Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Injectable ice slurry for reducing pericardial adipose tissue.

OBJECTIVES: Excess pericardial adipose tissue (PAT) is associated with a higher risk of cardiovascular diseases. Currently, available methods for reducing PAT volume include weight loss through diet and exercise, weight loss with medications, and bariatric surgery. However, these methods are all limited by low patient compliance to maintain the results. We have developed an injectable ice slurry that could selectively target and reduce subcutaneous adipose tissue volume. The aim of this study was to investigate the feasibility and safety of using injectable slurry to selectively reduce PAT volume in a preclinical large animal model. METHODS: PAT in Yucatan swine was injected with slurry or room temperature control solution. All animals were imaged with baseline chest computed tomography (CT) before slurry injection and at 2 months after injection to quantify PAT volume. Specimens from injected and noninjected PAT were harvested for histology. RESULTS: Slurry treatment of PAT was well tolerated in all animals. Slurry-induced selective cryolipolysis in treated PAT. CT imaging showed decrease in PAT volume in treated area at 8 weeks posttreatment compared to baseline, that was significantly different from control solution treated group (median [range]: -29.66 [-35.07 to -27.92]% vs. -1.50 [-11.69 to 8.69]% in control animals respectively, p < 0.05). CONCLUSIONS: This study demonstrated that slurry injection into PAT is feasible in a large animal model. Slurry injection was safe and effective in inducing selective cryolipolysis in PAT and reducing PAT volume. Slurry reduction of PAT could potentially serve as a novel treatment for cardiovascular diseases.

Efficacy and Safety of Laser-Assisted Combination Chemotherapy: An Explorative Imaging-Guided Treatment With 5-Fluorouracil and Cisplatin for Basal Cell Carcinoma.

BACKGROUND AND OBJECTIVES: Rising incidences of basal cell carcinoma (BCC) have increased the need for effective topical therapies. By enhancing cutaneous uptake of the chemotherapeutic agents, cisplatin and 5-fluorouracil (5-FU), laser-assisted delivery may provide a new combination treatment for BCC. Accordingly, this study aimed to evaluate tumor response, safety, and drug biodistribution in tumors and blood after topical laser-assisted 5-FU + CIS treatment in BCC patients. STUDY DESIGN/MATERIALS AND METHODS: This open-label, proof-of-concept trial investigated laser-assisted combination cisplatin + 5-FU treatment in 20 patients with histologically verified, low-risk superficial or nodular BCCs on the face (<20 mm) or trunk/extremities (<50 mm). After tumor demarcation guided by optical coherence tomography (OCT), BCCs were exposed to ablative fractional CO2 laser followed by 60 minutes topical cisplatin solution and 7-day exposure to 5% 5-FU cream under occlusion. After 30 days, treatment was repeated if any tumor residual was identified. Tumor response at day 30 and month 3 was assessed clinically as well as by OCT, reflectance confocal microscopy, and ultrasound, supplemented by histological verification at 3 months. Local skin reactions (LSRs) and side effects were evaluated on days 1, 3-5, 14, 30, and month 3. Drug detection in tumors and blood was performed in a subset of patients 1- and 24 hours after treatment. RESULTS: Nineteen patients completed the trial, with 32% (6/19) receiving a single treatment and 68% (13/19) treated twice. At 3 months, clinical clearance was seen in 18/19 patients with a corresponding 94% (17/18) achieving histological clearance. Baseline tumor thickness and subtype did not influence treatment number or clearance rate (P ≥ 0.61). LSRs were well-tolerated and consisted of erythema, edema, and erosion, followed by crusting by day 14. Erythema declined gradually by month 3, with 94% of patients and 79% of physicians rating cosmesis as "good" or "excellent." Scarring or hyperpigmentation was noted in 50% and 56%, respectively, while pain and infection were not observed during the follow-up period. Although chemotherapy uptake was visualized extending to deep skin layers, no systemic exposure to cisplatin or 5-FU was detected in patient blood. CONCLUSION: Laser-assisted cisplatin + 5-FU shows potential as an effective and tolerable treatment option for low-risk BCC, particularly in instances where self-application is not possible or where in-office, non-surgical therapy is preferred. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Hydrophilic polymer embolic complication during diagnostic cerebral angiography presenting with delayed intracranial hemorrhage: case report and literature review.

We report two serial neuroendovascular cases of hydrophilic polymer embolic complications, and highlight a unique case of a routine diagnostic cerebral angiogram that was complicated by delayed intracranial hemorrhage requiring surgical decompression. Histopathology specimens revealed organized intravascular thrombi with foci of non-polarizable, basophilic foreign material. Shavings from the hydrophilic coatings of a standard diagnostic catheter and guidewire share histologic characteristics with this intravascular foreign material, confirming the diagnosis of hydrophilic polymer emboli. While this phenomenon has been described for complex neurointerventional procedures, it is rare with routine diagnostic cerebral angiography. Along with a detailed literature review, these cases provides further evidence that even basic hydrophilic coated catheters and/or wires may contribute to the etiology of iatrogenic emboli in the neurovasculature with the potential for acute and subacute complications, requiring further investigation.

