A role for laparoscopy in the age of robotics: a retrospective cohort study of perioperative outcomes between 2D laparoscopic radical prostatectomy vs 3DHD laparoscopic radical prostatectomy.

PURPOSE: Our study compares perioperative outcomes between two-dimensional (2D) laparoscopic radical prostatectomy (LRP) and the 4th generation three-dimensional/high definition (3DHD) LRP. METHODS: Retrospectively acquired data from patients that underwent 2D LRP (n = 75) and 3DHD LRP (n = 75) from March 2013 to October 2015 were evaluated. Procedures were performed by a single surgeon. The extra-peritoneal approach with 5 trocars was utilized. Perioperative outcomes, potency, and continence were compared between groups. RESULTS: Patient characteristics were similar between the two groups in terms of age (p = 0.44), prostate-specific antigen (PSA) levels (p = 0.34), and Gleason scores (p = 0.14). Body mass index (BMI) was significantly higher in the 3DHD group (p = 0.0036). Postoperatively, no significant differences were observed in Hgb loss (p = 0.50), positive surgical margins (p = 1.00), and post-op Gleason scores (p = 0.30). Significant differences were observed for length of hospital stay (p < 0.001) and Jackson-Pratt (JP) drainage (p < 0.001). Regarding potency, 73.7% and 51.6% of the patients in the 3DHD and 2D groups regained potency at 6 months, respectively (p = 0.0025). Almost 43% of the patients in the 3DHD group regained continence at 1 month while for the 2D groups it was only 17.3% (p = 0.0008). CONCLUSION: 3DHD and 2D LRP have resulted in good outcomes in the perioperative periods. Our results show decreased JP drainage, shorter length of hospital stay, earlier return of urinary control, and earlier return of sexual function in the 3DHD LRP group. In lower volume centers where robotics equipment is not feasible due to economic barriers 3DHD can be safely performed as a minimally invasive alternative.

Team Science: Defining and Achieving Success.

Meghan Azad was the 2020 recipient of the CSCI Joe Doupe Young Investigator Award. Azad and Rodriguez co-direct a $14M research portfolio funded by the Canadian Institutes of Health Research, the Canadian Foundation for Innovation and the Bill and Melinda Gates Foundation. Spanning 45 countries, their acclaimed pediatric research is well known in clinical circles, highly cited by the scientific community and widely shared on mainstream and social media. In 2020, Azad was recognized among the WXN Top 100 Most Powerful Women in Canada and Rodriguez was named among the CBC Manitoba Future 40 Finalists. Here they share their Top 10 Tips for defining and achieving success in Team Science.

PARP Inhibition Synergizes with Melphalan but Does not Reverse Resistance Completely.

