Defining the landscape of patient harm after osteopathic manipulative treatment: synthesis of an adverse event model.

BACKGROUND: In the United States, osteopathic manipulative treatment (OMT), is a popular complementary physical health approach for the treatment of neuromusculoskeletal disorders. However, post-OMT adverse events (AEs) are poorly defined in terms of frequency, severity, and temporal evolution. To date, no benchmark for patient safety exists. To improve understanding in this field, we set out to model the landscape of patient harm after OMT. METHODS: We conducted a comprehensive search of all available primary clinical research studies reporting on the occurrence of post-OMT AEs in nonpregnant, adult outpatients treated by an osteopathic physician in the United States. The methodology of eligible studies was then reviewed to select those containing the minimum required dataset to model the post-OMT AEs. The minimum required dataset consisted of four model parameters: 'post-OMT interval', 'OMT encounters with post-OMT interval assessment', 'AEs preceded by an OMT encounter', and 'AE severity.' We used the dataset extracted from selected studies to calculate a patient safety benchmark defined as the incidence rate of AEs per 100 post-OMT interval-days. RESULTS: From 212 manuscripts that we identified, 118 primary clinical research studies were assessed for eligibility. A total of 23 studies met inclusion criteria for methodological review, of which 13 studies passed and were selected for modeling. Mild AEs were the most frequent, accounting for n = 161/165 (98%) of total AEs observed in the literature. The cumulative incidence of mild AEs was also significantly greater (P = 0.01) than both moderate and severe grades. The benchmark incidence rate was 1.0 AEs per 100 post-OMT interval-days. CONCLUSIONS: The majority of post-OMT AEs observed in the primary clinical literature were of mild severity. Modeling of the combined dataset on post-OMT AEs allowed for the derivation of a patient safety benchmark that, to date, has not been established in the field of osteopathic manipulative medicine. Additional research is needed to improve model resolution during the post-OMT period. This work conceptualized a model for identifying and grading post-OMT AEs, which should facilitate future comparisons between institutions in order to continually improve patient safety standards in the field of osteopathic manipulative medicine.

Oxidative Stress Occurs Prior to Amyloid Aß Plaque Formation and Tau Phosphorylation in Alzheimer's Disease: Role of Glutathione and Metal Ions.

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder that affects millions of people worldwide. Although the pathogenesis remains obscure, there are two dominant causal hypotheses. Since last three decades, amyloid beta (Aß) deposition was the most prominent hypothesis, and the other is the tau hyperphosphorylation hypothesis. The confirmed diagnostic criterion for AD is the presence of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau and the deposition of toxic oligomeric Aß in the autopsied brain. Consistent with these hypotheses, oxidative stress (OS) is garnering major attention in AD research. OS results from an imbalance of pro-oxidants and antioxidants. There is a considerable debate in the scientific community on which process occurs first, OS or plaque deposition/tau hyperphosphorylation. Based on recent scientific observations of various laboratories including ours along with critical analysis of those information, we believe that OS is the early event that leads to oligomeric Aß deposition as well as dimerization of tau protein and its subsequent hyperphosphorylation. This OS hypothesis immediately suggests the consideration of novel therapeutic approaches to include antioxidants involving glutathione enrichment in the brain by supplementation with or without an iron chelator.

A highly discriminatory RNA strand-specific assay to facilitate analysis of the role of cis-acting elements in foot-and-mouth disease virus replication.

Foot-and-mouth-disease virus (FMDV), the aetiological agent responsible for foot-and-mouth disease (FMD), is a member of the genus Aphthovirus within the family Picornavirus. In common with all picornaviruses, replication of the single-stranded positive-sense RNA genome involves synthesis of a negative-sense complementary strand that serves as a template for the synthesis of multiple positive-sense progeny strands. We have previously employed FMDV replicons to examine viral RNA and protein elements essential to replication, but the factors affecting differential strand production remain unknown. Replicon-based systems require transfection of high levels of RNA, which can overload sensitive techniques such as quantitative PCR, preventing discrimination of specific strands. Here, we describe a method in which replicating RNA is labelled in vivo with 5-ethynyl uridine. The modified base is then linked to a biotin tag using click chemistry, facilitating purification of newly synthesised viral genomes or anti-genomes from input RNA. This selected RNA can then be amplified by strand-specific quantitative PCR, thus enabling investigation of the consequences of defined mutations on the relative synthesis of negative-sense intermediate and positive-strand progeny RNAs. We apply this new approach to investigate the consequence of mutation of viral cis-acting replication elements and provide direct evidence for their roles in negative-strand synthesis.

