Ablation, Osteoplasty, Reinforcement, and Internal Fixation as a New Alternative First-Line Management for Osteolytic Pelvic Metastases.

Many orthopaedic procedures for osteolytic metastases are performed using surgical techniques and implants that are used in arthroplasties or trauma surgeries. There is a need for development of skeletal metastasis-specific procedures. Massive osteolytic metastases in periacetabular regions are managed with open surgical procedures when radiation and antiresorptive agents fail to prevent development and progression of the lesion. An ideal procedure for osteolytic metastases would decrease cancer burden and stabilize weakened bones for continued ambulatory oncologic care without delay. Therefore, ablation, osteoplasty, reinforcement, and internal fixation (AORIF) is a new alternative percutaneous procedure for osteolytic metastases in pelvis and other periarticular osteolytic metastases. Percutaneously inserted cannulated screws provide a universal portal for catheters for ablation, balloon osteoplasty, and zoledronate-loaded bone cement. AORIF reduces local cancer burden by radiofrequency ablation and improves bone strength immediately with polymethyl methacrylate bone cement for enhanced ambulatory oncologic care. Similar to other reported series of percutaneous reinforcement procedures, AORIF improves ambulatory status for localized bone defects in patients who seek anticancer drug therapies. AORIF does not provide anatomic restoration of established comminuted acetabular fractures or protrusio acetabuli but improves pain and ambulatory status for continued oncologic care. AORIF is a new alternative first-line minimally-invasive procedure for patients with advanced cancers and osteolytic pelvic metastases.

Ablation, Osteoplasty, Reinforcement, and Internal Fixation for Percutaneous Endoskeletal Reconstruction of Periacetabular and Other Periarticular Osteolytic Metastases.

For osteolytic metastatic disease in the pelvis and acetabulum of patients with unpredictable and limited lifespans, first-line treatment focuses on targeting the primary cancer with anticancer drugs, osteoclastogenesis inhibitors, analgesics, and radiation therapy. Uncontrolled pain and progressive bone destruction refractory to these interventions often warrant surgical stabilization. Conventional open surgical procedures using metal implants or prostheses may provide immediate biomechanical stability but are associated with various complications without local cancer control. Outcomes of conventional open surgical reconstructive procedures depend on local cancer progression and progressive bone loss. Percutaneous cancer ablation and bone augmentation with polymethyl methacrylate cement alone often lack optimal internal fixation and integration with surrounding bone. The current literature demands a multipurpose minimally invasive surgical intervention that provides local cancer control, bone protection, and stabilization. An overview of new, alternative percutaneous procedure consisting of image-guided ablation, balloon osteoplasty, cement reinforcement, and internal fixation, which offers a minimally invasive percutaneous treatment option for patients with osteolytic metastatic cancers with the advantages of concurrent thermal necrotization of cancers, zoledronate-loaded bone cementoplasty, and surgical stabilization in an ambulatory surgery setting, is warranted. Early clinical results have shown that the ablation, balloon osteoplasty, cement reinforcement, and internal fixation is a safe and effective alternative solution for stabilizing and palliating osteolytic lesions in patients seeking new effective therapies in the era of rapidly evolving oncologic care.

Femoral and Tibial Reconstruction for Skeletal Metastases and Pathologic Fractures.

Skeletal metastases of the femur and tibia leading to pathologic fractures or large skeletal defects can be managed with surgical reconstruction, resulting in improved patient outcomes and functionality. The indications for femoral and tibial reconstruction are dependent on several factors, including goals of management, age, comorbidities, site and extent of the lesion, soft-tissue involvement, and history of radiation or other systemic therapy. The goal of reconstruction of large bone defects is to restore anatomy and function while minimizing the risk of complications, implant failure, and subsequent revision procedure. Common reconstructive options include fixation with plates and screws, intramedullary nails, and endoprosthesis implantation.