High-dose melphalan (MEL) and autologous stem cell transplantation (ASCT) is the standard of care in the treatment of multiple myeloma (MM). Resistance to MEL has been linked to increased DNA repair. Here we sought to identify whether inhibition of poly(ADP-ribose) polymerase (PARP) synergizes with MEL and can overcome resistance. We tested the synergistic cytotoxicity of 3 inhibitors of PARP (PARPi)-veliparib (VEL), olaparib (OLA), and niraparib (NIRA)-combined with MEL in RPMI8226 and U266 MM cell lines, as well as in their MEL resistance counterparts, RPMI8226-LR5 (LR5) and U266-LR6 (LR6). The addition of VEL, OLA, and NIRA to MEL reduced the half maximal inhibitory concentration (IC50) in RPMI8226 cells from 27.8 µM to 23.1 µM, 22.5 µM, and 18.0 µM, respectively. Similarly, the IC50 of MEL in U266 cells was decreased from 6.2 µM to 3.2 µM, 3.3 µM, and 3.0 µM, respectively. In LR5 and LR6 cells, PARPi did not reverse MEL resistance. We confirmed this in a NOD/SCID/gamma null xenograft mouse model with either MEL-sensitive (RPMI8226) or MEL-resistant (LR5) MM. Treatment with a MEL-VEL combination prolonged survival compared with MEL alone in RPMI8226 mice (107 days versus 67.5 days; P = .0009), but not in LR5 mice (41 versus 39 days; P = .09). We next tested whether 2 double-stranded DNA repair mechanisms, homologous recombination (HR) and nonhomologous end-joining (NHEJ), cause MEL resistance in LR5 and LR6 cells. In an HR assay, LR6 cells had a 4.5-fold greater HR capability than parent U226 cells (P = .05); however, LR5 cells had an equivalent HR ability as parent RPMI8226 cells. We hypothesized that NHEJ may be a mediator of MEL resistance in LR5 cells. Given that DNA-PK is integral to NHEJ and may be a therapeutic target, we treated LR5 cells with the DNA-PK inhibitor NU7026 in combination with MEL. Although NU7026 alone at 2.5 µM had no cytotoxicity, in combination it completely reversed resistance to MEL (MEL IC50, 46.4 µM versus 14.4 µM). We examined the clinical implications of our findings in a dataset of 414 patients treated with tandem ASCT. High PARP1 expressers had lower survival compared with patients with low expression (median 42.7 months versus median not reached; P = .003). We hypothesized that combined expression of the HR gene BRCA1, the NHEJ gene PRKDC (DNA-PK), and PARP1 may predict survival and found that overexpression of 0 (n = 101), 1 or 2 (n = 287), or all 3 (n = 26) genes had a negative impact on median survival (undefined versus 57.8 months versus 14.8 months; P < .0001). Here we demonstrate that PARPi synergized with MEL, but that resistance (which may be due to HR and NHEJ pathways) is not completely reversed by PARPi. In addition, we observed that a 3-gene analysis may be tested to identify patients resistant or sensitive to high-dose MEL.

Synergistic Cytotoxic Effect of Busulfan and the PARP Inhibitor Veliparib in Myeloproliferative Neoplasms.

Patients with high-risk myeloproliferative neoplasms (MPNs), and in particular myelofibrosis (MF), can be cured only with allogeneic hematopoietic stem cell transplantation (HSCT). Because MPNs and JAK2V617F-mutated cells show genomic instability, stalled replication forks, and baseline DNA double-strand breaks, DNA repair inhibition with poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors represents a potential novel therapy. Because the alkylating agent busulfan is integral in conditioning regimens for HSCT and leads to stalled replication forks through DNA strand cross-linking, we hypothesized that PARP inhibition with veliparib in combination with busulfan may lead to synergistic cytotoxicity in MPN cells. We first treated 2 MPN cell lines harboring the JAK2V617F mutation (SET2 and HEL) with veliparib at increasing concentrations and measured cell proliferation. SET2 and HEL cells were relatively sensitive to veliparib (IC50 of 11.3 µM and 74.2 µM, respectively). We next treated cells with increasing doses of busulfan in combination with 4 µM veliparib and found that the busulfan IC50 decreased from 27 µM to 4 µM in SET2 cells and from 45.1 µM to 28.1 µM in HEL cells. The mean combination index was .55 for SET2 cells and .40 for HEL cells. Combination treatment of SET2 cells caused G2M arrest in 53% of cells, compared with 30% with veliparib alone and 35% with busulfan alone. G2M arrest was associated with activation of the ATR-Chk1 pathway, as shown by an immunofluorescence assay for phosphorylated Chk1 (p-Chk1). We then tested in vivo the effect of combined low doses of busulfan and veliparib in a JAK2V617F MPN-AML xenotransplant model. Vehicle- and veliparib-treated mice had similar median survival of 39 and 40 days, respectively. Combination treatment increased median survival from 47 days (busulfan alone) to 50 days (P = .02). Finally, we tested the combined effect of busulfan and veliparib on CD34+ cells obtained from the bone marrow or peripheral blood of 5 patients with JAK2V617F-mutated and 2 patients with CALR-mutated MF. MF cells treated with the combination of veliparib and busulfan showed reduced colony formation compared with busulfan alone (87% versus 68%; P = .001). In contrast, treatment of normal CD34+ cells with veliparib did not affect colony growth. Here we show that in vivo confirmation that treatment with the PARP-1 inhibitor veliparib and busulfan results in synergistic cytotoxicity in MPN cells. Our data provide the rationale for testing novel pretransplantation conditioning regimens with combinations of PARP-1 inhibition and reduced doses of alkylators, such as busulfan and melphalan, for high-risk MPNs or MPN-derived acute myelogenous leukemia.