Acute beetroot juice reduces blood pressure in young Black and White males but not females.

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

A synaptic amplifier of hunger for regaining body weight in the hypothalamus.

Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight. Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear. Here, we probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons. We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.

Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

A Proprietary Herbal Blend Containing Extracts of Punica granatum Fruit Rind and Theobroma cocoa Seeds Increases Serum Testosterone Level in Healthy Young Males: A Randomized, Double-Blind Placebo-Controlled Study.

LN18178 is a proprietary herbal blend containing extracts of Punica granatum fruit rind and Theobroma cocoa seeds. The objective of the present study was to evaluate the effect of LN18178 on serum testosterone levels in healthy young adults in a randomized, double-blind, placebo-controlled study. One hundred and twenty male volunteers (age 21-35 years) were randomized into three groups. Each group (n = 40) received a daily dose of either placebo or 200 or 400 mg LN18178 for fifty-six days. An increase in serum testosterone (free and total) was the primary efficacy measure of the study. The secondary measures included dihydrotestosterone (DHT), cortisol, Luteinizing hormone (LH), 17ß-Estradiol (E2), hand grip strength, and the mid-upper arm circumferences (MUAC). The vital signs and clinical chemistry parameters in blood and urine were performed to determine product safety. Post-intervention, both doses of LN18178 significantly increased free testosterone (p < 0.0001 vs. baseline; p = 0.0268 and p < 0.0001, respectively vs. placebo). The high dose group showed significant increases in total testosterone (p < 0.0001 vs. baseline; p = 0.0184 vs. placebo) and luteinizing hormone (p < 0.0007 vs. baseline; p = 0.0470 vs. placebo). The changes in other hormones were not significant. At post-trial, the LN18178-400 group showed significant improvements in the hand grip strength and mid-upper arm circumference. The hemato-biochemical parameters, urinalysis, and vital signs of the participants were within the normal range. Together, these observations suggest that LN18178 is a safe and tolerable herbal blend; it increases testosterone level and increases muscle strength and MUAC in young, healthy males.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2035037 .

Ethnic differences in parental experiences during the first six months after PICU discharge in Singapore: a qualitative study.

Introduction: Literature on parental experiences after childhood critical illness has limited representation from diverse ethnic backgrounds. Parents from global ethnic majority groups have reported worst psychological outcomes and required more social support after childhood critical illness. Aim: To explore the experiences of Chinese, Malay, and Indian parents in the first six months after Pediatric Intensive Care Unit (PICU) discharge of their child in Singapore. Methods: Sequential semi-structured qualitative interviews were conducted to collect data from a convenience sample of 28 parents at one month (n = 28) and at six months (n = 22) after their child's discharge from a multidisciplinary PICU. Framework Analysis was adopted as the qualitative analysis strategy. The PICS-p framework was applied a priori in the Framework Analysis. Findings: Three interdependent domains and seven themes framed the 28 accounts in which ethnically diverse parents reported psychological stressors (PICS-p: emotional health), support received (PICS-p: social health) and practical challenges (transitional health) in the first six months after childhood critical illness. In the emotional health domain, parents were affected by different stressors and had different priorities over their child's survivorship. Only Indian parents reported experiences of stress symptoms, at six months post discharge. Malay parents sought solace from their religion more than Chinese and Indian parents. In the social health domain, parents reported various sources and degree of support received. Familial supports were strong across all groups, while community support was more prominent in Malay as compared to Chinese and Indian parents. A third domain, transitional health, was introduced to capture the difficulties parents faced during the transition from PICU survival to home. Parents from non-Chinese families were more likely to report financial challenges and more involvement of spouses after discharge. Complementary medicine or commercial health products were utilized by Chinese and Malay families. Conclusion: These findings reveal preferred strategies that parents from a global ethnic employ to address the emotional, social and transitional health impacts of their child's critical illness. Future care delivery may consider tailored care plans, communication strategies, and emotional support in PICUs that address the unique ethnic needs of parents during the critical six-months post their child's illness.

eHealth or e-Chaos: The use of Digital Health Interventions for Health Systems Strengthening in sub-Saharan Africa over the last 10 years: A scoping review.

