RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor.

We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light- and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies.

Evaluation of Patient Expectations and Outcomes after Distal Radius Fractures.

BACKGROUND: Patient expectations influence patient-reported outcomes after musculoskeletal injuries. The goal of this study is to determine how pretreatment expectations correlate with outcomes in patients with distal radius fractures. METHODS: Seventy-five patients with an isolated distal radius fracture were prospectively enrolled into nonoperative and operative cohorts. The Trauma Expectation Factor-Trauma Outcome Measure (TEF-TOM) score was the primary outcome measure. Trauma Expectation Factor scores were recorded at the time of enrollment, and TOM scores were recorded at 3, 6, and 12 months. Quick Disabilities of the Arm, Shoulder, and Hand (qDASH) and Patient-Rated Wrist Evaluation (PRWE) scores were also recorded. RESULTS: Trauma Outcome Measure scores at all time points were worse than expected (P < .01). Expectations were higher for patients younger than 65 years than for the 65+ group (P = .02). In patients aged 65+ years, mean TOM at 3 months was not significantly different than expected (P = .11) but decreased by 6 (P = .04) and 12 months (P < .01). Baseline TEF and TEF-TOM scores were not significantly different between operative and nonoperative groups (P = .37). Quick Disabilities of the Arm, Shoulder, and Hand and PRWE scores were not significantly different between age or treatment groups at the final follow-up. CONCLUSIONS: The overall treatment of distal radial injuries in our study did not meet patient expectations. Patients aged 65 years or older had lower expectations but were not able to predict their outcomes better than patients aged <65 years. There were no differences in TEF or TOM by treatment method. Patients demonstrated improved functional outcomes (qDASH/PRWE) at all time points regardless of age and treatment method.

Providing a post-vasectomy semen analysis cup at the time of vasectomy rather than post-operatively improves compliance.

Background: Post-vasectomy semen analysis (PVSA) completion rates after vasectomy are poor, and minimizing the need for an additional in-person visit may improve compliance. We hypothesized that providing PVSA specimen cup at time of vasectomy instead of at a postoperative appointment might be associated with higher PVSA completion rates. Methods: We performed a retrospective cohort study with historical control using medical records of all patients seen by a single provider for vasectomy consultation between October 2016 and June 2022. All patients who underwent vasectomy were included. Patients who underwent vasectomy prior to 05/01/2020 had PVSA specimen cup given at postoperative appointment two weeks following vasectomy, and those who underwent vasectomy after 05/01/2020 were given PVSA specimen cup at time of vasectomy. PVSA completion, demographic, and clinical outcomes data were collected. Logistic regressions were used to investigate associations between PVSA completion rates and timing of PVSA specimen cup provision. Results: There were no significant differences among study cohorts across all patient demographics analyzed, including age, body mass index (BMI), age of primary partner, presence of children, and history of prior genitourinary infection. A total of 491 patients were seen for vasectomy consultation between October 2016 and June 2022; among these patients, 370 underwent vasectomy. Of these, 173 (46.8%) patients underwent vasectomy prior to 05/01/2020 and were given PVSA specimen cup at postoperative visit; 197 (53.2%) patients underwent vasectomy after 05/01/2020 and were given PVSA specimen cup at vasectomy. Providing PVSA specimen cup at time of vasectomy was associated with higher odds of PVSA completion than providing PVSA specimen cup at postoperative visit [62.4% vs. 49.7%; odds ratio (OR) =1.68; 95% confidence interval (CI): 1.11, 2.55]. Adjusting for all identified confounders excludes 35 (9.5%) patients without a primary partner and shows no statistically significant association in cup timing [adjusted OR (aOR) =1.53; 95% CI: 0.98, 2.39]. Adjusting for all identified confounders except age of primary partner revealed timing of specimen cup provision at time of vasectomy was associated with higher odds of PVSA completion (aOR =1.64; 95% CI: 1.08, 2.52). Conclusions: PVSA specimen cup provision at time of vasectomy versus at postoperative appointment is associated with higher rates of PVSA completion in this retrospective cohort study.