A randomized, phase II, three-arm study of two schedules of ixabepilone or paclitaxel plus bevacizumab as first-line therapy for metastatic breast cancer.

The aim of this phase II trial was to estimate the objective response rate (ORR) of two different schedules of ixabepilone [weekly or every 3 weeks (Q3W)] combined with bevacizumab, relative to a reference arm of weekly paclitaxel and bevacizumab. Patients with human epidermal growth factor receptor 2-normal, chemotherapy-naïve metastatic breast cancer (MBC) were randomized 3:3:2 to ixabepilone 16 mg/m(2) weekly plus bevacizumab 10 mg/kg Q2W (Arm A: n = 46); ixabepilone 40 mg/m(2) Q3W (reduced to 32 mg/m(2) after four cycles of treatment) plus bevacizumab 15 mg/kg Q3W (Arm B: n = 45); or paclitaxel 90 mg/m(2) weekly plus bevacizumab 10 mg/kg intravenous infusion Q2W (Arm C: n = 32). Of 123 randomized patients, 122 were treated. All were followed for ≥19 months; 5 % of patients remained on study treatment at the time of this analysis. Grade 3 or 4 neutropenia was more common in Arm B (60 %) than Arms A (16 %) or C (22 %); other adverse events were similar. The investigator-assessed ORR was 48, 71, and 63 % for Arms A, B, and C, respectively. Median progression-free survival (randomized patients) was 9.6 months in Arm A, 11.9 months in Arm B, and 13.5 months in Arm C. In conclusion, ixabepilone Q3W plus bevacizumab has clinical activity as first-line therapy for MBC relative to paclitaxel plus bevacizumab, but with significantly greater risk of grade 3 or 4 neutropenia. In addition, these data suggest that weekly dosing of ixabepilone may be less active than Q3W dosing, but with less neutropenia.

Emerging Minimally Invasive Percutaneous Procedures for Periacetabular Osteolytic Metastases.

➤: Periacetabular osteolytic skeletal metastases are frequently associated with pain and impaired ambulatory function. Minimally invasive techniques allow for the restoration of ambulation without interrupting critical systemic cancer therapy. ➤: The open surgical management of massive periacetabular osteolytic lesions, such as by curettage, internal fixation, or complex total hip reconstruction, is associated with blood loss, hospitalization, rehabilitation, and complications such as infection or delayed wound-healing. ➤: Minimally invasive percutaneous procedures have become increasingly popular for the management of periacetabular osteolytic metastases by interventional oncologists and orthopaedic surgeons before complex open surgical procedures are considered. ➤: Minimally invasive procedures may include various methods of cancer ablation and reinforcement techniques. Minimally invasive procedures may entail cancer ablation, polymethylmethacrylate (PMMA) cement reinforcement, balloon osteoplasty, percutaneous screw fixation, or combinations of the aforementioned techniques (e.g., ablation-osteoplasty-reinforcement-internal fixation [AORIF]).

Stimulant use interventions may strengthen 'Getting to Zero' HIV elimination initiatives in Illinois: Insights from a modeling study.