Background: Digital health solutions are a potent and complementary intervention in health system strengthening to accelerate universal access to health services. Implementing scalable, sustainable, and integrated digital solutions in a coordinated manner is necessary to experience the benefits of digital interventions in health systems. We sought to establish the breadth and scope of available digital health interventions (DHIs) and their functions in sub-Saharan Africa. Methods: We conducted a scoping review according to the Joanne Briggs Institute's reviewers manual and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) checklist and explanation. We retrieved data from the WHO Digital Health Atlas (DHA), the WHO e-Health country profiles report of 2015, and electronic databases. The protocol has been deposited in an open-source platform - the Open Science Framework at https://osf.io/5kzq7. Results: The researchers retrieved 983 digital tools used to strengthen health systems in sub-Saharan Africa over the past 10 years. We included 738 DHIs in the analysis while 245 were excluded for not meeting the inclusion criteria. We observed a disproportionate distribution of DHIs towards service delivery (81.7%, n = 603), health care providers (91.8%, n = 678), and access and use of information (84.1%, n = 621). Fifty-three percent (53.4%, n = 394) of the solutions are established and 47.5% (n = 582) were aligned to 20% (n = 5) of the system categories. Conclusions: Sub-Saharan Africa is endowed with digital health solutions in both numbers and distinct functions. It is lacking in coordination, integration, scalability, sustainability, and equitable distribution of investments in digital health. Digital health policymakers in sub-Saharan Africa need to urgently institute coordination mechanisms to terminate unending duplication and disjointed vertical implementations and manage solutions for scale. Central to this would be to build digital health leadership in countries within SSA, adopt standards and interoperability frameworks; advocate for more investments into lagging components, and promote multi-purpose solutions to halt the seeming "e-chaos" and progress to sustainable e-health solutions.

Anionic polymers amplify electrokinetic perfusion through extracellular matrices.

Electrical stimulation (ES) promotes healing of chronic epidermal wounds and delays degeneration of articular cartilage. Despite electrotherapeutic treatment of these non-excitable tissues, the mechanisms by which ES promotes repair are unknown. We hypothesize that a beneficial role of ES is dependent on electrokinetic perfusion in the extracellular space and that it mimics the effects of interstitial flow. In vivo, the extracellular space contains mixtures of extracellular proteins and negatively charged glycosaminoglycans and proteoglycans surrounding cells. While these anionic macromolecules promote water retention and increase mechanical support under compression, in the presence of ES they should also enhance electro-osmotic flow (EOF) to a greater extent than proteins alone. To test this hypothesis, we compare EOF rates between artificial matrices of gelatin (denatured collagen) with matrices of gelatin mixed with anionic polymers to mimic endogenous charged macromolecules. We report that addition of anionic polymers amplifies EOF and that a matrix comprised of 0.5% polyacrylate and 1.5% gelatin generates EOF with similar rates to those reported in cartilage. The enhanced EOF reduces mortality of cells at lower applied voltage compared to gelatin matrices alone. We also use modeling to describe the range of thermal changes that occur during these electrokinetic experiments and during electrokinetic perfusion of soft tissues. We conclude that the negative charge density of native extracellular matrices promotes electrokinetic perfusion during electrical therapies in soft tissues and may promote survival of artificial tissues and organs prior to vascularization and during transplantation.

The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length-The difference between zero and one: A case report.