Nevi and lasers: Practical considerations.

Lasers are increasingly used for elective ablation of melanocytic nevi (MN). However, the associated risks of treating MN with lasers are debated and not well studied. Theoretical risks include inadvertently treating a melanoma mistaken for a nevus, the inability to remove all nevus cells and the possibility for residual cells to undergo malignant transformation, and the difficulty in clinically monitoring the remnant nevus for melanoma progression. Additional concerns include the morphological suitability of a lesion for laser removal and managing patients' expectations about the variable cosmetic outcomes. These potential issues have prompted us to outline some practical suggestions for clinicians and patients to consider when determining the suitability of a nevus for laser ablation. The choice to perform laser removal of a nevus is personal, both from the perspective of the treating physician and that of the person being treated. While acknowledging some uncertainty, we believe that these suggestions can help mitigate risk and improve patient outcomes. Lasers Surg. Med. 50:7-9, 2018. © 2017 Wiley Periodicals, Inc.

A case report of Hepatoid Carcinoma of the Ovary with peritoneal metastases treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy without systemic adjuvant therapy.

BACKGROUND: Hepatoid Carcinoma of the Ovary (HCO) is a rare subtype of ovarian cancers where malignant cells undergo hepatoid metamorphic changes and cytologically resemble hepatocytes. There are many case reports of HCO in the literature, and patients with these tumors are almost uniformly treated with palliative debulking and conventional adjuvant chemotherapy. To our knowledge, there is only one case report of HCO complicated by peritoneal dissemination that was treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS plus HIPEC), followed by adjuvant chemotherapy. CASE SUMMARY: A 47-year-old female presented with vague lower abdominal pain. Work-up included imaging studies and biopsies for histopathology which confirmed the diagnosis of hepatoid ovarian carcinoma with synchronous liver metastasis and peritoneal dissemination, without evidence of extraperitoneal disease. She underwent a cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS plus HIPEC) with curative intent. Complete cytoreduction was achieved (CC-0). Postoperatively, the patient elected to forgo adjuvant therapy. She continues to be closely followed through clinical and radiological surveillance. On her most recent follow-up visit, she achieved 22 months of disease-free survival. CONCLUSION: CRS plus HIPEC can be considered as a promising curative approach for HCO with peritoneal dissemination in absence of extraperitoneal disease. Further studies are warranted to determine the role of adjuvant chemotherapy in this relatively rare entity.

Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology.

Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently facilitate delivery of not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin, providing free paths for drug and vaccine delivery into the dermis while maintaining integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape-stripped skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines.

A novel laser vaccine adjuvant increases the motility of antigen presenting cells.

BACKGROUND: Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. METHODOLOGY/PRINCIPAL FINDINGS: We found that laser at a specific setting increased the motility of antigen presenting cells (APCs) and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA) effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d.) or intramuscular (i.m.) administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag)-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag(+) dendritic cells (DCs) in draining lymph nodes was significantly higher in both the 1° and 2° draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA) or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone. CONCLUSION/SIGNIFICANCE: The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants.

Apportionment of ambient primary and secondary fine particulate matter at the Pittsburgh National Energy Laboratory particulate matter characterization site using positive matrix factorization and a potential source contributions function analysis.

Fine particulate matter (PM2.5) concentrations associated with 202 24-hr samples collected at the National Energy Technology Laboratory (NETL) particulate matter (PM) characterization site in south Pittsburgh from October 1999 through September 2001 were used to apportion PM2.5 into primary and secondary contributions using Positive Matrix Factorization (PMF2). Input included the concentrations of PM2.5 mass determined with a Federal Reference Method (FRM) sampler, semi-volatile PM2.5 organic material, elemental carbon (EC), and trace element components of PM2.5. A total of 11 factors were identified. The results of potential source contributions function (PSCF) analysis using PMF2 factors and HYSPLIT-calculated back-trajectories were used to identify those factors associated with specific meteorological transport conditions. The 11 factors were identified as being associated with emissions from various specific regions and facilities including crustal material, gasoline combustion, diesel combustion, and three nearby sources high in trace metals. Three sources associated with transport from coal-fired power plants to the southeast, a combination of point sources to the northwest, and a steel mill and associated sources to the west were identified. In addition, two secondary-material-dominated sources were identified, one was associated with secondary products of local emissions and one was dominated by secondary ammonium sulfate transported to the NETL site from the west and southwest. Of these 11 factors, the four largest contributors to PM2.5 were the secondary transported material (dominated by ammonium sulfate) (47%), local secondary material (19%), diesel combustion emissions (10%), and gasoline combustion emissions (8%). The other seven factors accounted for the remaining 16% of the PM2.5 mass. The findings are consistent with the major source of PM2.5 in the Pittsburgh area being dominated by ammonium sulfate from distant transport and so decoupled from local activity emitting organic pollutants in the metropolitan area. In contrast, the major local secondary sources are dominated by organic material.