OBJECTIVE(S): Getting to Zero (GTZ) is an Illinois-based HIV elimination initiative. GTZ identifies younger Black men who have sex with men (YBMSM) as a population who have experienced disproportionate HIV incidence. Rising stimulant use among YBMSM has been determined to impede engagement in the HIV prevention and treatment continua for reducing onward HIV transmission. Given the limited development of dedicated or culturally appropriate interventions for this population, this modeling study explores the impact of stimulant use on HIV incidence among YBMSM and assesses the impact of interventions to treat stimulant use on downstream HIV transmission to achieve GTZ goals. METHODS: A previously developed agent-based network model (ABNM), calibrated using data for YBMSM in Illinois, was extended to incorporate the impact of stimulant use (methamphetamines, crack/cocaine, and ecstasy) on sexual networks and engagement in HIV treatment and prevention continua. The model simulated the impact of a residential behavioral intervention (BI) for reducing stimulant use and an outpatient biomedical intervention (mirtazapine) for treating methamphetamine use. The downstream impact of these interventions on population-level HIV incidence was the primary intervention outcome. RESULTS: Baseline simulated annual HIV incidence in the ABNM was 6.93 [95% Uncertainty Interval (UI): 6.83,7.04] per 100 person years (py) and 453 [95% UI: 445.9,461.2] new infections annually. A residential rehabilitation intervention targeted to 25% of stimulant using persons yielded a 27.1% reduction in the annual number of new infections. Initiating about 50% of methamphetamine using persons on mirtazapine reduced the overall HIV incidence among YBMSM by about 11.2%. A 30% increase in antiretroviral treatment (ART) and preexposure prophylaxis (PrEP) uptake in the non-stimulant using YBMSM population combined with a 25% uptake of BI for stimulant using persons produces an HIV incidence consistent with HIV elimination targets (about 200 infections/year) identified in the GTZ initiative. CONCLUSIONS: Behavioral and biomedical interventions to treat stimulant use, in addition to expanding overall ART and PrEP uptake, are likely to enhance progress towards achieving GTZ goals.

The relationship between posttraumatic and depressive symptoms during virtual reality exposure therapy with a cognitive enhancer.

Two studies suggest that reductions in posttraumatic symptoms (Aderka et al., 2013) and cognitions (Zalta et al., 2014) precede reductions in depressive symptoms during prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD) in female assault survivors. The present study explored the temporal relationship between posttraumatic and depressive symptoms in a randomized trial of D-Cycloserine (DCS) versus placebo augmented virtual reality exposure (VRE) therapy for chronic World Trade Center-related PTSD following the September 11, 2001 terrorist attacks. Twenty-five male and female participants were randomly assigned to receive either 100 mg DCS (N = 13) or placebo (N = 12) 90 min before 12 weekly VRE sessions. Participants contributed a total of 280 weekly PTSD Checklist (PCL; Weathers et al., 1993) and Beck Depression Inventory-second edition (BDI-II; Beck et al., 1996) symptom scores. Two sets of mediation analyses for longitudinal mixed models assessed the effects of 1) lagged PCL on BDI-II (Model 1), and 2) lagged BDI-II on PCL (Model 2) in the VRE-DCS and VRE-Placebo treatment groups, respectively. Results revealed reciprocal relations between posttraumatic and depressive symptoms during VRE treatment, although reductions in posttraumatic symptoms led to subsequent reductions in depressive symptoms to a greater extent than the converse. These effects were stronger in the DCS-enhanced group. Findings suggest that VRE primarily decreases posttraumatic symptoms, which in turn leads to decreased depressive symptoms, and that DCS may strengthen these effects.

Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).

Mother-to-child transmission of HIV-1: timing and implications for prevention.

This article provides a synthesis of clinical trial data with an aim to deduce the timing of mother-to-child transmission of HIV-1. Because transmission of the infection to the infant through breastfeeding is one of the main challenges in fighting paediatric HIV/AIDS in the developing world, we present separate estimates for the timing of HIV transmission for non-breastfeeding and breastfeeding populations. Our estimates predict that, for non-breastfeeding populations, 50% of HIV infections are transmitted to the infant at the very end of pregnancy, near to the time of labour. For breastfeeding populations, the postnatal period accounts for most of the HIV infections transmitted to the infant. We discuss the potential benefit of exclusive breastfeeding for the first 6 months of life as a policy to decrease the magnitude of HIV transmission. Furthermore, we present the hypothesis, based on recent research findings of viral latency, that the time when a fetus initially encounters the virus might not be when infection is established. We discuss the implications of this hypothesis and how it could lead to new interventions for the prevention of mother-to-child HIV transmission.

Prospective randomized trial of pre-emptive analgesics following ambulatory inguinal hernia repair: intravenous ketorolac versus diclofenac suppository.