Introduction: Hyperbaric oxygen (HBO2) therapy has recently been suggested for the treatment of different brain injuries as well as for physical and cognitive enhancement. The author recently carried out a self-experiment to obtain objective information on the effects of HBO2 therapy on neurocognition, cardiopulmonary function, neuroimaging and its effect on novel biomarkers such as telomere length and proteomics. In the following case report, the author will present and discuss the results and the differences between zero and one. Methods: This is a personal case report on a single subject, myself, who underwent a protocol of 60 daily HBO2 therapy sessions within 3 months. Pre- and post-therapy objective evaluation measured included computerized cognitive assessment, brain imaging, cardiopulmonary exercise test, physical assessments and blood tests including telomere length and proteomics. Results: Neurocognitive results showed a 3.1-3.8% improvements in global cognitive function as well as all other cognitive function domains. In the perfusion MRI, there was a relative increase ranging from 43.3 to 52.3% in cerebral perfusion in various areas subserving memory, coordination, and visual motor cortex function. Similar improvements in cerebral perfusion were seen in the SPECT scans, which ranged from 8.79 to 16.12% increased perfusion in the temporal pole and entorhinal cortex subserving memory, as well as in the subcallosal area and lingual gyrus. MRI-DTI showed prominent increases in fractional anisotropy in several white matter areas including 9% in the body of the corpus callosum, 16.85% in for the fornix and 22.06% in the tapetum. In the physical domains, there were improvements in both anaerobic threshold, exercise endurance, muscle strength, gait speed and grip strength in the 7-15% range. The telomeres length was doubled and clusters of inflammatory proteins dropped around the 40th session and remained low at the 60th session. Conclusion: The difference between zero and one in this single case study of HBO2 therapy confirmed improvement in objective biomarkers which measured cognition, memory, brain processing speed, athletic performance and neuroimaging modalities measuring cerebral perfusion, blood flow and tractography. Additional studies with larger sample size and randomized clinical trials using similar biomarkers are needed to confirm the results and to delineate the longevity of these improvements.

Cardiotoxicity drug screening based on whole-panel intracellular recording.

Unintended binding of small-molecule drugs to ion channels affects electrophysiological properties of cardiomyocytes and potentially leads to arrhythmia and heart failure. The waveforms of intracellular action potentials reflect the coordinated activities of cardiac ion channels and serve as a reliable means for assessing drug toxicity, but the implementation is limited by the low throughput of patch clamp for intracellular recording measurements. In the last decade, several new technologies are being developed to address this challenge. We recently developed the nanocrown electrode array (NcEA) technology that allows robust, parallel, and long-duration recording of intracellular action potentials (iAPs). Here, we demonstrate that NcEAs allow comparison of iAP waveforms before and after drug treatment from the same cell. This self-referencing comparison not only shows distinct drug effects of sodium, potassium, and calcium blockers, but also reveals subtle differences among three subclasses of sodium channel blockers with sub-millisecond accuracy. Furthermore, self-referencing comparison unveils heterogeneous drug responses among different cells. In our study, whole-panel simultaneous intracellular recording can be reliably achieved with ∼94% success rate. The average duration of intracellular recording is ∼30 min and some last longer than 2 h. With its high reliability, long recording duration, and easy-to-use nature, NcEA would be useful for iAP-based preclinical drug screening.

Subcortical-cortical dynamical states of the human brain and their breakdown in stroke.

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.

Visual recognition of social signals by a tectothalamic neural circuit.

Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals1-5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms6-8. However, little is known about their perceptual mechanisms and executive neural circuits3. Here we trace the neuronal response to self-like biological motion9,10, a visual trigger for affiliation in developing zebrafish2,11. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function12-14. Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour.

Primary care physician referral practices regarding BRCA1/2 genetic counseling in a major health system.

PURPOSE: The United States Preventive Services Task Force recommends primary care physicians refer patients at high risk for BRCA1/2 mutations to genetic testing when appropriate. The objective of our study was to describe referrals for BRCA1/2 testing in a large integrated health system and to assess factors associated with referral. METHODS: This retrospective cohort study includes female patients between 18 and 50 years who had a primary care visit in the Cleveland Clinic Health System between 2010 and 2019. We used multivariable logistic regression to estimate differences in the odds of a woman being referred for BRCA1/2 testing by patient factors and referring physician specialty. We also assessed variation in referrals by physicians. RESULTS: Among 279,568 women, 5% were high risk. Of those, 22% were referred for testing. Black patients were significantly less likely to be referred than white patients (aOR 0.87; 95% CI 0.77, 0.98) and Jewish patients were more likely to be referred than non-Jewish patients (aOR 2.13; 95% CI 1.68, 2.70). Patients primarily managed by OB/GYN were significantly more likely to be referred than those cared for via Internal/Family Medicine (aOR 1.45; 95% CI 1.30, 1.61). Less than a quarter of primary care physicians ever referred a patient for testing. CONCLUSION: The majority of primary care patients at high risk for a BRCA1/2 mutation were not referred for testing, and over a decade, most physicians never referred a single patient. Internal/Family Medicine physicians, in particular, need support in identifying and referring women who could benefit from testing.

