Intestinal Spirochetosis: To Treat or Not to Treat.

Spirochete colonization of the gastrointestinal tract is a poorly understood phenomenon presenting with varying signs and symptoms. Due to the lack of a unified approach and its varying presentations, the management decision for intestinal spirochetosis (IS) has always been challenging. While metronidazole is the commonly preferred antimicrobial treatment, it remains unclear if therapeutic intervention is indicated for everyone, especially asymptomatic patients. We present three patients, diagnosed with IS. They presented with varying demographics, clinical presentations, and past medical histories and underwent different clinical managements. Our decisions for treatment not only included presenting symptoms but also factors like history of pre-existing gastrointestinal diseases, age, and immune status.

Risk of colorectal cancer in patients with primary sclerosing cholangitis and concomitant inflammatory bowel disease compared with primary sclerosing cholangitis only.

AIM: Primary sclerosing cholangitis (PSC) increases the risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients; however, there is a paucity of literature to suggest PSC alone as an independent risk factor for CRC. We aimed to determine if PSC is an independent risk factor for CRC in a large tertiary care medical center. Optimizing screening intervals is of great importance, given the burden and risks associated with a lifetime of colonoscopy screening. METHODS: This retrospective cohort study consists of patients diagnosed with PSC preceding IBD (PSC-IBD) and PSC-only before January 6, 2023 from a large, tertiary, academic medical center. Patients diagnosed with IBD concurrently or before PSC were excluded to reduce IBD's impact on CRC risk. Demographic data and colonoscopy findings were collected and assessed. RESULTS: Overall, 140 patients from all NYU Langone Health clinical settings were included. Patients with PSC-IBD were more likely to be diagnosed with CRC (23.3% vs. 1.8%, p < 0.01) and either low-grade or uncharacterized dysplasia (16.7% vs. 0.0%, p < 0.01) compared with those with PSC-only. Among PSC-only patients, the estimated CRC risk was significantly elevated compared with that expected of the standard NYU Langone population (SIR 9.2, 95% CI 1.1, 33.2). CONCLUSIONS: Our study revealed a significantly heightened CRC risk in PSC-IBD patients compared with those with PSC-only. Importantly, individuals with PSC-only also face a greater CRC risk compared with the general population. Individuals with PSC-alone may require extended screening and surveillance colonoscopy intervals compared with those with PSC-IBD, yet still require more frequent monitoring than screening guidelines recommend for the general population.

Role of cytoreduction and hyperthermic intraperitoneal chemotherapy for metastatic gastroesophageal junction adenocarcinoma?

Gastric cancer is the fifth most prevalent cancer worldwide and the third leading cause of cancer- related mortality. Peritoneal carcinomatosis can develop in patients with a primary gastric tumor in a substantial proportion of patients, with estimates ranging from 14% to 43%. For patients with peritoneal carcinomatosis from gastric cancer, therapeutic options are limited. Intraperitoneal chemotherapy, combined with hyperthermia (HIPEC), provides regional dose intensification within the peritoneal cavity, effectively targeting peritoneal carcinomatosis with minimal systemic exposure. We report a case of gastroesophageal junction adenocarcinoma with peritoneal metastasis successfully treated with of cytoreductive surgery and HIPEC, and followed by surgery and systemic chemotherapy, highlighting HIPEC as one of the viable options and the importance of a multimodal approach for the treatment of this case.

Racial Disparities in Hospitalization Rates During Long-Term Follow-Up After Deceased-Donor Kidney Transplantation.