Comparison of Intramedullary Screw Fixation, Plating, and K-Wires for Metacarpal Fracture Fixation: A Meta-Analysis.

BACKGROUND: Metacarpal fractures are common injuries with multiple options for fixation. Our purpose was to compare outcomes in metacarpal fractures treated with intramedullary screw fixation (IMF), Kirschner wires (K-wires), or plating. METHODS: A systematic literature review using the MEDLINE database was performed for studies investigating metacarpal fractures treated with IMF, plating, or K-wires. We identified 34 studies (9 IMF, 8 plating, 17 K-wires). A meta-analysis using both mixed and fixed effects models was performed. Outcome measures included mean Disabilities of the Arm, Shoulder, and Hand (DASH) scores, total active motion (TAM), grip strength, time to radiographic healing, and rates of infection and reoperation. RESULTS: Patients with IMF had significantly lower DASH scores (0.6 [95% confidence interval [CI], 0.2-1.0]) compared with K-wires (7.4 [4.8-9.9]) and plating (9.8 [5.3-14.3]). Intramedullary screw fixation also had significantly lower rates of reoperation (4%, [2%-7%]), compared with K-wires (11% [7%-16%]) and plating (11% [0.07-0.17]). Grip strength was significantly higher in IMF (104.4% [97.0-111.8]) compared with K-wires (88.5%, [88.3-88.7]) and plating (90.3%, [85.4-95.2]). Mean odds ratio time was similar between IMF (21.0 minutes [10.4-31.6]) and K-wires (20.8 minutes [14.0-27.6]), but both were shorter compared with plating (52.6 minutes [33.1-72.1]). There were no statistically significant differences in time to radiographic healing, TAM, or rates of reoperation or infection. CONCLUSIONS: This meta-analysis compared the outcomes of metacarpal fixation with IMF, K-wires, or plating. Intramedullary screw fixation provided statistically significant lower DASH scores, higher grip strength, and lower rates of reoperation, suggesting that it is a comparable method of fixation to K-wires and plating for metacarpal fractures.

Romidepsin and Afatinib Abrogate Jak-Signal Transducer and Activator of Transcription Signaling and Elicit Synergistic Antitumor Effects in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphomas are mature lymphoid neoplasias resulting from the malignant transformation of skin-resident T-cells. A distinctive clinical feature of cutaneous T-cell lymphomas is their sensitivity to treatment with histone deacetylase inhibitors. However, responses to histone deacetylase inhibitor therapy are universally transient and noncurative, highlighting the need for effective and durable drug combinations. In this study, we demonstrate that the combination of romidepsin, a selective class I histone deacetylase inhibitor, with afatinib, an EGFR family inhibitor, induces strongly synergistic antitumor effects in cutaneous T-cell lymphoma models in vitro and in vivo through abrogation of Jak-signal transducer and activator of transcription signaling. These results support a previously unrecognized potential role for histone deacetylase inhibitor plus afatinib combination in the treatment of cutaneous T-cell lymphomas.

No Detectable Association Between Virtual Setting for Vasectomy Consultation and Vasectomy Completion Rate.