The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial.

BACKGROUND: Spinal anesthesia for cesarean delivery is associated with a high incidence of hypotension. Phenylephrine results in higher umbilical artery pH than ephedrine when used to prevent or treat hypotension in healthy women. We hypothesized that phenylephrine compared to ephedrine would result in higher umbilical artery pH in women with preeclampsia undergoing cesarean delivery with spinal anesthesia. METHODS: This study was a randomized double-blind clinical trial. Nonlaboring women with preeclampsia scheduled for cesarean delivery with spinal anesthesia at Prentice Women's Hospital of Northwestern Medicine were randomized to receive prophylactic infusions of phenylephrine or ephedrine titrated to maintain systolic blood pressure >80% of baseline. Spinal anesthesia consisted of hyperbaric 0.75% bupivacaine 12 mg, fentanyl 15 µg, and morphine 150 µg. The primary outcome was umbilical arterial blood pH and the secondary outcome was umbilical artery base excess. RESULTS: One hundred ten women were enrolled in the study and 54 per group were included in the analysis. There were 74 and 72 infants delivered in the ephedrine and phenylephrine groups, respectively. The phenylephrine:ephedrine ratio for umbilical artery pH was 1.002 (95% confidence interval [CI], 0.997-1.007). Mean [standard deviation] umbilical artery pH was not different between the ephedrine 7.20 [0.10] and phenylephrine 7.22 [0.07] groups (mean difference -0.02, 95% CI of the difference -0.06 to 0.07; P = .38). Median (first, third quartiles) umbilical artery base excess was -3.4 mEq/L (-5.7 to -2.0 mEq/L) in the ephedrine group and -2.8 mEq/L (-4.6 to -2.2mEq/L) in the phenylephrine group (difference -0.6 mEq/L, 95% CI of the difference -1.6 to 0.3 mEq/L; P = .10). When adjusted for gestational age and infant gender, umbilical artery pH did not differ between groups. There were also no differences in the umbilical artery pH stratified by magnesium therapy or by the severity of preeclampsia. CONCLUSIONS: We were unable to demonstrate a beneficial effect of phenylephrine on umbilical artery pH compared with ephedrine. Our findings suggest that phenylephrine may not have a clinically important advantage compared with ephedrine with regard to improved neonatal acid-base status when used to prevent spinal anesthesia-induced hypotension in women with preeclampsia undergoing cesarean delivery.

Collagenous gastritis with elevated fecal calprotectin in a pediatric patient.

Collagenous gastritis is a rare and chronic inflammatory condition of undetermined etiology characterized histologically by thickened subepithelial collagen bands and increased intraepithelial lymphocytes. Here, we present a collagenous gastritis case in a 16-year-old female with chronic abdominal pain, persistently elevated fecal calprotectin (507 and 796 mcg/g), and resolved iron deficiency anemia. The patient's history, laboratory tests, endoscopy, and magnetic resonance imaging ruled out common causes of elevated fecal calprotectin, including Helicobacter pylori and gastrointestinal infections, medications, celiac disease, and inflammatory bowel disease, as well as less common causes such as collagenous colitis. Esophagogastroduodenoscopy revealed significant antral nodularity. Gastric biopsies showed thickened subepithelial collagen band and surface epithelium damage with increased intraepithelial lymphocytes. The ileocolonoscopy was normal. This is among the first reported cases of collagenous gastritis with elevated fecal calprotectin levels that could solely be attributed to this condition.

Vascular Anastomoses and Dissection: A Six-Part Simulation Curriculum for Surgical Residents.

Introduction: As surgical technologies grow, so too do demands on surgical trainees to master increasing numbers of skill sets. With the rise of endovascular surgery, trainees have fewer opportunities to practice open vascular techniques in the operating room. Simulation can bridge this gap. However, existing published open vascular simulation curricula are basic or based on expensive models. Methods: We iteratively developed an open vascular skills curriculum for second-year surgery residents comprising six 2-hour sessions. We refined the curriculum based on feedback from learners and faculty. The curriculum required skilled facilitators, vascular instruments, and tissue models. We evaluated the latest iteration with a survey and by assessing participants' technical skills using the Objective Structured Assessment of Technical Skills (OSATS) form. Results: Over the past 10 years, 101 residents have participated in the curriculum. Nine of 13 residents who participated in the latest curricular iteration completed the survey. All respondents rated the sessions as excellent and strongly agreed that they had improved their abilities to perform anastomoses with tissue and prosthetic. Facilitators completed 18 OSATS forms for residents in the fifth and sixth sessions of the latest iteration. Residents scored well overall, with a median 26.5 (interquartile range: 24-29) out of a possible score of 35, with highest scores on knowledge of instruments. Discussion: This simulation-based curriculum facilitates open vascular surgical skill acquisition among surgery residents. The curriculum allows residents to acquire critical vascular skills that are challenging to learn in an increasingly demanding operative setting.

"Doing well": Intraoperative entrustable professional activity assessments provided limited technical feedback.

Background: Entrustable Professional Activities (EPAs) allow for the assessment of specific, observable, essential tasks in medical education. Since being developed in non-surgical fields, EPA assessments have been implemented in surgery to explore intraoperative entrustment. However, assessment burden is a significant problem for faculty, and it is unknown whether EPA assessments enable formative technical feedback. EPAs' formative utility could inform how surgical programs facilitate technical feedback for trainees. We aimed to assess the extent to which narrative comments provided through the Fellowship Council (FC) EPA assessments contained technical feedback. Methods: The FC previously collected EPA assessments for subspecialty surgical fellows from September 2020 to October 2022. Two raters reviewed assessments' narrative comments for inclusion of each skill area that makes up part of the Objective Structured Assessment of Technical Skills (OSATS). A third rater reconciled discrepant ratings. Results: During the study period, there were 3302 completed EPA assessments, including 1191 fellow self-assessments, 1124 faculty assessments, and 987 assessments without an identified assessor role. We found that assessments' narrative comments related to a median of two of the seven OSATS areas (IQR:1-2). There were no comments relevant to any of the seven OSATS areas in 16.0 % of all assessments. Conclusions: In this review of narrative comments for EPA assessments from the FC, we found that limited technical feedback of the kind included in the OSATS was provided in many assessments. These results suggest benefit to adjusting the EPA form, enhancing faculty development, or continuing additional types of targeted technical assessment intraoperatively. Key message: This analysis of narrative comments from fellowship EPA assessments showed that many assessments included limited technical feedback. To allow for continued technical feedback for fellows, these results highlight the need for further refinements of the EPA assessment form, additional faculty development, or ongoing use of other types of technical assessment.

A Case of Left Ventricular Pseudoaneurysm as a Complication of Late-Presenting ST-Segment Elevation Myocardial Infarction.

