Effect of the non-application of the motorcycle male passenger restriction policy on the risk of homicides in Cali, Colombia.

BACKGROUND: Restrictions of male passengers of motorcycles to prevent homicides is a long-standing policy in Cali, Colombia. For some periods of time, the policy was suspended and then put into action again. All these changes were never evaluated and there has been controversy due to the perception of citizens, specifically motorcycle users, that the law was properly implemented in some periods and poorly applied in others. Our aim was to examine the effect of the non-application of the motorcycle male passenger restriction policy on the risk of homicides in Cali, Colombia. METHODS: Ecologic study conducted using an interrupted time series analysis. The main outcome was the aggregated daily counts of homicides. Secondary outcomes were the aggregated daily counts of homicides using a motorcycle and using motorcycle and firearm. Incidence rate ratios (IRR) were obtained by comparing periods of policy implementation with periods of lack of implementation in autoregressive negative binomial regression models. RESULTS: There was an increased risk of homicides when the policy was not implemented (IRR=1.12; 1.05-1.19). There was no effect on the risk of homicides committed in motorcycles (IRR=0.98; 0.88-1.10) and when a motorcycle and firearm were used (IRR=0.99; 0.89-1.10). CONCLUSIONS: The lack of implementation of the ban of motorcycle male passengers was associated with an increased risk of homicides. Our findings support the importance of this policy to prevent homicides in Cali, Colombia. Future work should examine how this policy influences other policies related to prevent homicide and violent risk-related behaviour.

Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients.

BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.

Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.

Computational Fluid Dynamic Modeling of Urethral Strictures.

PURPOSE: Computational fluid dynamics have paradigm shifting potential in understanding the physiological flow of fluids in the human body. This translational branch of engineering has already made an important clinical impact on the study of cardiovascular disease. We evaluated the feasibility and applicability of computational fluid dynamics to model urine flow. MATERIALS AND METHODS: We prepared a computational fluid dynamics model using an idealized male genitourinary system. We created 16 hypothetical urethral stricture scenarios as a test bed. Standard parameters of urine such as pressure, temperature and viscosity were applied as well as typical assumptions germane to fluid dynamic modeling. We used ABAQUS/CAE 6.14 (Dassault Systèmes®) with a direct unsymmetrical solver with standard (FC3D8) 3D brick 8Node elements for model generation. RESULTS: The average flow rate in urethral stricture disease as measured by our model was 5.97 ml per second (IQR 2.2-10.9). The model predicted a flow rate of 2.88 ml per second for a single 5Fr stricture in the mid bulbar urethra when assuming all other variables constant. The model demonstrated that increasing stricture diameter and bladder pressure strongly impacted urine flow while stricture location and length, and the sequence of multiple strictures had a weaker impact. CONCLUSIONS: We successfully created a computational fluid dynamics model of an idealized male urethra with varied types of urethral strictures. The resultant flow rates were consistent with the literature. The accuracy of modeling increasing bladder pressure should be improved by future iterations. This technology has vast research and clinical potential.

The landscape of urological retractions: the prevalence of reported research misconduct.

OBJECTIVES: To evaluate the landscape of retractions of literature and to determine the prevalence of research misconduct in the field of urology. METHODS: Three databases (PUBMED, Embase, Retraction Watch) were queried for all retracted studies on urological topics in both urological and non-urological journals from April 1999 to March 2018. Two reviewers screened the records and determined the final list of articles to be included in the analysis. RESULTS: A total of 138 articles met the inclusion criteria. Over 80% of retractions occurred after 2009. Retractions originated from 76 different journals (13 urological journals) and 28 countries. The most common reasons for retraction were plagiarism (28%), fake peer review (20%), error (20%), and falsification of data (13%). Misconduct accounted for two-thirds of the retractions (n = 93). A large watermark, indicating retraction of the article, was present in 75% of the manuscripts. Articles were cited a total of 4454 times, 38% of citations happened after retraction. The majority of retracted articles related to urological oncology (70%). The highest number of retractions for an individual author was five. Rates of retraction among popular urological journals since 2010 have increased but remain a small proportion of all publications: BJUI, 0.189%; World Journal of Urology, 0.132%; European Urology, 0.058%; Urology, 0.047%; and Journal of Urology, 0.024%. CONCLUSION: Retractions of urological literature, similarly to retractions of other biomedical literature, have been rising over the last decade. The majority of these retractions stem from research misconduct. Despite retractions, flawed articles continued to be cited.