Acute paediatric inpatient care of children and young people admitted with self-harm or eating disorders: A single centre evaluation.

In the United Kingdom, the prevalence of children and young people (CYP) accessing acute paediatric inpatient care with mental health problems is increasing, with self-harm and eating disorders particularly prevalent. This study evaluated CYP experiences of being in receipt of acute paediatric inpatient care following either self-harm or crisis stemming from an eating disorder to inform domains for a person-centred outcome measure (PCOM). A series of stakeholder engagement events were conducted between April and July 2015 where creative approaches were used to explore stakeholder experiences of care and to identify outcome domains that were subsequently prioritised using a Nominal Group Technique. Data were analysed using inductive thematic approach, with significance scores calculated for domain statements. Ninety-six stakeholders (15 CYP, eight parents and carers, and 73 professionals) participated. Findings showed five priority PCOM domains: privacy and surveillance; holistic care; making choices, appropriate communication; working together to achieve care goals; and respect and empowerment. This single centre evaluation highlights the need for a PCOM to be developed for this patient group that comprehensively reflects stakeholders' expectations in order to inform improvements to quality of acute paediatric care.

Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association.

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases in an elderly population: outcomes from a single centre.

BACKGROUND: The prevalence of elderly patients with resectable colorectal peritoneal metastases (CRPM) is increasing. This study aimed to compare short and long-term outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPM in patients above and below 70 years of age. METHODS: This was a retrospective, 10-year analysis of 90-day major morbidity and mortality, and long-term survival. RESULTS: Thirty-two (21.3%) of 150 consecutive patients who underwent CRS and HIPEC during the study period were aged 70 and older. PCI (P = 0.04), perioperative chemotherapy use (P < 0.01) and organ resections (rectum P = 0.04, diaphragm P = 0.03) were less in the over 70 group. There was no significant differences in major morbidity (P = 0.19) and mortality (P = 0.32). There was also no difference in 5-year overall survival (OS) (≥70: 26% vs. <70: 39%; P = 0.68) and disease-free survival (DFS) (≥70: 25% vs. <70: 14%; P = 0.22). Age above 70 was not independently associated with worse OS (HR 1.55, P = 0.20) and DFS (HR 1.07, P = 0.81). CONCLUSION: The surgical management of CRPM appears safe and feasible in this elderly population. Appropriate selection of elderly patients for such radical intervention is reinforced by the comparable survival with those under 70.

The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis.

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial. METHODS: A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC. RESULTS: Twelve studies met the inclusion criteria (n = 2,463 patients). Ten were retrospective cohort, one was prospective cohort, and one was a prospective randomised by design. Patients who received NAC followed by CRS and HIPEC experienced no difference in major perioperative morbidity and mortality compared with patients who underwent surgery first (SF). There was no difference in overall survival at 3 years, but at 5 years NAC patients had superior survival (relative risk [RR] 1.31; 95% confidence interval [CI] 1.11-1.54, P < 0.001). There were no differences in 1- and 3-year, disease-free survival (DFS) between groups. Study heterogeneity was generally high across all outcome measures. CONCLUSIONS: Patients who received neoadjuvant chemotherapy did not experience any increase in perioperative morbidity or mortality. The potential improvement in 5-year overall survival in patients receiving NAC is based on limited confidence due to several limitations in the data, but not sufficiently enough to curtail its use. The practice of NAC in this setting will remain heterogeneous and guided by retrospective evidence until prospective, randomised data are reported.