INTRODUCTION: The COVID-19 pandemic has fueled widespread incorporation of telehealth into urology practices. Vasectomy consultation via telehealth is convenient and improves access to care for male contraception. However, it does not allow for physical examination, inherently leading to possible day-of-procedure cancellations due to unforeseen anatomic concerns. This study aimed to compare vasectomy completion rates between patients undergoing virtual vs in-person consultation. METHODS: All patients seen by a single provider at NYU Langone Health for vasectomy consultation between October 2016 and June 2022 were included in the study. Most patients seen before March 2020 had in-person consultations, whereas the majority of patients seen afterwards had virtual consultations without option for in-person visit due to the emergence of COVID-19. All patients seen virtually were examined in a consult room prior to being prepped for the vasectomy in the procedure room. Visit type, demographic information, and clinical outcomes data were collected for all patients. A chi-square test was used to compare the rate of vasectomy completion between those with in-person and virtual consultation. Analysis was performed using R, version 4.0.5. RESULTS: Four hundred ninety-one patients were seen by a single provider for vasectomy consultation between October 2016 and June 2022. One hundred ninety-seven (40.1%) consultations were performed virtually and 294 (59.9%) consultations were performed in person. Three hundred seventy (75.4%) of all patients seen for consultation (both virtual and in person) ultimately underwent vasectomy. There was no evidence of difference in rate of completing vasectomy after virtual (75.6%) and in-person (75.2%) consultation (P = .91). Two of the 197 (1%) patients who consulted virtually had their vasectomy procedures cancelled on the day of the procedure based on their preoperative exam; one because of abnormal epididymal sensitivity after prior scrotal infection, the other because of a history of orchiopexy that the patient was not aware of until the surgeon started inquiring about scrotal scars present. CONCLUSIONS: Despite the lack of physical examination, virtual vasectomy consultation is both feasible and effective, with rates of vasectomy completion comparable to traditional in-person consultation.

Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma.

Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) comprises heterogeneous lymphoid malignancies characterized by pleomorphic lymphocytes and variable inflammatory cell-rich tumor microenvironment. Genetic drivers in PTCL-NOS include genomic alterations affecting the VAV1 oncogene; however, their specific role and mechanisms in PTCL-NOS remain incompletely understood. Here we show that expression of Vav1-Myo1f, a recurrent PTCL-associated VAV1 fusion, induces oncogenic transformation of CD4+ T cells. Notably, mouse Vav1-Myo1f lymphomas show T helper type 2 features analogous to high-risk GATA3+ human PTCL. Single-cell transcriptome analysis reveals that Vav1-Myo1f alters T cell differentiation and leads to accumulation of tumor-associated macrophages (TAMs) in the tumor microenvironment, a feature linked with aggressiveness in human PTCL. Importantly, therapeutic targeting of TAMs induces strong anti-lymphoma effects, highlighting the lymphoma cells' dependency on the microenvironment. These results demonstrate an oncogenic role for Vav1-Myo1f in the pathogenesis of PTCL, involving deregulation in T cell polarization, and identify the lymphoma-associated macrophage-tumor microenvironment as a therapeutic target in PTCL.

Reduction Techniques in Volar Locking Plate Fixation of Distal Radius Fractures.

Distal radius fractures are the most common upper extremity fracture and volar locking plate fixation has become a common modality for operative management of these injuries over the last 2 decades. However, despite the widespread use of volar locking plates, there remains no comprehensive guide detailing the available reduction techniques using these systems. This review aims to consolidate the reduction techniques from the literature along with the authors' experiences into a blueprint for distal radius fracture reduction when using a volar plate. Techniques described include those with and without use of the plate and with supplementary means of fixation for both extra-articular and intra-articular fracture patterns.

Mentoring and Support for Underrepresented Nursing Faculty: An Integrative Research Review.

BACKGROUND: Nursing faculty members may need several mentors to succeed in scholarly productivity, career development, work-life balance, and socialization in the academy. Underrepresented (UR) faculty report additional challenges to success. PURPOSE: The aim of this study was to search the literature for best practices in mentoring UR faculty. METHODS: An integrative review was conducted to identify best and evidence-based practices for mentoring UR faculty, including gender, sexual minority, race, ethnicity, and geographic remoteness (rural). Fifteen articles were rated on evidence and methodological quality. RESULTS: Successful mentorship programs include honest communication, including all stakeholders in forming a mentoring program, goals and activities that come from the mentees, and guaranteed resources. CONCLUSIONS: Underrepresented nursing faculty may benefit from formal mentoring programs, but more research is needed.

Motivators of Continued Participation in Public Health Emergency Response Among Federal Public Health Workers: A Qualitative Study.