Perspectives From Authors and Editors in the Biomedical Disciplines on Predatory Journals: Survey Study.

BACKGROUND: Predatory journals fail to fulfill the tenets of biomedical publication: peer review, circulation, and access in perpetuity. Despite increasing attention in the lay and scientific press, no studies have directly assessed the perceptions of the authors or editors involved. OBJECTIVE: Our objective was to understand the motivation of authors in sending their work to potentially predatory journals. Moreover, we aimed to understand the perspective of journal editors at journals cited as potentially predatory. METHODS: Potential online predatory journals were randomly selected among 350 publishers and their 2204 biomedical journals. Author and editor email information was valid for 2227 total potential participants. A survey for authors and editors was created in an iterative fashion and distributed. Surveys assessed attitudes and knowledge about predatory publishing. Narrative comments were invited. RESULTS: A total of 249 complete survey responses were analyzed. A total of 40% of editors (17/43) surveyed were not aware that they were listed as an editor for the particular journal in question. A total of 21.8% of authors (45/206) confirmed a lack of peer review. Whereas 77% (33/43) of all surveyed editors were at least somewhat familiar with predatory journals, only 33.0% of authors (68/206) were somewhat familiar with them (P<.001). Only 26.2% of authors (54/206) were aware of Beall's list of predatory journals versus 49% (21/43) of editors (P<.001). A total of 30.1% of authors (62/206) believed their publication was published in a predatory journal. After defining predatory publishing, 87.9% of authors (181/206) surveyed would not publish in the same journal in the future. CONCLUSIONS: Authors publishing in suspected predatory journals are alarmingly uninformed in terms of predatory journal quality and practices. Editors' increased familiarity with predatory publishing did little to prevent their unwitting listing as editors. Some suspected predatory journals did provide services akin to open access publication. Education, research mentorship, and a realignment of research incentives may decrease the impact of predatory publishing.

Pharmacological Targeting of the ER-Resident Chaperones GRP94 or Cyclophilin B Induces Secretion of IL-22 Binding Protein Isoform-1 (IL-22BPi1).

Of the three interleukin-22 binding protein (IL-22BP) isoforms produced by the human IL22RA2 gene, IL-22BPi2 and IL-22BPi3 are capable of neutralizing IL-22. The longest isoform, IL-22BPi1, does not bind IL-22, is poorly secreted, and its retention within the endoplasmic reticulum (ER) is associated with induction of an unfolded protein response (UPR). Therapeutic modulation of IL-22BPi2 and IL-22BPi3 production may be beneficial in IL-22-dependent disorders. Recently, we identified the ER chaperones GRP94 and cyclophilin B in the interactomes of both IL-22BPi1 and IL-22BPi2. In this study, we investigated whether secretion of the IL-22BP isoforms could be modulated by pharmacological targeting of GRP94 and cyclophilin B, either by means of geldanamycin, that binds to the ADP/ATP pocket shared by HSP90 paralogs, or by cyclosporin A, which causes depletion of ER cyclophilin B levels through secretion. We found that geldanamycin and its analogs did not influence secretion of IL-22BPi2 or IL-22BPi3, but significantly enhanced intracellular and secreted levels of IL-22BPi1. The secreted protein was heterogeneously glycosylated, with both high-mannose and complex-type glycoforms present. In addition, cyclosporine A augmented the secretion of IL-22BPi1 and reduced that of IL-22BPi2 and IL-22BPi3. Our data indicate that the ATPase activity of GRP94 and cyclophilin B are instrumental in ER sequestration and degradation of IL-22BPi1, and that blocking these factors mobilizes IL-22BPi1 toward the secretory route.