This case report delineates the clinical trajectory and management strategies of a 59-year-old Hispanic male diagnosed with a left ventricular pseudoaneurysm (LVPA) following a delayed presentation of ST-segment elevation myocardial infarction (STEMI), for which reperfusion treatment was not administered. Initially, an echocardiogram demonstrated an extensive anterolateral myocardial infarction, severe left ventricular systolic dysfunction, and an early-stage left ventricular apical aneurysm with thrombus, leading to the initiation of warfarin. Metabolic myocardial perfusion imaging via positron emission tomography indicated a substantial myocardial scar without viability, guiding the decision against revascularization. Post discharge, the patient, equipped with a wearable cardioverter defibrillator for sudden cardiac death prevention, experienced symptomatic ventricular tachycardia, which was resolved with defibrillator shocks. Subsequent imaging revealed an acute LVPA adjacent to the existing left ventricular aneurysm. Given the high surgical risk, conservative management was elected, resulting in thrombosis and closure of the pseudoaneurysm after two weeks. The patient eventually transitioned to home hospice, surviving an additional five months. This report underscores the complexities and therapeutic dilemmas in managing post-MI LVPA patients who are ineligible for surgical intervention.

Multimodal machine learning for modeling infant head circumference, mothers' milk composition, and their shared environment.

Links between human milk (HM) and infant development are poorly understood and often focus on individual HM components. Here we apply multi-modal predictive machine learning to study HM and head circumference (a proxy for brain development) among 1022 mother-infant dyads of the CHILD Cohort. We integrated HM data (19 oligosaccharides, 28 fatty acids, 3 hormones, 28 chemokines) with maternal and infant demographic, health, dietary and home environment data. Head circumference was significantly predictable at 3 and 12 months. Two of the most associated features were HM n3-polyunsaturated fatty acid C22:6n3 (docosahexaenoic acid, DHA; p = 9.6e-05) and maternal intake of fish (p = 4.1e-03), a key dietary source of DHA with established relationships to brain function. Thus, using a systems biology approach, we identified meaningful relationships between HM and brain development, which validates our statistical approach, gives credence to the novel associations we observed, and sets the foundation for further research with additional cohorts and HM analytes.

Human Milk Micronutrients and Child Growth and Body Composition in the First 2 years: A Systematic Review.

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly understood. We systematically searched MEDLINE, Embase, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m2)-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions.

Human Milk Macronutrients and Child Growth and Body Composition in the First Two Years: A Systematic Review.

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.

Human Milk Bioactive Components and Child Growth and Body Composition in the First 2 Years: A Systematic Review.

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

Home practice for robotic surgery: a randomized controlled trial of a low-cost simulation model.

Pre-operative simulated practice allows trainees to learn robotic surgery outside the operating room without risking patient safety. While simulation practice has shown efficacy, simulators are expensive and frequently inaccessible. Cruff (J Surg Educ 78(2): 379-381, 2021) described a low-cost simulation model to learn hand movements for robotic surgery. Our study evaluates whether practice with low-cost home simulation models can improve trainee performance on robotic surgery simulators. Home simulation kits were adapted from those described by Cruff (J Surg Educ 78(2): 379-381, 2021). Hand controllers were modified to mimic the master tool manipulators (MTMs) on the da Vinci Skills Simulator (dVSS). Medical students completed two da Vinci exercises: Sea Spikes 1 (SS1) and Big Dipper Needle Driving (BDND). They were subsequently assigned to either receive a home simulation kit or not. Students returned two weeks later and repeated SS1 and BDND. Overall score, economy of motion, time to completion, and penalty subtotal were collected, and analyses of covariance were performed. Semi-structured interviews assessed student perceptions of the robotic simulation experience. Thirty-three medical students entered the study. Twenty-nine completed both sessions. The difference in score improvement between the experimental and control groups was not significant. In interviews, students provided suggestions to increase fidelity and usefulness of low-cost robotic home simulation. Low-cost home simulation models did not improve student performance on dVSS after two weeks of at-home practice. Interview data highlighted areas to focus future simulation efforts. Ongoing work is necessary to develop low-cost solutions to facilitate practice for robotic surgery and foster more inclusive and accessible surgical education.

School Absenteeism as a Marker for Community COVID-19 Rates.