Apportionment of ambient primary and secondary fine particulate matter during a 2001 summer intensive study at the CMU Supersite and NETL Pittsburgh site.

Gaseous and particulate pollutant concentrations associated with five samples per day collected during a July 2001 summer intensive study at the Pittsburgh Carnegie Mellon University (CMU) Supersite were used to apportion fine particulate matter (PM2.5) into primary and secondary contributions using PMF2. Input to the PMF2 analysis included the concentrations of PM2.5 nonvolatile and semivolatile organic material, elemental carbon (EC), ammonium sulfate, trace element components, gas-phase organic material, and NO(x), NO2, and O3 concentrations. A total of 10 factors were identified. These factors are associated with emissions from various sources and facilities including crustal material, gasoline combustion, diesel combustion, and three nearby sources high in trace metals. In addition, four secondary sources were identified, three of which were associated with secondary products of local emissions and were dominated by organic material and one of which was dominated by secondary ammonium sulfate transported to the CMU site from the west and southwest. The three largest contributors to PM2.5 were secondary transported material (dominated by ammonium sulfate) from the west and southwest (49%), secondary material formed during midday photochemical processes (24%), and gasoline combustion emissions (11%). The other seven sources accounted for the remaining 16% of the PM2.5. Results obtained at the CMU site were comparable to results previously reported at the National Energy Technology Laboratory (NETL), located approximately 18 km south of downtown Pittsburgh. The major contributor at both sites was material transported from the west and southwest. Some difference in nearby sources could be attributed to meteorology as evaluated by HYSPLIT model back-trajectory calculations. These findings are consistent with the majority of the secondary ammonium sulfate in the Pittsburgh area being the result of contributions from distant transport, and thus decoupled from local activity involving organic pollutants in the metropolitan area. In contrast, the major local secondary sources were dominated by organic material.

Apportionment of ambient primary and secondary pollutants during a 2001 summer study in Pittsburgh using U.S. Environmental Protection Agency UNMIX.

Apportionment of primary and secondary pollutants during the summer 2001 Pittsburgh Air Quality Study (PAQS) is reported. Several sites were included in PAQS, with the main site (the supersite) adjacent to the Carnegie Mellon University campus in Schenley Park. One of the additional sampling sites was located at the National Energy Technology Laboratory, located approximately 18 km southeast of downtown Pittsburgh. Fine particulate matter (PM2.5) mass, gas-phase volatile organic material (VOM), particulate semivolatile and nonvolatile organic material (NVOM), and ammonium sulfate were apportioned at the two sites into their primary and secondary contributions using the U.S. Environmental Protection Agency UNMIX 2.3 multivariate receptor modeling and analysis software. A portion of each of these species was identified as originating from gasoline and diesel primary mobile sources. Some of the organic material was formed from local secondary transformation processes, whereas the great majority of the secondary sulfate was associated with regional transformation contributions. The results indicated that the diurnal patterns of secondary gas-phase VOM and particulate semivolatile and NVOM were not correlated with secondary ammonium sulfate contributions but were associated with separate formation pathways. These findings are consistent with the bulk of the secondary ammonium sulfate in the Pittsburgh area being the result of contributions from distant transport and, thus, decoupled from local activity involving organic pollutants in the metropolitan area.

The regional nature of PM2.5 episodes in the upper Ohio River Valley.

From October 1999 through September 2000, particulate matter (PM) with aerodynamic diameter > or =2.5 microm (PM2.5) mass and composition were measured at the National Energy Technology Laboratory Pittsburgh site, with a particle concentrator Brigham Young University-organic sampling system and a tapered element oscillating microbalance (TEOM) monitor. PM2.5 measurements had also been obtained with TEOM monitors located in the Pittsburgh, PA, area, and at sites in Ohio, including Steubenville, Columbus, and Athens. The PM data from all these sites were analyzed on high PM days; PM2.5 TEOM particulate mass at all sites was generally associated with transitions from locally high barometric pressure to lower pressure. Elevated concentrations occurred with transport of PM from outside the local region in advance of frontal passages as the local pressure decreased. During high-pressure periods, concentrations at the study sites were generally low throughout the study region. Further details related to this transport were obtained from surface weather maps and estimated back-trajectories using the hybrid single-particle Lagrangian integrated trajectory model associated with these time periods. These analyses indicated that transport of pollutants to the Pittsburgh site was generally from the west to the southwest. These results suggest that the Ohio River Valley and possible regions beyond act as a significant source of PM and its precursors in the Pittsburgh area and at the other regional sites included in this study.