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55.

An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, but the biological reasons underlying this association are unknown. We characterized the expression of ANKRD55 in human PBMCs and cell lines. Three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4(+) T cells but were virtually absent in CD8(+), CD14(+), CD19(+), and CD56(+) cells. Rs6859219 was significantly associated with ANKRD55 transcript levels in PBMCs and CD4(+) T cells and, thus, coincides with a cis-expression quantitative trait locus. The processed noncoding transcript 007 was the most highly expressed variant in CD4(+) T cells, followed by 001 and 005, respectively, but it was not detected in Jurkat, U937, and SH-SY5Y cell lines. Homozygotes for the risk allele produced more than four times more transcript copies than did those for the protective allele. ANKRD55 protein isoforms 005 and 001 were predominantly located in the nucleus of CD4(+) T cells and Jurkat and U937 cells. ANKRD55 was produced by primary cultures of murine hippocampal neurons and microglia, as well as by the murine microglial cell line BV2, and it was induced by inflammatory stimuli. ANKRD55 protein was increased in the murine mouse model of experimental autoimmune encephalomyelitis. Flow cytometric analysis of CNS-infiltrating mononuclear cells showed that CD4(+) T cells and monocytes expressed ANKRD55 in experimental autoimmune encephalomyelitis mice, with the higher fluorescence intensity found in CD4(+) cells. A low percentage of microglia also expressed ANKRD55. Together, these data support an important role for ANKRD55 in multiple sclerosis and neuroinflammation.

The relationship between frailty, incontinence severity, and treatment decisions for men with post-prostatectomy stress urinary incontinence: a mixed methods analysis.

Background: Frailty is common among urology patients in general as well as among men seeking evaluation for stress urinary incontinence (SUI), with 6.1% of men undergoing artificial urinary sphincter placement considered frail. It is unclear if and how patient views on frailty and incontinence severity impact decision-making with regards to SUI treatment. Methods: We undertook a mixed methods analysis to evaluate the intersection of frailty, incontinence severity, and treatment decision-making is presented. To do so, we utilized a previously published cohort of men undergoing evaluation for SUI at the University of California, San Francisco between 2015 and 2020, selecting those who had evaluation with timed up and go test (TUGT), objective measures of incontinence, and patient-reported outcome measures (PROMs). A subset of these participants had additionally undergone semi-structured interviews, and these interviews were re-examined to thematically code them with a focus on the impact of frailty and incontinence severity on SUI treatment decision-making. Results: Among the original cohort of 130 patients, 72 had an objective measure of frailty and were included in our analysis; 18 of these individuals had corresponding qualitative interviews. Common themes identified included (I) impact of incontinence severity on decision-making; (II) the interaction between frailty and incontinence; (III) the impact of comorbidity on treatment decision-making; and (IV) age as a construct of frailty and impact on surgical choice and/or recovery. Direct quotations regarding each theme provides insight into patients' views and drivers of SUI treatment decision-making. Conclusions: The impact of frailty on treatment decision-making for patients with SUI is complex. This mixed methods study highlights the variety of patient views on frailty with regards to surgical intervention for male SUI. Urologists should make a concerted effort to personalize patient counseling for SUI management and take time to understand each patient's perspective in order to individualize SUI treatment decision-making. More research is needed to help identify factors that influence decision-making for frail male patients with SUI.

Effect of the modified Glasgow Coma Scale score criteria for mild traumatic brain injury on mortality prediction: comparing classic and modified Glasgow Coma Scale score model scores of 13.