OBJECTIVE: To compare hospitalization rates between African American (AA) and European American (EA) deceased-donor (DD) kidney transplant (KT) recipients during over a10-year period. METHOD: Data from the Scientific Registry of Transplant Recipients and social determinants of health (SDoH), measured by the Social Deprivation Index, were used. Hospitalization rates were estimated for kidney recipients from AA and EA DDs who had one kidney transplanted into an AA and one into an EA, leading to four donor/recipient pairs (DRPs): AA/AA, AA/EA, EA/AA, and EA/EA. Poisson-Gamma models were fitted to assess post-transplant hospitalizations. RESULT: Unadjusted hospitalization rates (95% confidence interval) were higher among all DRP involving AA, 131.1 (122.5, 140.3), 134.8 (126.3, 143.8), and 102.4 (98.9, 106.0) for AA/AA, AA/EA, and EA/AA, respectively, compared to 97.1 (93.7, 100.6) per 1000 post-transplant person-years for EA/EA pairs. Multivariable analysis showed u-shaped relationships across SDoH levels within each DRP, but findings varied depending on recipients' race, i.e., AA recipients in areas with the worst SDoH had higher hospitalization rates. However, EA recipients in areas with the best SDoH had higher hospitalization rates than their counterparts. CONCLUSIONS: Relationship between healthcare utilization and SDoH depends on DRP, with higher hospitalization rates among AA recipients living in areas with the worst SDoH and among EA recipients in areas with the best SDoH profiles. SDoH plays an important role in driving disparities in hospitalizations after kidney transplantation.

Incidental aortocaval fistula in the setting of an unruptured abdominal aortic aneurysm.

An aortocaval fistula, a rare abnormal vascular communication between the aorta and inferior vena cava, is most commonly associated with abdominal aortic aneurysms (AAAs). Other factors leading to aortocaval fistula formation include atherosclerosis, collagen vascular diseases, vasculitis, hematogenous infections, prior spinal surgery, malignancy and radiation exposure. In rare instances, aortocaval fistulas may be discovered incidentally on abdominal imaging. We report an unusual case of an incidental aortocaval fistula in a 93-year-old male patient with an unruptured AAA, presenting with shortness of breath, malaise and lethargy. The patient had no other obvious risk factors for aortocaval fistula formation. Multidetector computed tomography angiography helped identify the fistula, and the patient was eventually transferred to hospice for comfort measures. This case highlights the importance of detailed imaging and preoperative planning in managing aortocaval fistulas and associated AAAs.

Digitally Disconnected: Qualitative Study of Patient Perspectives on the Digital Divide and Potential Solutions.

BACKGROUND: As telemedicine utilization increased during the COVID-19 pandemic, divergent usage patterns for video and audio-only telephone visits emerged. Older, low-income, minority, and non-English speaking Medicaid patients are at highest risk of experiencing technology access and digital literacy barriers. This raises concern for disparities in health care access and widening of the "digital divide," the separation of those with technological access and knowledge and those without. While studies demonstrate correlation between racial and socioeconomic demographics and technological access and ability, individual patients' perspectives of the divide and its impacts remain unclear. OBJECTIVE: We aimed to interview patients to understand their perspectives on (1) the definition, causes, and impact of the digital divide; (2) whose responsibility it is to address this divide, and (3) potential solutions to mitigate the digital divide. METHODS: Between December 2020 and March 2021, we conducted 54 semistructured telephone interviews with adult patients and parents of pediatric patients who had virtual visits (phone, video, or both) between March and September 2020 at the University of Chicago Medical Center (UCMC) primary care clinics. A grounded theory approach was used to analyze interview data. RESULTS: Patients were keenly aware of the digital divide and described impacts beyond health care, including employment, education, community and social contexts, and personal economic stability. Patients described that individuals, government, libraries, schools, health care organizations, and even private businesses all shared the responsibility to address the divide. Proposed solutions to address the divide included conducting community technology needs assessments and improving technology access, literacy training, and resource awareness. Recognizing that some individuals will never cross the divide, patients also emphasized continued support of low-tech communication methods and health care delivery to prevent widening of the digital divide. Furthermore, patients viewed technology access and literacy as drivers of the social determinants of health (SDOH), profoundly influencing how SDOH function to worsen or improve health disparities. CONCLUSIONS: Patient perspectives provide valuable insight into the digital divide and can inform solutions to mitigate health and resulting societal inequities. Future work is needed to understand the digital needs of disconnected individuals and communities. As clinical care and delivery continue to integrate telehealth, studies are needed to explore whether having a video or audio-only phone visit results in different patient outcomes and utilization. Advocacy efforts to disseminate public and private resources can also expand device and broadband internet access, improve technology literacy, and increase funding to support both high- and low-tech forms of health care delivery for the disconnected.