The purpose of this study was to identify factors that motivate public health workers to deploy to the field during an emergency event. We conducted 25 semistructured interviews with employees at the US Centers for Disease Control and Prevention, all of whom had deployed to the field for the 2014-2016 Ebola, 2016-2017 Zika, and 2017 hurricane responses. We used a grounded theory approach in our analysis of the data. Themes that emerged from the interviews related to responder autonomy, competence, and relatedness, which are consistent with self-determination theory. Motivating factors included having clarity about the response role, desire to be challenged, ability to apply existing skills in the field (or apply new skills learned during deployment to their home office), desire to be helpful, and feeling rewarded by working with affected populations, communities, and other response staff. These preliminary findings suggest that introjected and identified motivating factors may form the foundation of willingness among public health workers to assist during an emergency event. Understanding what motivates staff at public health agencies to participate in emergency deployment can inform the development of recruitment strategies, strengthen effectiveness of response activities, and improve overall agency preparedness.

Are Infertile Men Less Healthy Than Fertile Men? An Analysis of the National Survey for Family Growth.

OBJECTIVE: To characterize the general health status of infertile men in the United States using a nationally representative sample of men. METHODS: Using the National Survey for Family Growth from 2011 to 2017, infertile subgroups were created using a range of inclusion criteria. Univariate and multivariate analyses were conducted comparing these men to fertile men. RESULTS: Using population estimates, 6.5 million men with reduced fertility potential were compared to 26 million fertile men. After controlling for demographic and healthcare utilization factors, these groups did not have significantly different rates of key medical co-morbidities, including cancer, obesity, and overall disability. Looking at the subset of men who had received a specific infertility diagnosis, estimated as a population of nearly 600,000 men, this pattern held, in that there were no significant differences in the rates of medical co-morbidities. Notably, the rate of male infertility evaluation among potentially infertile men was only 50%. These findings also persisted after a propensity-matched analysis. CONCLUSION: In this cohort, there was no significant relationship between infertility and specific medical co-morbidities. We must consider the influence of sample selection as we continue to investigate the relationship between medical co-morbidities and reduced fertility potential. Given the persistent low rates of infertility evaluation, even among men who seek medical advice to conceive, we must continue to search for ways to characterize the infertile male population while simultaneously working to improve access.

Jak-STAT Inhibition Mediates Romidepsin and Mechlorethamine Synergism in Cutaneous T-Cell Lymphoma.

Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. In this study, we show synergistic antilymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in cutaneous T-cell lymphoma cell lines and primary samples with strong antitumor effects in an in vivo model of Sézary syndrome. Mechanistically, gene expression profiling points to abrogation of Jak/signal transducer and activator of transcription (STAT) signaling as an important mediator of this interaction. Consistently, the combination of mechlorethamine plus romidepsin resulted in downregulation of STAT5 phosphorylation in romidepsin-sensitive cell lines and primary Sézary syndrome samples, but not in romidepsin-resistant tumors. Moreover, in further support of Jak/STAT signaling as a modulator of romidepsin activity in cutaneous T-cell lymphoma, treatment with romidepsin in combination with Jak inhibitors resulted in markedly increased therapeutic responses. Overall, these results support a role for romidepsin plus mechlorethamine in combination in the treatment of cutaneous T-cell lymphoma and uncover a previously unrecognized role for Jak/STAT signaling in the response to romidepsin and romidepsin-based combination therapies in Sézary syndrome.

How do we counsel men with obstructive azoospermia due to CF mutations?-a review of treatment options and outcomes.