BACKGROUND: The Glasgow Coma Scale (GCS) classifies traumatic brain injuries (TBIs) as mild (14-15), moderate (9-13), or severe (3-8). The Advanced Trauma Life Support modified this classification so that a GCS score of 13 is categorized as mild TBI. We investigated the effect of this modification on mortality prediction, comparing patients with a GCS score of 13 classified as moderate TBI (classic model) to patients with GCS score of 13 classified as mild TBI (modified model). METHODS: We selected adult TBI patients from the Pennsylvania Outcome Study database. Logistic regressions adjusting for age, sex, cause, severity, trauma center level, comorbidities, and isolated TBI were performed. A second evaluation included the time trend of mortality. A third evaluation also included hypothermia, hypotension, mechanical ventilation, screening for drugs, and severity of TBI. Discrimination of the models was evaluated using the area under receiver operating characteristic curve (AUC). Calibration was evaluated using the Hosmer-Lemershow goodness of fit test. RESULTS: In the first evaluation, the AUCs were 0.922 (95% CI, 0.917-0.926) and 0.908 (95% CI, 0.903-0.912) for classic and modified models, respectively. Both models showed poor calibration (p < 0.001). In the third evaluation, the AUCs were 0.946 (95% CI, 0.943-0.949) and 0.938 (95% CI, 0.934-0.940) for the classic and modified models, respectively, with improvements in calibration (p = 0.30 and p = 0.02 for the classic and modified models, respectively). CONCLUSION: The lack of overlap between receiver operating characteristic curves of both models reveals a statistically significant difference in their ability to predict mortality. The classic model demonstrated better goodness of fit than the modified model. A GCS score of 13 classified as moderate TBI in a multivariate logistic regression model performed better than a GCS score of 13 classified as mild.

Structural and chemical heterogeneities of primary hyperoxaluria kidney stones from pediatric patients.

OBJECTIVE: Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the differences in structure and chemical composition between oxalate stones from patients from three groups: 1) pediatric patients that were genetically predisposed (primary hyperoxaluria) to form stones (PPH); 2) control pediatric patients that did not have such genetic predisposition (PN-PH); 3) adult patients that formed oxalate stones without the genetic predisposition (A-CaOx). A variety of instrumental analyses were conducted to identify physicochemical properties of stones characteristic of predisposed pediatric (PPH), pediatric hyperoxaluria (PN-PH), and adult (A-CaOx) patient populations. METHODS: Genetic variants of 16 stone-forming patients were determined using whole-exome gene sequencing. Components of stones from PPH (n = 6), PN-PH (n = 5), and A-CaOx (n = 5) groups were identified using Fourier transform infrared (FTIR) spectroscopy. Stone morphology and density were evaluated using high resolution X-ray computed tomography (micro-XCT). Stone microstructure and elemental composition were mapped with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively. RESULTS: Calcium oxalate bipyramidal crystals were found on stones from all groups. Stones from PPH patients with PH types I and II were composed of calcium oxalate monohydrate (COM) with relatively uniform mineral density (1224 ± 277 mg/cc) and distinct smooth surfaces. By contrast, micro-spherical calcium phosphate particles were found only on PN-PH stones, which also showed a broader range of mineral densities (1266 ± 342 mg/cc). Stones from the PN-PH group also contained phosphorus (P), which was absent in NP-PH stones. A-CaOx stones were of significantly lower mineral density (645 ± 237 mg/cc) than pediatric stones and were more heterogeneous in their elemental composition. CONCLUSION: Unique structural and compositional characteristics were identified in stones from pediatric patients with primary hyperoxaluria. These include the absence of phosphorus, a narrower mineral density distribution, and a uniform elemental composition compared to stones from pediatric patients without the genetic predisposition. Thus, characterization of stones at the macro- and micro-scales in combination with genetic testing of patients can provide insights and accurate diagnosis to develop a treatment plan for effective patient care.

Nedosiran Dramatically Reduces Serum Oxalate in Dialysis-Dependent Primary Hyperoxaluria 1: A Compassionate Use Case Report.

Primary hyperoxaluria 1 (PH1) is a devastating condition involving recurrent urolithiasis, early end-stage renal disease and multisystemic deposition of calcium oxalate crystals. Treatment options for PH1 are limited, inevitably requiring transplantation, usually combined kidney and liver transplant. Here we report successful compassionate use of Nedosiran, an RNA interference targeting lactate dehydrogenase, in an index patient. Monthly Nedosiran injections led to dramatically decreased plasma oxalate levels, decreased frequency of weekly hemodialysis sessions from 6 to 3, and deferral of combined kidney and liver transplant. Nedosiran represents a novel and impactful potential therapeutic for PH1 patients with end-stage renal disease.

