Sex differences in murine myocutaneous flap revascularization.

Sex differences in susceptibility to ischemia/reperfusion injury have been documented in humans. Premenopausal women have a lower risk of ischemic heart disease than age-matched men, whereas after menopause, the risk is similar or even higher in women. However, little is known about the effects of sex on myocutaneous ischemia/reperfusion. To explore sex differences in wound revascularization, we utilized a murine myocutaneous flap model of graded ischemia. A cranial-based, peninsular-shaped, myocutaneous flap was surgically created on the dorsum of male and female mice. Physiological, pathological, immunohistochemical, and molecular parameters were analyzed. Flaps created on female mice were re-attached to the recipient site resulting in nearly complete viability at post-operative day 10. In contrast, distal full-thickness myocutaneous necrosis was evident at 10 days post-surgery in male mice. Over the 10 day study interval, laser speckle imaging documented functional revascularization in all flap regions in female mice, but minimal distal flap reperfusion in male mice. Day 10 immunostained histologic sections confirmed significant increases in distal flap vessel count and vascular surface area in female compared to male mice. RT-PCR demonstrated significant differences in growth factor and metabolic gene expression between female and male mice at day 10. In conclusion, in a graded-ischemia wound healing model, flap revascularization was more effective in female mice. The recognition and identification of sex-specific wound healing differences may lead to a better understanding of the underlying mechanisms of myocutaneous revascularization and drive novel discovery to improve soft tissue wound healing following tissue transfer for traumatic injury and cancer resection.

EBER-Negative, Double-Hit High-Grade B-Cell Lymphoma Responding to Methotrexate Discontinuation.

Background: First classified in 2016, high-grade B-cell lymphoma (HGBCL) is a lymphoid neoplasm that is typically seen as an aggressive lymphoproliferative disorder (LPD). In most patients with HGBCL, various oncogene rearrangements present with advanced clinical features, such as central nervous system involvement. Patients with underlying autoimmune and rheumatologic conditions, such as rheumatoid arthritis, are at higher risk for developing LPDs, including highly aggressive subtypes of non-Hodgkin lymphomas such as HGBCL. Case Presentation: We present a case of stage IV double-hit HGBCL with the presence of MYC and BCL6 gene rearrangements in an older veteran with rheumatoid arthritis treated with methotrexate. An excellent sustained response was observed for the patient's disease within 4 weeks of methotrexate discontinuation. To our knowledge, this is the first reported response to methotrexate discontinuation for a patient with HGBCL. Conclusions: Reducing immunosuppression should be considered in all patients with LPDs associated with autoimmune conditions or immunosuppressive medications, regardless of additional multiagent systemic therapy administration.

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.

BACKGROUND: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases. MATERIALS AND METHODS: We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial. RESULTS: CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC. CONCLUSION: To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.

Derivation and validation of a short emergency department screening tool for perpetrators of intimate partner violence: the PErpetrator RaPid Scale (PERPS).

BACKGROUND: There is no short screening tool for perpetrators of intimate partner violence (IPV), although one is needed. OBJECTIVE: To retrospectively derive and prospectively validate a brief screening tool for perpetrators of IPV: the PErpetration RaPid Scale (PERPS). METHODS: In the derivation phase of the study, we developed the PERPS based on historical data. The PERPS consists of three Yes/No questions about physical abuse of a partner. In the validation phase, we prospectively screened subjects during randomized 4-h shifts in a busy emergency department (ED). Subjects were asked to complete the newly derived three-question PERPS as well as the Physical Abuse of Partner Scale (PAPS), a 25-question Likert scale that is the gold standard for detection of physical abuse of a partner. The main outcome measures were sensitivity, specificity, predictive values, accuracy, and Cronbach alpha of the PERPS for internal consistency. RESULTS: The PERP Scale derivation was based on a 207-subject historical database, and resulted in a three-question PERPS. Validation was completed on a new set of 214 patients presenting to the ED during 52 randomized 4-h shifts. The prevalence of IPV perpetration using the PERPS was 47/207 (22.7%; 95% confidence interval [CI] 16-27). For the PAPS, prevalence was 56/207 (27%; 95% CI 20-32). Compared with the PAPS, the sensitivity of the PERPS was 66%, specificity 93%, negative predictive value 87%, positive predictive value 78%, with an accuracy of 85%. Cronbach alpha of the PERPS was 0.68. Age, gender, and race were not predictive of positive results on either scale. CONCLUSION: We successfully derived and validated a three-question perpetrator of IPV scale that can be used in a busy ED or office setting.

Adult intimate partner violence perpetrators are significantly more likely to have witnessed intimate partner violence as a child than nonperpetrators.

BACKGROUND: In a previous study, no association was found between intimate partner violence (IPV) victims and being an adult who witnessed IPV as a child (ACW). OBJECTIVE: The objective of the present study was to determine whether perpetrators of IPV (Perps) could be identified in a busy emergency department (ED) and whether Perps were more likely than non-Perps to be ACWs. The hypothesis was that Perps differed significantly from non-Perps in being ACWs, in being victims of IPV, and in demographics. METHODS: The design was a cross-sectional cohort of patients presenting to an academic ED during randomized 4-hour shifts. A choice of computer touch screen data vs paper format was offered. Data collected included demographics as well as scales to determine whether subjects were a Perp, victim, and/or ACW of IPV. Six validated scales were used to screen and confirm victims, Perps, and ACWs. Predictor variables were ACW, ongoing IPV, and demographics. RESULTS: Two hundred thirty-six subjects were entered, 207 had complete data sets. Forty-four (19%) were Perps. By univariate analysis, there was a significant correlation of Perps and ACW (P = .001 by single question) and between Perp and being victims (P = .001). No other univariate variables were significantly correlated. By regression analysis, significant predictors of Perp included ACW and spouse drug abuse. CONCLUSIONS: The Perps were identified in a busy ED setting. Perps were significantly more likely than non-Perps to be ACWs, but not more likely to be victims. Spouse drug abuse and ACW were the 2 significant predictors of Perp.

Hibernoma: diagnostic and surgical considerations of a rare benign tumour.

Hibernoma is a rare, benign tumour of brown fat origin. Less than 250 cases have been reported in the literature. We present a case of a 19-year-old man referred to surgical oncology for evaluation of a large soft tissue mass near the apex of his right scapula. Complete surgical excision was performed, sparing the overlying latissimus dorsi musculature. Surgical pathology revealed findings were consistent with hibernoma, grossly showing a well-encapsulated fluctuant mass measuring 21.4×14.4×5.3 cm, and histologically composed of brown fat adipocytes. The mainstay of treatment is surgical excision of the mass. Primary goals of the operation include complete removal of the mass to prevent recurrence and sparing of adjacent structures as it is a benign, non-invasive tumour. We present a case of a large chest wall hibernoma in a young adult, diagnosed on final pathology after complete surgical excision.

Management of splenic ectopic pregnancy presenting with massive haemoperitoneum.

Abdominal ectopic pregnancy (EP) accounts for only 1.3% of EPs and occurs when a fertilised ovum implants in an extrapelvic peritoneal location. Primary splenic pregnancy is a rare type of abdominal EP, with only 16 cases previously reported in the literature. Early diagnosis is essential as delay in treatment carries significant potential for morbidity and mortality. We present the case of a 27-year-old woman presenting with left upper quadrant abdominal pain, elevated human chorionic gonadotropin levels, absence of intrauterine gestational sac and massive haemoperitoneum on transvaginal ultrasound. The patient underwent emergent surgical exploration for high suspicion of ruptured abdominal EP. An open splenectomy was performed when the source of bleeding was confirmed to originate from the left upper quadrant. Final pathology confirmed subcapsular gestational sac implantation within the spleen. While two cases of medical management have been reported, splenectomy remains the current definitive management of rare cases of primary splenic pregnancy.

Myocutaneous revascularization following graded ischemia in lean and obese mice.

BACKGROUND: Murine models of diabetes and obesity have provided insight into the pathogenesis of impaired epithelialization of excisional skin wounds. However, knowledge of postischemic myocutaneous revascularization in these models is limited. MATERIALS AND METHODS: A myocutaneous flap was created on the dorsum of wild type (C57BL/6), genetically obese and diabetic (ob/ob, db/db), complementary heterozygous (ob+/ob-, db+/db-), and diet-induced obese (DIO) mice (n=48 total; five operative mice per strain and three unoperated mice per strain as controls). Flap perfusion was documented by laser speckle contrast imaging. Local gene expression in control and postoperative flap tissue specimens was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Image analysis of immunochemically stained histologic sections confirmed microvascular density and macrophage presence. RESULTS: Day 10 planimetric analysis revealed mean flap surface area necrosis values of 10.8%, 12.9%, 9.9%, 0.4%, 1.4%, and 23.0% for wild type, db+/db-, ob+/ob-, db/db, ob/ob, and DIO flaps, respectively. Over 10 days, laser speckle imaging documented increased perfusion at all time points with revascularization to supranormal perfusion in db/db and ob/ob flaps. In contrast, wild type, heterozygous, and DIO flaps displayed expected graded ischemia with failure of perfusion to return to baseline values. RT-PCR demonstrated statistically significant differences in angiogenic gene expression between lean and obese mice at baseline (unoperated) and at day 10. CONCLUSION: Unexpected increased baseline skin perfusion and augmented myocutaneous revascularization accompanied by a control proangiogenic transcriptional signature in genetically obese mice compared to DIO and lean mice are reported. In future research, laser speckle imaging has been planned to be utilized in order to correlate spatiotemporal wound reperfusion with changes in cell recruitment and gene expression to better understand the differences in wound microvascular biology in lean and obese states.