Spatiotemporal dynamics of γH2AX in the mouse brain after acute irradiation at different postnatal days with special reference to the dentate gyrus of the hippocampus.

Gamma H2A histone family member X (γH2AX) is a molecular marker of aging and disease. However, radiosensitivity of the different brain cells, including neurons, glial cells, cells in cerebrovascular system, epithelial cells in pia mater, ependymal cells lining the ventricles of the brain in immature animals at different postnatal days remains unknown. Whether radiation-induced γH2AX foci in immature brain persist in adult animals still needs to be investigated. Hence, using a mouse model, we showed an extensive postnatal age-dependent induction of γH2AX foci in different brain regions at 1 day after whole body gamma irradiation with 5Gy at postnatal day 3 (P3), P10 and P21. P3 mouse brain epithelial cells in pia mater, glial cells in white matter and cells in cerebrovascular system were more radiosensitive at one day after radiation exposure than those from P10 and P21 mice. Persistent DNA damage foci (PDDF) were consistently demonstrated in the brain at 120 days and 15 months after irradiation at P3, P10 and P21, and these mice had shortened lifespan compared to the age-matched control. Our results suggest that early life irradiation-induced PDDF at later stages of animal life may be related to the brain aging and shortened life expectancy of irradiated animals.

Mother-child histocompatibility and risk of rheumatoid arthritis and systemic lupus erythematosus among mothers.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags). We created a variable of exposure to histocompatible children. We estimated an average sequence similarity matching (SSM) score for each mother based on discordant mother-child alleles as a measure of histocompatibility. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals. A total of 138 RA, 117 SLE, and 913 control mothers were analyzed. Increased risk of RA was associated with having any child compatible at HLA-B (OR 1.9; 1.2-3.1), DPB1 (OR 1.8; 1.2-2.6) or DQB1 (OR 1.8; 1.2-2.7). Compatibility at mHag ZAPHIR was associated with reduced risk of SLE among mothers carrying the HLA-restriction allele B*07:02 (n = 262; OR 0.4; 0.2-0.8). Our findings support the hypothesis that mother-child histocompatibility is associated with risk of RA and SLE.

Differences in macular capillary parameters between healthy black and white subjects with Optical Coherence Tomography Angiography (OCTA).

PURPOSE: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). METHODS: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. RESULTS: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). CONCLUSION: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR.

Increased risk of rheumatoid arthritis among mothers with children who carry DRB1 risk-associated alleles.

OBJECTIVE: To investigate whether a child's genotype affects a mother's risk of rheumatoid arthritis (RA) beyond the risk associated with her genotype and to test whether exposure to fetal alleles inherited from the father increases risk of RA among mothers without risk alleles. METHODS: A case-control study was conducted among 1165 mothers (170 cases/995 controls) and their respective 1482 children. We tested the association between having any child with alleles encoding amino acids (AAs) associated with RA including the 'shared epitope' (SE) and DERAA AA sequences at positions 70-74; AA valine, lysine and alanine at positions 11, 71 and 74 of HLA-DRB1; aspartic acid at position 9 of HLA-B and phenylalanine at position 9 of DPB1. We used logistic regression models to estimate OR and 95% CI for each group of alleles, adjusting for maternal genotype and number of live births. RESULTS: We found increased risk of RA among mothers who had any child with SE (OR 3.0; 95% CI 2.0 to 4.6); DERAA (OR 1.7; 95% CI 1.1 to 2.6); or valine (OR 2.3; 95% CI 1.6 to 3.5), lysine (OR 2.3; 95% CI 1.5 to 3.4) and alanine (OR 2.8; 95% CI 1.2 to 6.4) at DRB1 positions 11, 71 and 74, respectively. Among non-carrier mothers, increased risk of RA was associated with having children who carried DERAA (OR 1.7; 95% CI 1.0 to 2.7) and alleles encoding lysine at DRB1 position 71 (OR 2.3; 95% CI 1.5 to 4.8). CONCLUSION: Findings support the hypothesis that a child's genotype can contribute independently to risk of RA among mothers.

Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism. Platelet Function Analyzer 100 and Plateletworks may be useful for confirming clopidogrel treatment in these cats.

A Child's HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE.

Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests.

The objectives of this study were to establish feline references intervals for 3 commercial whole blood platelet function test analyzer systems: Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario, Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX). Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95% confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89) sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using flow cytometry hematology analyzer platelet counts. There were low correlations between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; ρ = 0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist using impedance platelet counts; ρ = 0.14). The PW assay percent aggregations using impedance and flow cytometric platelet counts were correlated for both ADP (ρ = 0.64) and COL (ρ = 0.64) agonists. Platelet function testing using these tests are feasible in cats, but 95% CIs are wide, so single results may be difficult to interpret. Platelet counting by impedance or flow cytometry may be used for the PW assay but are not interchangeable.

Virulence of plant pathogenic bacteria attenuated by degradation of fatty acid cell-to-cell signaling factors.

Diffusible signal factor (DSF) is a fatty acid signal molecule involved in regulation of virulence in several Xanthomonas species as well as Xylella fastidiosa. In this study, we identified a variety of bacteria that could disrupt DSF-mediated induction of virulence factors in Xanthomonas campestris pv. campestris. While many bacteria had the ability to degrade DSF, several bacterial strains belonging to genera Bacillus, Paenibacillus, Microbacterium, Staphylococcus, and Pseudomonas were identified that were capable of particularly rapid degradation of DSF. The molecular determinants for rapid degradation of DSF in Pseudomonas spp. strain G were elucidated. Random transposon mutants of strain G lacking the ability to degrade DSF were isolated. Cloning and characterization of disrupted genes in these strains revealed that carAB, required for the synthesis of carbamoylphosphate, a precursor for pyrimidine and arginine biosynthesis is required for rapid degradation of DSF in strain G. Complementation of carAB mutants restored both pyrimidine prototrophy and DSF degradation ability of the strain G mutant. An Escherichia coli strain harboring carAB of Pseudomonas spp. strain G degrades DSF more rapidly than the parental strain, and overexpression of carAB in trans increased the ability of Pseudomonas spp. strain G to degrade as compared with the parental strain. Coinoculation of X. campestris pv. campestris with DSF-degrading bacteria into mustard and cabbage leaves reduced disease severity up to twofold compared with plants inoculated only with the pathogen. Likewise, disease incidence and severity in grape stems coinoculated with Xylella fastidiosa and DSF-degrading strains were significantly reduced compared with plants inoculated with the pathogen alone. Coinoculation of grape plants with a carAB mutant of Pseudomonas spp. strain G complemented with carAB in trans reduced disease severity as well or better than the parental strain. These results indicate that overexpression of carAB in other endophytes could be a useful strategy of biocontrol for the control of diseases caused by plant pathogens that produce DSF.

Production of the antimalarial drug precursor artemisinic acid in engineered yeast.

Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is highly effective against multi-drug-resistant Plasmodium spp., but is in short supply and unaffordable to most malaria sufferers. Although total synthesis of artemisinin is difficult and costly, the semi-synthesis of artemisinin or any derivative from microbially sourced artemisinic acid, its immediate precursor, could be a cost-effective, environmentally friendly, high-quality and reliable source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is transported out and retained on the outside of the engineered yeast, meaning that a simple and inexpensive purification process can be used to obtain the desired product. Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.