Structure and elemental composition of Ceftriaxone induced pediatric nephrolithiasis.

Ceftriaxone is a widely used antibiotic because to its broad-spectrum gram-negative coverage, safety, and biological half life (5-9 h) permit dose once-daily administration. It is specifically used in pediatric patients in developing countries. Ceftriaxone forms insoluble sludge/stone when combined with calcium in the urinary system. In this study, Ceftriaxone induced sludge/stones from pediatric patients were collected to identify its microstructure and composition to gather insights into the mechanism of Ceftriaxone induced sludge/stone formation. The results illustrated that Ceftriaxone induced stones formed rapidly following antibiotic administration. Ceftriaxone calcium salt crystals could easily be broken with minimal intervention. However, Ceftriaxone combined with calcium phosphate formed an insoluble stone aggregate.

Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells.

Intronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4+ T lymphocytes of healthy controls. The biological function of ANKRD55, its role in the immune system, and cellular sources of expression other than lymphocytes remain uncharacterized. Here, we show that monocytes gain capacity to express ANKRD55 during differentiation in immature monocyte-derived dendritic cells (moDCs) in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). ANKRD55 expression levels are further enhanced by retinoic acid agonist AM580 but downregulated following maturation with interferon (IFN)-γ and lipopolysaccharide (LPS). ANKRD55 was detected in the nucleus of moDC in nuclear speckles. We also analyzed the adjacent IL6ST, IL31RA, and SLC38A9 genes. Of note, in healthy controls, MS risk SNP genotype influenced ANKRD55 and IL6ST expression in immature moDC in opposite directions to that in CD4+ T cells. This effect was stronger for a partially correlated SNP, rs13186299, that is located, similar to the main MS risk SNPs, in an ANKRD55 intron. Upon analysis in MS patients, the main GWAS MS risk SNP rs7731626 was associated with ANKRD55 expression levels in CD4+ T cells. MoDC-specific ANKRD55 and IL6ST mRNA levels showed significant differences according to the clinical form of the disease, but, in contrast to healthy controls, were not influenced by genotype. We also measured serum sgp130 levels, which were found to be higher in homozygotes of the protective allele of rs7731626. Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo-DC) differentiation as a process potentially influenced by MS risk SNPs.

A rare presentation of hepatolithiasis in an adolescent patient: A case report.

INTRODUCTION: Hepatolithiasis (intrahepatic stones) is rare in adolescent patients and requires complex management strategies to prevent recurrent infections and progression to hepatic fibrosis. Surgical management is often required. In cases of unclear etiology, further work-up is indicated to provide insight into future management. In this report we describe an extensive stone analysis. PRESENTATION OF CASE: A 20-year-old Caucasian female presented with known hepatolithiasis and multiple prior recurrent bouts of abdominal pain requiring hospitalization. Magnetic resonance cholangiopancreatography (MRCP) demonstrated an abnormal left-sided hepatic biliary ductal system dilatation. She was treated surgically with a formal left hepatectomy and preservation of the caudate lobe. The right ductal system had no stones or evidence of inflammation, and her bile and stones cultures were negative for organism growth. An extensive analysis demonstrated stone composition primarily of cholesterol. DISCUSSION: Adolescent presentations of hepatolithiasis are rare and considerations in the differential diagnosis include primary sclerosing cholangitis, bile acid transporter defects, and other known genetic diseases. This case is unique because only the left half of the intrahepatic ductal system had evidence of stone disease and the bile was sterile. A detailed stone analysis demonstrating cholesterol supersaturation provides additional context though the etiology remains unclear in this case and will require lifelong follow-up. CONCLUSION: Early-onset hepatolithiasis is rare and requires expert management, and in some cases definitive surgical management with life-long follow-up. Extensive stone analysis and genetic testing can be performed to help identify disease etiology in unique cases.