Narrowing the FOXF1 distant enhancer region on 16q24.1 critical for ACDMPV.

BACKGROUND: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal lung developmental disorder caused by heterozygous point mutations or genomic deletions involving FOXF1 or its 60-kb tissue-specific enhancer region mapping 270 kb upstream of FOXF1 and involving fetal lung-expressed long non-coding RNA genes and CpG-enriched sites. Recently, we have proposed that the FOXF1 locus at 16q24.1 may be a subject of genomic imprinting. FINDINGS: Using custom-designed aCGH and Sanger sequencing, we have identified a novel de novo 104 kb genomic deletion upstream of FOXF1 in a patient with histopathologically verified full phenotype of ACDMPV. This deletion allowed us to further narrow the FOXF1 enhancer region and identify its critical 15-kb core interval, essential for lung development. This interval harbors binding sites for lung-expressed transcription factors, including GATA3, ESR1, and YY1, and is flanked by the lncRNA genes and CpG islands. Bisulfite sequencing of one of these CpG islands on the non-deleted allele showed that it is predominantly methylated on the maternal chromosome 16. CONCLUSIONS: Substantial narrowing and bisulfite sequencing of the FOXF1 enhancer region on 16q24.1 provided new insights into its regulatory function and genomic imprinting.

Witnessing intimate partner violence as a child does not increase the likelihood of becoming an adult intimate partner violence victim.

OBJECTIVES: To determine whether adults who witnessed intimate partner violence (IPV) as children would have an increased rate of being victims of ongoing IPV, as measured by the Ongoing Violence Assessment Tool (OVAT), compared with adult controls who did not witness IPV as children. The authors also sought to determine whether there were differences in demographics in these two groups. METHODS: This was a cross sectional cohort study of patients presenting to a high-volume academic emergency department. Emergency department patients presenting from November 16, 2005, to January 5, 2006, during 46 randomized four-hour shifts were included. A confidential computer touch-screen data entry program was used for collecting demographic data, including witnessing IPV as a child and the OVAT. Main outcome measures were witnessing IPV as a child, ongoing IPV, and associated demographics. Assuming a prevalence of IPV of 20% and a clinically significant difference of 20% between adults who witnessed IPV as children and adult controls who did not witness IPV as children, the study was powered at 80%, with 215 subjects included. RESULTS: A total of 280 subjects were entered; 256 had complete data sets. Forty-nine percent of subjects were male, 45% were Hispanic, 72 (28%) were adults who witnessed IPV as children, and 184 (72%) were adult controls who did not witness IPV as children. Sixty-three (23.5%) were positive for ongoing IPV. There was no correlation of adults who witnessed IPV as children with the presence of ongoing IPV, as determined by univariate and bivariate analysis. Twenty-three of 72 (32%) of the adults who witnessed IPV as children, and 39 of 184 (21%) of the adult controls who did not witness IPV as children, were positive for IPV (difference, 11%; 95% confidence interval [CI] = -2% to 23%). Significant correlations with having witnessed IPV as a child included age younger than 40 years (odds ratio [OR], 4.2; 95% CI = 1.7 to 9.1), income less than $20,000/year (OR, 5.1; 95% CI = 1.6 to 12.5), and abuse as a child (OR, 9.1; 95% CI = 4.2 to 19.6). Other demographics were not significantly correlated with having witnessed IPV as a child. CONCLUSIONS: Adults who witnessed IPV as children were more likely to have a lower income, be younger, and have been abused as a child, but not more likely to be positive for ongoing IPV, when compared with patients who had not witnessed IPV.