Recognition and Treatment of Wounds in Persons Using Xylazine: A Case Report From New Haven, Connecticut.

BACKGROUND: Xylazine is an α 2 -adrenergic agonist that is commonly used as a veterinary tranquilizer and is increasingly present in the unregulated US drug supply since at least 2019. There are many suspected clinical complications of xylazine use, including unusual skin wounds, atypical overdose presentations, and possible dependence and withdrawal syndromes. However, there are few reports of cutaneous manifestations of xylazine in patients who inject drugs that can guide diagnosis and management in patients with confirmed xylazine toxicology. CASE SUMMARY: We present the cases of 3 stably housed patients in Connecticut with opioid use disorder and intravenous use of fentanyl who presented with atypical, chronic wounds at the site of injection drug use. Xylazine toxicology sent on all 3 patients was positive. All patients were seen by wound care and dermatology, and 1 patient was followed by infectious diseases. Wound care management strategies are discussed as well as harm reduction strategies. For all patients, the dose of their medication for opioid use disorder was increased to decrease frequency of drug use given concern that patients were exposed to a drug supply containing xylazine. CLINICAL SIGNIFICANCE: This case report presents wound characteristics that raise the index of suspicion for xylazine-involved injection wounds and might assist in their diagnosis and management. There is urgent need for more reporting of such cases as well as rigorous research to understand the potential impact of xylazine on people who use drugs. Multidisciplinary best practices should be established.

The utility of magnetic resonance imaging in early-stage breast cancer survivors-An institutional experience and literature review.

The role of breast magnetic resonance imaging (MRI) in the screening of breast cancer survivors with remaining breast tissue is not well studied. We sought to evaluate the outcomes of screening breast MRI in a cohort of breast cancer survivors. A population of patients with history of stage I-IIIa breast cancer and ≥1 MRI a year or later from diagnosis between 2006-2008 were identified using the National Comprehensive Cancer Network data base from two large Boston-area cancer centers. Patient and disease characteristics were obtained from the data base, and medical records were reviewed to identify the index MRI (first eligible), indications, and two-year outcomes. Overall, 647 patients had breast MRI scans during the study period including 342 eligible patients whose index MRIs were done for breast screening purposes. 47/342 (13.7%) were abnormal, and 3.8% (13/342) underwent biopsy, resulting in the detection of 3 cases of locoregional recurrence or new primary breast cancer (0.9%, 95% CI = 0.2%-2.5%). Of 295 patients with a normal index screening MRI, 12 had a breast cancer recurrence diagnosed within 2 years (4.1% 95%CI = 2.1%-7.0%), and 5 of these recurrences were limited to MRI-screened breast tissue. No statistically significant difference in the rate of 2-year locoregional or distant recurrence was observed between patients with an abnormal screening MRI and those with a normal scan. Adjunct single breast MRI surveillance in a general population of breast cancer survivors one year after diagnosis detected few recurrences, and its effect on short-term outcomes was unclear.

Correction: Evaluation of significant genome-wide association studies risk-SNPs in young breast cancer patients.

[This corrects the article DOI: 10.1371/journal.pone.0216997.].

Evaluation of significant genome-wide association studies risk - SNPs in young breast cancer patients.

PURPOSE: Genome-wide-association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. Most of these studies were conducted primarily in postmenopausal breast cancer patients. Therefore, we set out to assess whether or not these breast cancer variants are also associated with an elevated risk of breast cancer in young premenopausal patients. METHODS: In 451 women of European ancestry who had prospectively enrolled in a longitudinal cohort study for women diagnosed with breast cancer at or under age 40, we genotyped 44 SNPs that were previously associated with breast cancer risk. A control group was comprised of 1142 postmenopausal healthy women from the Nurses' Health Study (NHS). We assessed if the frequencies of the adequately genotyped SNPs differed significantly (p≤0.05) between the cohort of young breast cancer patients and postmenopausal controls, and then we corrected for multiple testing. RESULTS: Genotyping of the controls or cases was inadequate for comparisons between the groups for seven of the 44 SNPs. 9 of the remaining 37 were associated with breast cancer risk in young women with a p-value <0.05: rs10510102, rs1219648, rs13387042, rs1876206, rs2936870, rs2981579, rs3734805, rs3803662 and rs4973768. The directions of these associations were consistent with those in postmenopausal women. However, after correction for multiple testing (Benjamini Hochberg) none of the results remained statistically significant. CONCLUSION: After correction for multiple testing, none of the alleles for postmenopausal breast cancer were clearly associated with risk of premenopausal breast cancer in this relatively small study.

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. METHODS: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. RESULTS: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. CONCLUSIONS: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.

Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells.

Two populations of Nkx2-1(+) progenitors in the developing foregut endoderm give rise to the entire postnatal lung and thyroid epithelium, but little is known about these cells because they are difficult to isolate in a pure form. We demonstrate here the purification and directed differentiation of primordial lung and thyroid progenitors derived from mouse embryonic stem cells (ESCs). Inhibition of TGFß and BMP signaling, followed by combinatorial stimulation of BMP and FGF signaling, can specify these cells efficiently from definitive endodermal precursors. When derived using Nkx2-1(GFP) knockin reporter ESCs, these progenitors can be purified for expansion in culture and have a transcriptome that overlaps with developing lung epithelium. Upon induction, they can express a broad repertoire of markers indicative of lung and thyroid lineages and can recellularize a 3D lung tissue scaffold. Thus, we have derived a pure population of progenitors able to recapitulate the developmental milestones of lung/thyroid development.