[Predictions of a SEIR model for COVID-19 cases in Cali-Colombia]. / Predicciones de un modelo SEIR para casos de COVID-19 en Cali, Colombia.

OBJECTIVE: To predict the number of cases of COVID-19 in the city of Cali-Colombia through the development of a SEIR model. METHODS: A SEIR compartmental deterministic model was used considering the states: susceptible (S), exposed (E), infected (I) and recovered (R). The model parameters were selected according to the literature review, in the case of the case fatality rate data from the Municipal Secretary of Health were used. Several scenarios were considered taking into account variations in the basic number of reproduction (R0), and the prediction until april 9 was compared with the observed data. RESULTS: Through the SEIR model it was found that with the highest basic number of reproduction [2,6] and using the case fatality rate for the city of 2,0%, the maximum number of cases would be reached on June 1 with 195 666 (prevalence). However, when comparing the observed with the expected cases, at the beginning the observed occurrence was above the projected, but then the trend changes decreasing the slope. CONCLUSIONS: SEIR epidemiological models are widely used methods for projecting cases in infectious diseases, however it must be taken into account that they are deterministic models that can use assumed parameters and could generate imprecise results.

[SARS-coV-2 spatio - temporal analysis in Cali, Colombia]. / Análisis espacio-temporal del SARS-COV-2 en Cali, Colombia.

OBJECTIVE: To describe the spatio-temporal distribution of the COVID-19 in the city of Cali during the first month of the epidemic. METHODS: An exploratory analysis of spatial data was carried out, consisting of a kernel density analysis and the presence of spatial patterns was verified by the K-Ripley function. RESULTS: The spatial distribution of the cases tends to initially concentrate in the north and south of the city, with a changing dynamic towards the east and west. CONCLUSIONS: The identified spatial pattern may be influenced by the isolation measures taken at the local and national level, but the effect of the low access of the general population to diagnostic tests, delays and restraints to know the results cannot be ruled out and even possible biases due to difficulties in the technique of taking the sample or its conservation.

Ectopic biomineralization in kidney stone formers compared to non-stone formers.

BACKGROUND: Kidney stone formers (SFs) are at increased risk of stroke, myocardial infarction, and atherosclerosis of the carotid and coronary arteries. These cardiovascular and urologic pathologies can result from ectopic biomineral deposition. The objectives of this study are: (I) to evaluate risk factors for ectopic biomineralization, and (II) to characterize the overall burden of ectopic minerals in known SFs compared to non-stone formers (NSFs) matched for these risk factors. METHODS: Presence and quantity of biominerals at eight anatomic locations (abdominal aorta, common iliac arteries, pelvic veins, prostate or uterus, mesentery, pancreas, and spleen) were determined in a case control study by retrospective analysis of clinical non-contrast computed tomography scans obtained from 190 SFs and 190 gender- and age-matched NSFs (renal transplant donors). Predictors of biomineralization were determined using negative binomial regression. A subgroup of 140 SFs and 140 NSFs were matched for risk factors for systemic biomineralization, and mineralization was compared between these matched SFs and NSFs using ordinal logistic regression. RESULTS: Hypertension, hyperlipidemia, diabetes mellitus, and smoking were more common amongst SFs. Risk factors for increased systemic biomineralization included history of nephrolithiasis, male gender, older age, and history of hyperlipidemia. When controlling for these comorbidities, SFs had significantly increased biomineralization systemically and at the abdominal aorta, iliac arteries, prostate, mesentery, pancreas, and spleen compared to NSFs. CONCLUSIONS: The current study provides evidence that SFs are at increased risk of biomineralization systemically, independent of common risk factors of atherosclerosis.

Use of GoFundMe® to crowdfund complementary and alternative medicine treatments for cancer.

PURPOSE: Complementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient's perspective for using CAM or declining conventional cancer therapy (CCT). METHODS: Five hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users. RESULTS: Compared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too "toxic" to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%). CONCLUSION: Cancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT.