Addressing cervical cancer disparities in Texas: Expansion of a community-based prevention initiative for medically underserved populations.

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services.

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

PURPOSE: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats. METHODS: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed. RESULTS: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone. CONCLUSIONS: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

Interprofessional geriatric and palliative care intervention associated with fewer hospital days.

BACKGROUND: With increasing complexity of our aging inpatient population, we implemented an interprofessional geriatric and palliative care intervention on a hospitalist service. This study aimed to measure the intervention's impact on length of stay (LOS), 30-day readmission, and the daily intensity of inpatient services utilization. METHODS: Using a nonrandomized controlled intervention at a 1000-bed U.S. academic quaternary medical center, we studied 13,941 individuals admitted to a general medicine hospitalist service (of which 5644 were age > =65 years); 1483 were on intervention teams (576 age > =65 years), 5413 concurrent controls, and 7045 historical controls. On 2 of 11 hospitalist teams, a geriatrician, palliative care physician and social worker attended multidisciplinary discharge rounds twice weekly, to recommend inpatient geriatric or palliative care consult (GPCC), postacute nursing or home care, versus postdischarge outpatient consultation. We measured the difference in improvement over time between intervention and control team patients for the following: (1) LOS adjusted for case-mix index, (2) 30-day readmissions, and (3) intensity of hospital service utilization (mean services provided per patient per day). RESULTS: Adjusted LOS (in hospital days) was decreased by 0.36 days (p = 0.039) for the 1483 patients in the intervention teams, with greater LOS reduction of 0.55 days per admission (p = 0.022) on average among the subset of 576 older patient admissions. Readmissions were unchanged (-1.17%, p = 0.48 for all patients; 1.91%, p = 0.46 for older patients). However, the daily relative value unit (RVU) utilization was modestly increased for both the overall and older subgroup, 0.35 RVUs (p = 0.041) and 0.74 RVUs (p < 0.001) per patient-day on average across the intervention teams, respectively. CONCLUSION: An interprofessional intervention of geriatric and palliative care consultation in collaboration with a hospitalist service may reduce LOS, especially for geriatric patients, without an increase in readmissions. This model may have broader implications for hospital care and should be further studied.

Predicting the disaster - The role of CRP in acetabular surgery.

OBJECTIVES: Acetabular fractures represent a complex surgical challenge. Given the heterogenous fracture pattern, the patient characteristics and spectrum of complications demand individual solutions. Surgical site infections (SSI) threaten osteosynthesis, and early detection of them and treatment remain crucial. What is the value of postoperative C-reactive protein (CRP) in this group of patients as well as its normal course? DESIGN & METHODS: 115 patients with isolated fractures of the acetabulum were retrospectively evaluated. CRP, white blood cell count (WBC) and fracture patterns as well as patient characteristics were assessed for 20 days following operative fixation of the acetabular fracture (n = 71) and in fractures that were managed conservatively (n = 44). RESULTS: Twelve patients suffered an infectious complication. With a one-phase decay, 70.55% of the variance of postoperative CRP kinetics was predicted. To anticipate maximum CRP as well as an infection, the preoperative CRP represented the best prognostic parameter. To predict an infection, the single variable "peak CRP value above 100 mg/l" resulted in a sensitivity and specificity of 91.67% and 36.21%, respectively. Combining a second peak of CRP with maximum CRP and day 5 CRP value for receiver-operating characteristic (ROC) analysis resulted in 83.3% and 88.1%, respectively. CONCLUSIONS: Predicting surgical site infections after an acetabular fracture is most predictive when analyzing the maximum overall CRP, the second peak and the CRP after day 5. With a combination of these parameters, a sensitivity and specificity of 83.3% and 88.1% to detect an infection was achieved.

C-reactive protein in spinal surgery: more predictive than prehistoric.

PURPOSE: In spinal surgery, surgical site infections (SSI) after dorsal spondylodesis lead to severe short- and long-term complications. Despite various clinical and serological evidence, the detection of a postoperative SSI remains crucial. In this retrospective cohort study, we determined the prognostic value of C-reactive protein (CRP) kinetics after open reduction and dorsal spondylodesis in the development of a SSI. METHODS: We retrospectively analyzed 192 patients from 2016 to 2018 undergoing open reduction and dorsal spondylodesis with and without SSI for 20 days at a level-I trauma center and assessed their serological and clinical characteristics. RESULTS: On day 7 and 8 after surgery, patients who developed a SSI displayed significantly higher CRP levels. A second peak after the initial maximum of CRP and a restricted failure to decline as well as a maximum CRP of more than 225 mg/l predict an infectious complication with a sensitivity of 92.9%, and a specificity of 78.2%. A binary logistic regression leads to 85.7% and 69.7%, respectively. A one-phase decay exponential regression can predict 75.6% of the variance after the initial peak of CRP. CONCLUSION: Our study demonstrates a high value of postoperative CRP kinetics in SSI detection after dorsal spondylodesis. Moreover, we observed typical CRP levels with a specific course as indicative predictors that may facilitate an early SSI detection in clinical practice.

Vulvar intravascular papillary endothelial hyperplasia or Masson's tumor: A case report.

Masson's tumor, also known as intravascular papillary endothelial hyperplasia (IPEH), is a rare and benign vascular disease in which there is a reactive hyperplasia of intravascular endothelial cells. This tumor is most commonly found in soft tissues in the head, neck and upper extremities. We report a rare case of IPEH on the vulva. A Hispanic woman in her mid-thirties presented with a painful and pruritic left vulvar mass. On physical examination, a pedunculated mass was visualized on the left labia majora. Under pathologic examination, it was concluded the lesion was IPEH and it was surgically excised. This is a rare case of IPEH located on the vulva. However, despite this rarity, a simple local excision could be used to manage IPEH.

Comparing Methadone Rotation to Consensus Opinion.

CONTEXT: Methadone is a complex but useful medication for pain management in palliative care. Recent expert opinions have been published on the safe and effective use of methadone. OBJECTIVES: To determine the success of methadone rotations and evaluate concordance with consensus recommendations by a palliative care consult service. METHODS: A retrospective study of methadone rotation practice by a palliative care consult service and outcomes for patients hospitalized between January 1, 2012 and December 31, 2018 at a single academic medical center. A successful rotation was defined as a 30% reduction in pain or as-needed medication use sustained for at least three consecutive days. Patient outcomes were compared with expert consensus recommendations. RESULTS: About 59 patients met the inclusion criteria. The study population was mostly Caucasian men and women of equal proportions who were started on methadone for inadequate pain control. Sixty-eight percent of patients were successfully rotated. Subjects who were rotated using a standardized protocol were six times more likely to have a successful rotation (odds ratio 6.28 [1.25-30.92]; P = 0.0238). CONCLUSION: The utilization of a standardized protocol was associated with better patient outcomes.

Inflammation-induced glycolytic switch controls suppressivity of mesenchymal stem cells via STAT1 glycosylation.

Mesenchymal stem cells (MSCs) represent key contributors to tissue homeostasis and promising therapeutics for hyperinflammatory conditions including graft-versus-host disease. Their immunomodulatory effects are controlled by microenvironmental signals. The MSCs' functional response towards inflammatory cues is known as MSC-"licensing" and includes indoleamine 2,3-dioxygenase (IDO) upregulation. MSCs use tryptophan-depleting IDO to suppress T-cells. Increasing evidence suggests that several functions are (co-)determined by the cells' metabolic commitment. MSCs are capable of both, high levels of glycolysis and of oxidative phosphorylation. Although several studies have addressed alterations of the immune regulatory phenotype elicited by inflammatory priming metabolic mechanisms controlling this process remain unknown. We demonstrate that inflammatory MSC-licensing causes metabolic shifts including enhanced glycolysis and increased fatty acid oxidation. Yet, only interfering with glycolysis impacts IDO upregulation and impedes T-cell-suppressivity. We identified the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 pathway as a regulator of both glycolysis and IDO, and show that enhanced glucose turnover is linked to abundant STAT1 glycosylation. Inhibiting the responsible O-acetylglucosamine (O-GlcNAc) transferase abolishes STAT1 activity together with IDO upregulation. Our data suggest that STAT1-O-GlcNAcylation increases its stability towards degradation thus sustaining downstream effects. This pathway could represent a target for interventions aiming to enhance the MSCs' immunoregulatory potency.

Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis.

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

[Surgical treatment of bites]. / Chirurgische Behandlung von Bissverletzungen.

OBJECTIVE: Thorough and profound debridement for acute bite injuries while sparing nerves, vessels and tendons. INDICATIONS: Acute traumatic and late presented bite injuries. CONTRAINDICATIONS: General contraindication for anesthesia or surgery. SURGICAL TECHNIQUE: Extensive flabellate local anesthesia/general anesthesia, wound irrigation using 0.9% NaCl or antiseptic solutions, removal of avital tissues, wound debridement, wound edge excision, anew extensive irrigation, drainage if necessary, wound closure where applicable (except older or punctual deep injuries), bandage, elastic wrapping and immobilization. If necessary, plastic surgery with coverage of remaining defects. POSTOPERATIVE MANAGEMENT: Immobilization with initially daily wound evaluation, removal of drainage/loop on postoperative day 2; if necessary, antibiotic therapy with amoxicillin and clavulanic acid in high-risk wounds (e.g., puncture wounds, joint or bone involvement, extensive soft tissue squeezing), suture removal on day 10-12 after surgery. RESULTS: Of 142 bite injuries that were treated and retrospectively evaluated, 46% were caused by dogs and 32% by cats. Patients were on average 44 years old; 55% of all dog bites affected women, but 67% of all cat bites. In 48% of the cases, general anesthesia was necessary. The postoperative infection rate was 6.3%.

Interprofessional Rounds Improve Timing of Appropriate Palliative Care Consultation on a Hospitalist Service.

Despite known benefits, palliative care (PC) consultation for hospitalized patients remains underutilized. The objective was to improve frequency and timeliness of appropriate inpatient PC consultation. On 2 of 11 hospitalist teams, a PC representative attended discharge rounds twice a week. Control teams' discharge rounds were unenhanced. Subjects were all patients admitted to a hospitalist service in a quaternary academic medical center. The primary outcome was change in provision of PC consultation over time; the secondary outcome was change in time-to-consult (days). Hospitalists were surveyed regarding the intervention. The unadjusted proportion of patients receiving PC consultation increased from 2.7% to 5.2% on the intervention teams. Compared to control teams over time and adjusting for multiple covariates, the intervention increased PC consultation (difference-in-difference [DID] = 1.0 percentage-point increase [95% CI = 0.3%-1.8%]) and decreased time to consult (DID = -5 days [95% CI = -11 to -1]) in patients admitted for noncancer diagnoses. Hospitalists thought the intervention facilitated effective patient care without increased burden.

Single-Center Experience Providing Palliative Care to Pediatric Patients with End-Stage Renal Disease.

BACKGROUND: End-stage renal disease (ESRD) affects nearly 1400 new children each year in the United States. Morbidity and mortality rates remain high for pediatric patients with ESRD, including those that have received a renal transplant. OBJECTIVE: To better understand ESRD patients referred to palliative care, including their physical symptoms, topics discussed, and themes emerging during initial palliative care consultation. DESIGN/SUBJECTS: This study is a retrospective chart review of pediatric ESRD patients who received a palliative care consult. Physical symptoms, core topics, and themes were identified by the interprofessional study team. RESULTS: The study team found 35 patients met inclusion criteria during the study period. The most common standard palliative care metric noted was "complex or time-intensive communication and interdisciplinary social support." Pain was the most common physical symptom addressed with goals of care and communication the most common topics discussed. Themes emerging described the emotional distress of patients and parents as well as prognostic discussions. CONCLUSIONS: This study demonstrates one institution's experience with pediatric ESRD patients undergoing consultation with the pediatric palliative care service. More research is necessary in this population to better describe the best focus for palliative care teams.

[Treatment of traumatic lesions of the bursa olecrani and chronic bursitis olecrani]. / Behandlung der traumatisch eröffneten Bursa olecrani und der chronischen Bursitis olecrani.

OBJECTIVE: Complete olecranon bursectomy with debridement, protection of veins and nerves. Risk-adapted antibiotic therapy and early functional aftercare. INDICATIONS: Acute, traumatic laceration of the bursa olecrani, chronic therapy-resistant bursitis olecrani. CONTRAINDICATIONS: For traumatic bursa injuries: general contraindications for anesthesia and surgery; chronic bursitis: initially not closable skin defect (plastic surgery required), hemodynamically instable patient (e.g. systemic inflammatory response syndrome [SIRS] or sepsis), pre-existing skin infection. SURGICAL TECHNIQUE: Local anesthesia beyond the lesion, careful debridement, identification and removal of the entire bursa, excision of contaminated skin, lavage, drain insertion (Redon, Easy-flow, Penrose). Wound closure, elastic bandage, and splint. POSTOPERATIVE MANAGEMENT: Elastic bandage for 2 days, followed by drain removal. Wound assessment, early functional aftercare without splint, antibiotic therapy in septic bursitis for 2 weeks, PRICE scheme. Removal of stitches after 10-12 days. RESULTS: Over 5 years, 138 cases of traumatic bursa lesion or chronic bursitis olecrani were treated in our clinic, 82 patients underwent surgery. Ten patients were treated with vacuum-assisted closure therapy and consecutive wound healing; fistulae occurred in two patients and in another two dehiscence developed. All of the defects could be closed without flaps.

The PD-1/PD-L1 axis contributes to immune metabolic dysfunctions of monocytes in chronic lymphocytic leukemia.

Immune dysfunctions in chronic lymphocytic leukemia (CLL) contribute to tumor immune escape and attenuate immune-based therapies. Monocytes/macrophages represent key components of cancer immune surveillance and effectors for antibody-mediated antitumor effects. Monocytes display an altered subset composition in CLL. Moreover, we find a changed metabolic phenotype: glucose uptake, glucose transporters and expression of glycolytic molecules are reduced. Our data establish a link between glycolytic competence and monocyte-mediated phagocytosis of tumor cells. Furthermore, we report that CLL monocytes express Bruton's tyrosine kinase (BTK). Our observations suggest that using BTK inhibitors in CLL might further aggravate the observed immune metabolic defects in monocytes. Triggering the programmed cell death-1 (PD-1) checkpoint on monocytes hampers glycolysis, phagocytosis and BTK signaling. Conversely, disrupting PD-1/PD-L1 signaling reverses these immune metabolic dysfunctions. Taken together, our findings imply a novel metabolic interplay between CLL cells and monocytes and that blocking PD-1/PD-L1 might restore metabolic together with antitumor activity of CLL monocytes/macrophages.

[Surgical treatment of a complex adolescent carpal fracture : A rare injury to the growing skeleton]. / Versorgung einer komplexen jugendlichen Handwurzelfraktur : Eine seltene Verletzung am wachsenden Skelett.

We report the case of a 15-year-old boy with combined fractures of the scaphoid, capitate, and hamate that represents a rare variation of the well-known Fenton's syndrome. Fixation was performed for the unstable fractures of the scaphoid and capitate with the use of cannulated Herbert screws and K­wires respectively. K­wires were removed after 6 months, with subsequent physiotherapy. After 6 months, CT confirmed complete consolidation of the two surgically treated carpal fractures and the conservatively treated fracture of the hamate. Regarding function, the patient is able to incorporate the hand into his school-related activities and has a good range of motion, with strong closure of the fist.

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

BACKGROUND: Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. PROCEDURE: This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. RESULTS: Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CONCLUSIONS: CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children.

Use of intravenous acetaminophen (paracetamol) in a pediatric patient at the end of life: case report.

BACKGROUND: For the better part of 100 years, acetaminophen (or paracetamol as it is known outside of the United States) has been a common first-line analgesic in pediatrics and is typically well tolerated with minimal side effects. Its use as an anti-pyretic is also well-documented and thus it is used broadly for symptom control in the general pediatric population. DISCUSSION: In pediatric palliative care, acetaminophen is also used as an adjuvant to opioid therapy for pain as well as an anti-pyretic. For many pediatric patients near end-of-life, however, the ability to tolerate oral intake is diminished and rectal suppository administration can be distressing or contraindicated as in the setting of neutropenia, thus limiting use of acetaminophen by its usual routes. In Europe and Australia, an intravenous formulation of acetaminophen has been used for many years and has only recently become available in the United States. CONCLUSION: Here, we describe a case using intravenous acetaminophen in a pediatric patient at the end of life.

A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage leukemic cells.

CD19 is a B-lineage-specific transmembrane signaling protein participating in the control of proliferation and differentiation. It is present at high surface density on chronic B-lymphocytic leukemia (B-CLL) cells and cells of other B-cell malignancies, and is a prime target for therapy with antibody-derived agents. Many attempts have been made to target malignant cells via CD19, but to date none of these agents have received drug approval. Here we report the design of a monovalent immunotoxin consisting of a CD19-specific single-chain Fv antibody fragment fused to a derivative of Pseudomonas Exotoxin A. This fusion protein induced efficient antigen-restricted apoptosis of several human leukemia- and lymphoma-derived cell lines including Nalm-6, which it eliminated at an effective concentration (EC(50)) of 2.5 nM. The agent displayed synergistic toxicity when used in combination with valproic acid and cyclosporin A in cell-culture assays. It induced apoptosis of primary malignant cells in 12/12 samples from B-CLL patients, including patients responding poorly to fludarabine, and of cells from one pediatric acute lymphoblastic leukemia patient. In NOD/SCID mice transplanted with Nalm-6 cells, the toxin prevented engraftment and significantly prolonged survival of treated mice. Owing to its efficient antigen-restricted antileukemic activity, the agent deserves further development towards clinical testing.

Prostate cancer mortality in Connecticut, Iowa and New Mexico African American men.

We sought to assess trends in prostate cancer incidence, treatment and mortality in African American men by means of analysis of prostate cancer data from three states, Connecticut, Iowa and New Mexico, all participants in the Surveillance, Epidemiology, and End Results (SEER) Program. Compared with levels before prostate specific antigen (PSA) testing, prostate cancer incidence increased in all three states after widespread testing. For men diagnosed with localized or regional prostate cancer, the respective increases in radical prostatectomy in Connecticut, Iowa, and New Mexico were 3.2, 2.3, and 4.9 times pre-test levels. Age-standardized mortality in Connecticut and Iowa increased slightly; in New Mexico the 104.7 deaths per 100,000 in 1979-1986, 62.1 in 1987-1990, dropped to 47.6 in 1991-1998, an amount of decline that was statistically significant. Introduction of PSA testing influenced early detection and treatment of prostate cancer in all three states. Although decline in prostate cancer mortality in New Mexico over time may be linked with use of the PSA test and definitive therapy, the relationship among these factors, and thus the proper treatment for the early stages of this condition, is unclear on the basis of these data.