BACKGROUND: A pre-emptive non-steroidal anti-inflammatory drug is routinely given to patients undergoing ambulatory inguinal hernia repair. The present prospective randomized trial was undertaken to compare the efficacy of intravenous ketorolac and rectal diclofenac for ambulatory inguinal hernia repairs. METHODS: Between June 1999 and February 2001, a total of 108 patients who underwent ambulatory inguinal hernia repairs under general anaesthesia were recruited. Patients were randomized to receive either intravenous ketorolac 30 mg immediately prior to induction of general anaesthesia (n = 54) or rectal diclofenac 50 mg after signing consent at the Day Surgery Centre (n = 54). RESULTS: The demographic features, hernia types, anaesthetic time, dosage of anaesthetic medication and operative details of the two groups were comparable. There was no significant difference in total amount of analgesic consumption and linear analogue pain scores after operation. With regard to recovery variables, the respective times taken to regain ambulation and micturition were similar in both groups. CONCLUSION: Diclofenac suppository 50 mg and intravenous ketorolac 30 mg provided equivalent postoperative analgesia following ambulatory inguinal hernia repair under general anaesthesia. Diclofenac suppository is an economical alternative to intravenous ketorolac. In the interests of cost containment rectal diclofenac could be considered the non-steroidal anti-inflammatory drug of choice for pre-emptive analgesia.

Randomized clinical trial of postoperative subfascial infusion with bupivacaine following ambulatory open mesh repair of inguinal hernia.

BACKGROUND: Wound pain remains the commonest problem after ambulatory open repair of inguinal hernia. Postoperative subfascial infusion of the wound with bupivacaine extends local analgesia at home and may achieve superior analgesia compared with oral analgesics alone. The objective of the present trial was to evaluate the efficacy of postoperative subfascial infusion of the wound with 0.5% bupicavaine at 2 ml per hour for 48 h after operation. METHODS: Forty-four patients who underwent ambulatory open tension-free mesh hernioplasties were randomized to two arms of treatment. The pump group had an infusion pump containing 100 ml 0.5% bupivacaine being placed between the external oblique aponeurosis and the Prolene mesh, whereas the nonpump group was treated with oral analgesics alone. Assuming that an observed difference of 2.0 existed between the mean pain scores of the two groups, the estimated sample size would be at least 20 patients in each group. RESULTS: Postoperative pain scores at rest and on coughing were significantly lower in the pump group than in the nonpump group on days 0 and 1 after surgery (p < 0.01). Before being discharged, none of the pump group patients requested analgesics, but 6 patients of the nonpump group required analgesic supplement (p = 0.025). Ten patients (50%) of the pump group experienced no pain during the period of bupivacaine infusion. Recovery variables, including time taken to resume ambulation and micturition, were comparable between the two groups. The pump and nonpump group patients returned to their normal activities after a median of 3 and 4 days, respectively (p = 0.217). The postoperative morbidity rates of the two groups were similar. CONCLUSION: Postoperative subfascial infusion of the wound with 0.5% bupivacaine achieved superior analgesia compared with oral analgesics alone. Portable infusion pump is a safe technique to continue local analgesia at home after ambulatory open repair of inguinal hernia. The drawbacks of the ON-Q Pain Management System included its high cost and frequent seepage of blood-stained anesthetic fluid into the wound dressing.

Synovial chondromatosis of the foot.

Synovial chondromatosis rarely occurs in the foot. Five patients with synovial chondromatosis in the foot were treated with excision. There were four men and one woman with a mean age of 37 years (range, 19-58 years). Mineral densities adjacent to the joint were seen on radiographs of all patients. Synovial chondromatosis occurred in the calcaneocuboid, tibiotalar, naviculocuneiform, and metatarsophalangeal joints. A painful mass was the common initial presentation in all patients. The patients were followed up for an average of 5 years (range, 3-16 years) after arthrotomy and excision. All patients were relieved of symptoms and retained normal function. There was no clinical or radiographic evidence of recurrence.