BACKGROUND: Reported community transmission rates of coronavirus disease 2019 (COVID-19) may not be accurate, particularly since at-home testing has become widely available. School absenteeism may serve as a marker of broader community COVID-19 transmission. METHODS: We performed an observational study of North Carolina kindergarten through 12th grade schools participating in the ABC Science Collaborative that offered in-school instruction, and contributed severe acute respiratory syndrome coronavirus 2 data for at least 2 of 4 weeks monthly for the 2021-2022 academic year. Additionally, we analyzed publicly available databases including the North Carolina Department of Public Instruction, Centers for Disease Control and Prevention COVID-19 Data Repository, and National Center for Education Statistics. We described community and school COVID-19 infection rates compared with student monthly absenteeism rates to determine if the relationship between community COVID-19 infection rates and student absenteeism varied over time. RESULTS: We included 500 192 students from 27 school districts. For the 2021-2022 academic year, the student and community COVID-19 infection rates did not show a significant difference (P > .05) across each month of comparison. Student absenteeism rates and community COVID-19 infection rates by month showed a similar trend across the academic year. For every 1% increase in community infection percentage, we found a 1.68% (1.12-2.25%) increase in absenteeism (P < .001); for every 1 month change in time, we found a 0.12% (0.01-0.24%) increase in absenteeism (P < .05). CONCLUSIONS: Student absenteeism and infection rates may be a useful marker of COVID-19 community infection rates when testing frequency and results reporting are inconsistent.

A Rare Skin Rash: Linezolid-Induced Purpuric Drug Eruption without Vasculitis in a Puerto Rican Man.

BACKGROUND Cutaneous adverse drug reactions are the skin's response to a systemic exposure to drugs. Linezolid is an oral oxazolidine used to treat methicillin-resistant Staphylococcus aureus infections. Even though it has well-known adverse effects, purpuric cutaneous adverse drug reactions to linezolid have been scarcely described. This report is of a Puerto Rican man in his 80s who developed an extensive purpuric drug eruption secondary to linezolid use. Clinicians should be aware of this phenomenon, since prompt identification and discontinuation of the agent are essential for recovery. CASE REPORT An 89-year-old Puerto Rican man was given oral linezolid therapy for healthcare-associated pneumonia and developed a widespread, purpuric cutaneous eruption 5 days into therapy. His condition prompted immediate discontinuation of the drug. Forty-eight hours after stopping the medication, he visited the Emergency Department. Abdominal punch biopsy revealed a superficial and perivascular lymphocytic infiltrate with dermal eosinophils, a pathologic finding consistent with a purpuric drug eruption. This allowed for a timely diagnosis, exclusion of other mimickers, such as cutaneous vasculitis, and effective management. CONCLUSIONS Cutaneous adverse drug reactions to linezolid have been scarcely reported in the literature. Due to the low incidence of this manifestation, the identification of the causative agent and accompanying treatment may be delayed. Mainstays in therapy are avoidance of the offending agent and treatment with corticosteroids, antihistamines, barrier ointments, and oral analgesics. Primary healthcare providers should be aware of linezolid-induced cutaneous manifestations, diagnostic clues, and treatment options so they can rapidly identify and effectively treat such complications.

Diagnosis and Management of a Massive Eight-Centimeter Acquired Tracheoesophageal Fistula.

Here, we present the case of a 61-year-old veteran Hispanic male with recurrent aspiration pneumonitis, aerophagia, tympanic abdominal bloating, and a positive Ono's sign; symptoms present were secondary to diagnosed tracheoesophageal fistulas (TEFs). TEFs are abnormal connections between the esophagus and the trachea. In adult cases, several risk factors have been identified for acquired cases, which include infection, trauma, and cancer. Diagnosis of TEF can be challenging and, in most cases, requires high suspicion. Currently, there are no established guidelines for diagnosing and managing TEF. Clinical assessment and various imaging techniques are essential in the diagnostic process. This article will discuss the etiology, clinical presentation, diagnostic approaches, and management options for acquired TEFs.