Obstructive azoospermia (OA) is a rare cause of male infertility, with Congenital Bilateral Absence of The Vas Deferens (CBAVD) being a major cause. A wealth of literature has established an irrefutable link between CFTR mutations and CBAVD, with CBAVD affecting almost all men with cystic fibrosis (CF) disease and a significant portion of men that are CFTR mutation carriers. In the past two decades, assisted reproductive technologies have made the prospect of fathering children a viable possibility in this subset of men, using a combination of sperm extraction techniques and intracystoplasmic sperm injection (ICSI). In order to assess techniques for sperm retrieval, as well as reproductive outcomes, a systemic search of the MEDLINE database was conducted for all articles pertaining to management options for CBAVD, and also all reports describing outcomes of these procedures in the CBAVD population. Both epididymal and testicular sperm extraction (TESE) are viable options for men with CBAVD, and though rigorous data are lacking, live birth rates range from 8% to 50% in most small retrospective series and subset analyses. In addition, there does not appear to be significant differences in the rate of live birth or complications and miscarriages between the various techniques, though further investigation into other factors that limit reproductive potential of men with CFTR mutations and CBAVD is warranted.

Evaluating the unevaluated: a secondary analysis of the National Survey for Family Growth (NSFG) examining infertile women who did not access care.

PURPOSE: To characterize the demographic differences between infertile/sub-fertile women who utilized infertility services vs. those that do not. METHODS: A retrospective analysis of cross-sectional data obtained during the 2011-2013, 2013-2015, and 2015-2017 cycles of National Survey for Family Growth from interviews administered in home for randomly selected participants by a National Center of Health Statistics (NCHS) surveyor was used to analyze married, divorced, or women with long-term partners who reported difficulty having biological children (sub-fertile/infertile women). Demographic differences such as formal marital status, education, race, and religion were compared between women who presented for infertility care vs. those that did not. The primary outcome measure was presenting for infertility evaluation and subsequently utilizing infertility services. Healthcare utilization trends such as having a usual place of care and insurance status were also included as exposures of interest in the analysis. RESULTS: Of the 12,456 women included in the analysis 1770 (15.3%) had used infertility services and 1011 (8.3%) said it would be difficult for them to have a child but had not accessed infertility services. On univariate analysis, compared to women who used infertility services, untreated women had lower average household incomes (295.3 vs. 229.8% of the federal poverty line respectively). Untreated women also had lower levels of education and were more likely to be divorced or never have married. In terms of health status, unevaluated women were less likely to have a usual place for healthcare (87.3%) as compared to women presenting for fertility care (91.9%) (p = 0.004). When examining insurance status, 23.3% of unevaluated women were uninsured as compared to 8.3% of evaluated women. On multivariate analysis, infertile women without insurance were at 0.37 odds of utilizing infertility care compared to women with insurance. CONCLUSIONS: Demographic factors are associated with the utilization of infertility care. Insurance status is a significant predictor of whether or not infertile women will access treatment. Data from the three most recent NSFG surveys along with prior analyses demonstrate the need for expanded insurance coverage in order to address the socioeconomic disparities between infertile women who are accessing services vs. those that are not.

Vasectomy in Men without Children: Demographics and Family Planning Attitudes from the National Survey for Family Growth.

INTRODUCTION: To investigate the ethically challenging scenario of a childless man requesting a vasectomy, we compared vasectomy reversal rates and family planning attitudes in men who underwent vasectomy with and without fathering a child. METHODS: We performed an analysis of the 2002 to 2006, 2006 to 2010, 2011 to 2013, 2013 to 2015 and 2015 to 2017 waves of the National Survey for Family Growth, a nationally representative survey of family planning in the United States. We compared demographic information and family planning attitudes among men who had undergone vasectomy with and without having children. RESULTS: Of the 29,192 men surveyed 1,043 (3.6%) reported undergoing a vasectomy. Of the men reporting vasectomy, 4.4% (95% CI 3.2-6.0) underwent the procedure without having had children. Compared to men with children, men without children were less likely to have ever been married and were more likely to not identify with any religion. Whereas 1.2% (95% CI 0.5-2.4) of men with children underwent vasectomy reversal during the followup, 0% of men without children underwent reversal. CONCLUSIONS: Men who undergo vasectomy without having children constitute a small but distinct population of men. During 7-year followup after vasectomy, men who have not fathered children do not express higher rates of postvasectomy regret.