and total associated charges were compared 6 months before and 6 months after initiation of acupuncture. RESULTS: A total of 329 patients met our inclusion criteria. Although not statistically significant, there appeared to be an association between acupuncture treatment and a decrease in total hospital charges. The group receiving 1-3 acupuncture treatments showed a per-patient average increase in total charges in the 6-month period after acupuncture ($1771.34; p = 0.38). The patients who received 7-9 treatments showed the largest average decrease in total charges ($8967.24; p = 0.17). CONCLUSION: This study shows a previously unreported aggregate relationship between number of treatments and total healthcare charges in a single urban safety-net hospital. Given the sample size available and the heterogeneity of the patient population, no statistically significant associations could be established between initiation of acupuncture treatment and charges. However, some suggestive patterns were observed. Further prospective studies with a matched-group control are warranted to further explore this relationship. Additional study across wider locations is warranted to best guide practitioners and hospitals in designing efficacious, high-value integrative medicine programs.

EMT and tumor metastasis.

EMT and MET comprise the processes by which cells transit between epithelial and mesenchymal states, and they play integral roles in both normal development and cancer metastasis. This article reviews these processes and the molecular pathways that contribute to them. First, we compare embryogenesis and development with cancer metastasis. We then discuss the signaling pathways and the differential expression and down-regulation of receptors in both tumor cells and stromal cells, which play a role in EMT and metastasis. We further delve into the clinical implications of EMT and MET in several types of tumors, and lastly, we discuss the role of epigenetic events that regulate EMT/MET processes. We hypothesize that reversible epigenetic events regulate both EMT and MET, and thus, also regulate the development of different types of metastatic cancers.

Public health in the Vilna Ghetto as a form of Jewish resistance.

We describe the system of public health that evolved in the Vilna Ghetto as an illustrative example of Jewish innovation and achievement during the Holocaust. Furthermore, we argue that by cultivating a sophisticated system of public health, the ghetto inmates enacted a powerful form of Jewish resistance, directly thwarting the intention of the Nazis to eliminate the inhabitants by starvation, epidemic, and exposure. In doing so, we aim to highlight applicable lessons for the broader public health literature. We hope that this unique story may gain its rightful place in the history of public health as an insightful case study of creative and progressive solutions to universal health problems in one of the most challenging environments imaginable.

A preliminary comparison of primary care use by refugees before and after acupuncture.

BACKGROUND: Limited research exits on utilization and cost-effectiveness of acupuncture among underserved communities, and virtually no evidence has been published with respect to refugee populations. In this study, we examined the relationship between acupuncture and the total utilization of primary care services in a cohort of refugee patients with chronic pain. METHODS: We retrospectively reviewed the medical records of 16 refugee patients with chronic pain at Boston Medical Center (BMC). The research was IRB-approved. Demographics and total charges associated with primary care over 18 months were collected. RESULTS: Total charges associated with primary care services decreased by 50.2% in our refugee cohort in the 12 months following acupuncture treatment, equivalent to a savings of $691 per patient per month. CONCLUSIONS: This preliminary review demonstrated a statistically significant decrease in total charges associated with primary care following acupuncture treatment (p=0.0308). This study suggests the need for further investigation of the relation between acupuncture and refugees with chronic pain, as well as the financial implications of this relationship. It is unclear why refugees may seek fewer primary care services after acupuncture treatment. Additional study is needed to further explore whether this relationship is generalizable to other hospital services and to other patient populations.

Drug resistance in cancer: an overview.

Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study.

Cancer development, progression, and therapy: an epigenetic overview.

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell-cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

Complementary and alternative medicine in the treatment of refugees and survivors of torture: a review and proposal for action.

Survivors of torture and refugee trauma often have increased needs for mental and physical healthcare. This is due in part to the complex sequelae of trauma, including chronic pain, major depressive disorder, posttraumatic stress disorder (PTSD) and somatization. This article reviews the scientific medical literature for the efficacy and feasibility of some complementary and alternative medicine (CAM) modalities including meditation, Ayurveda, pranayama/yogic breathing, massage/body-work, dance/movement, spirituality, yoga, music, Traditional Chinese Medicine and acupuncture, qigong, t'ai chi, chiropractic, homeopathy, aromatherapy and Reiki specifically with respect to survivors of torture and refugee trauma. We report that preliminary research suggests that the certain CAM modalities may prove effective as part of an integrated treatment plan for survivors of torture and refugee trauma. Further research is warranted.

Anti-breast cancer effects of histone deacetylase inhibitors and calpain inhibitor.

Development of new breast cancer therapies is needed, particularly as cells become refractory or develop increased drug resistance. In an effort to develop such treatments, class I and II histone deacetylases (HDACs), alone and in combination with other cytotoxic agents, are currently in clinical trial. Herein, we discuss the effects of histone deacetylase inhibitors (HDACi) when used in combination with calpeptin, an inhibitor of the regulatory protease, calpain. We present results of study in two breast cancer cells lines with distinct characteristics: MDA-MB-231 and MCF-7. When used in combination with calpeptin, two chemically distinct HDACi significantly inhibited growth and increased cell death by inducing cell-cycle arrest and apoptosis. MCF-7 cells exhibited a greater proportion of arrest at the G(1) phase, whereas triple-negative MDA-MB-231 cells exhibited increased cell cycle arrest at the S phase. Methylation of the imprinted and silenced proapoptoic tumor suppressor gene aplasia Ras homolog member I (ARHI) was reduced in both cell lines after treatment with HDACi. However, it was only re-expressed on such treatment in MDA-MB-231 cells, suggesting that re-expression operates under differential mechanisms in these two cell lines. Collectively, these results showed that the combination of HDACi and calpeptin inhibited the growth of two distinctly different types of breast cancer cells and could have wide clinical applications, though the mechanisms of inhibition are possibly different.