Evaluation of AIML + HDR-A Course to Enhance Data Science Workforce Capacity for Hispanic Biomedical Researchers.

Artificial intelligence (AI) and machine learning (ML) facilitate the creation of revolutionary medical techniques. Unfortunately, biases in current AI and ML approaches are perpetuating minority health inequity. One of the strategies to solve this problem is training a diverse workforce. For this reason, we created the course "Artificial Intelligence and Machine Learning applied to Health Disparities Research (AIML + HDR)" which applied general Data Science (DS) approaches to health disparities research with an emphasis on Hispanic populations. Some technical topics covered included the Jupyter Notebook Framework, coding with R and Python to manipulate data, and ML libraries to create predictive models. Some health disparities topics covered included Electronic Health Records, Social Determinants of Health, and Bias in Data. As a result, the course was taught to 34 selected Hispanic participants and evaluated by a survey on a Likert scale (0-4). The surveys showed high satisfaction (more than 80% of participants agreed) regarding the course organization, activities, and covered topics. The students strongly agreed that the activities were relevant to the course and promoted their learning (3.71 ± 0.21). The students strongly agreed that the course was helpful for their professional development (3.76 ± 0.18). The open question was quantitatively analyzed and showed that seventy-five percent of the comments received from the participants confirmed their great satisfaction.

Cohort profile: investigating SARS-CoV-2 infection and the health and psychosocial impact of the COVID-19 pandemic in the Canadian CHILD Cohort.

The coronavirus disease 2019 (COVID-19) pandemic has affected all Canadian families, with some impacted differently than others. Our study aims to: (1) determine the prevalence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Canadian families, (2) identify predictors of infection susceptibility and severity of SARS-CoV-2, and (3) identify health and psychosocial impacts of the COVID-19 pandemic. This study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3,454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009 and 2012. During the pandemic, CHILD households were invited to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure and testing, vaccination status, physical and mental health, and pandemic-driven life changes; and (3) in-home biological sampling kits to collect blood and stool. In total, 1,462 households (5,378 participants) consented to the CHILD COVID-19 Add-On Study: 2,803 children (mean±standard deviation [SD], 9.0±2.7 years; range, 0-17 years) and 2,576 adults (mean±SD, 43.0±6.5 years; range, 18-85 years). We will leverage the wealth of pre-pandemic CHILD data to identify risk and resilience factors for susceptibility and severity to the direct and indirect pandemic effects. Our short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.

Response of the G2-prophase checkpoint to genotoxic drugs in lymphocytes from healthy individuals.

We analyzed the in vitro effects of the anti-tumoral drugs doxorubicin, cytosine arabinoside and hydroxyurea on the G2-prophase checkpoint in lymphocytes from healthy individuals. At biologically equivalent concentrations, the induced DNA damage activated the corresponding checkpoint. Thus: i) there was a concentration-dependent delay of G2 time and an increase of both the total DNA lesions produced and repaired before metaphase and; ii) G2-checkpoint adaptation took place as chromosome aberrations (CAs) started to appear in the metaphase, indicating the presence of unrepaired double-strand breaks (DSBs) in the previous G2. The checkpoint ATM/ATR kinases are involved in DSB repair, since the recorded frequency of CAs increased when both kinases were caffeine-abrogated. In genotoxic-treated cells about three-fold higher repair activity was observed in relation to the endogenous background level of DNA lesions. The maximum rate of DNA repaired was 3.4 CAs/100 metaphases/hour, this rise being accompanied by a modest 1.3 fold lengthening of late G2 prophase timing. Because of mitotic chromosome condensation, no DSBs repair can take place until the G1 phase of the next cell cycle, when it occurs by DNA non-homologous end joining (NHEJ). Chromosomal rearrangements formed as a consequence of these error-prone DSB repairs ensure the development of genome instability through the DNA-fusion-bridge cycle. Hence, adaptation of the G2 checkpoint supports the appearance of secondary neoplasia in patients pretreated with genotoxic drugs.