An investigation of the acaricidal activity of benzyl alcohol on Rhipicephalus annulatus and Rhipicephalus sanguineus and its synergistic or antagonistic interaction with commonly used acaricides.

The most economically significant ectoparasites in the tropics and subtropics are ixodid ticks, especially Rhipicephalus annulatus and Rhipicephalus sanguineus. Years of extensive use of the readily available acaricides have resulted in widespread resistance development in these ticks, as well as negative environmental consequences. Benzyl alcohol (BA) has been frequently used to treat pediculosis and scabies, and it may be an effective alternative to commonly used acaricides. The main aim of the present study was to evaluate the acaricide activity of BA and its combination with the regularly used chemical acaricides against R. annulatus and R. sanguineus. Different concentrations of BA alone and in combination with deltamethrin, cypermethrin and chlorpyrifos were tested in vitro against adult and larvae of both tick species. The results showed that BA is toxic to R. annulatus and R. sanguineus larvae, with 100% larval mortality at concentrations of ≥50 mL/L, and LC50 and LC90 attained the concentrations of 19.8 and 33.8 mL/L for R. annulatus and 18.8 and 31.8 mL/L for R. sanguineus, respectively. Furthermore, BA in combination with deltamethrin, cypermethrin and chlorpyrifos exhibited synergistic factors of 2.48, 1.26 and 1.68 against R. annulatus larvae and 1.64, 11.1 and 1.14 against R. sanguineus larvae for deltamethrin + BA, cypermethrin + BA and chlorpyrifos + BA, respectively. BA induced 100% mortality in adult R. annulatus at concentrations of ≥250 mL/L with LC50 and LC90 reached the concentrations of 111 and 154 mL/L, respectively. Additionally, BA had ovicidal activity causing complete inhibition of larval hatching at 100 mL/L. The combination of BA with deltamethrin and cypermethrin increased acetylcholinesterase inhibition, whereas the combination of BA with chlorpyrifos decreased glutathione (GSH) activity and malondialdehyde levels. In the field application, the combination of BA 50 mL/L and deltamethrin (DBA) resulted in a significant reduction in the percentage of ticks by 30.9% 28 days post-treatment when compared with groups treated with deltamethrin alone. In conclusion, BA causes mortality in laboratory and field studies alone and in combination with cypermethrin or deltamethrin. BA can be used for control of ticks of different life stages, that is, eggs and larvae, through application to the ground.

D-limonene nanoemulsion: lousicidal activity, stability, and effect on the cuticle of Columbicola columbae.

The current study was conducted to investigate the efficacy and stability of D-limonene (DL) and its nanoemulsion (DLN) against pigeon feather lice (Columbicola columbae) and their mode of action. DL pure form and DLN were prepared and characterized freshly and after storage for 50 days. In vitro bioassay on live lice was conducted with different concentrations of DL, DLN, and deltamethrin (DM). The results revealed significant mortality rates in the DL-, DLN-, DM-treated groups when compared with the control (p < 0.05). The scanning electron micrographs of lice treated with DL and DLN revealed collapsed bodies with destruction in the cuticle of the mouthparts and damaged antennae. The 50 days stored DLN showed stability in their effectiveness when compared with the freshly prepared formulation. DL and DLN caused significant inhibition (p ≤ 0.05) in acetylcholinesterase activity (AchE). Malondialdehyde level (MDA) was significantly increased while glutathione was significantly decreased in DL- and DLN-treated lice. In conclusion, DL and DLN have significant lousicidal activities. DLN showed better stability than DL after storage for 50 days. In addition, the mode of action of DL may associate with its effect on the cuticle of the lice body, inhibition of AchE, and increasing oxidative stress in the treated lice.

Role of antioxidant activity of essential oils in their acaricidal activities against Rhipicephalus annulatus.

Essential oils of Origanum majorana and Satureja thymbra as well as carvacrol are natural products that are known to have potent antioxidant activities. The current study was designed to investigate the role of the antioxidant properties of these natural products in their acaricidal activities against Rhipicephalus annulatus larvae. The synergistic and/or antagonistic effects of the addition of vitamins E and C and hydrogen peroxide (H2O2) to these natural products were also evaluated. Larval packet tests were used to evaluate the acaricidal activities against the larvae of R. annulatus. The antioxidant effectiveness of these products was determined by a DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. The addition of vitamin E at 100 mg/mL to O. majorana and S. thymbra decreased the concentrations required to achieve the death of half of the larvae (LC50) to 0.44 and 0.47%, respectively. The combination of O. majorana and S. thymbra attained the LC50 at 1.54% which was decreased to 0.69% after addition of vitamin E. Also, the addition of vitamin E to carvacrol reduced the LC50 to 0.27%. The total antioxidant activity of these natural products increased significantly in presence of vitamin E. The addition of H2O2 inhibited the acaricidal activity of all tested materials, especially at low concentrations. All treatments induced an increase in lipid peroxidation, whereas carvacrol-treated larvae revealed the lowest values for the superoxide dismutase. Glutathione peroxidase and catalase activity decreased in larvae treated with S. thymbra combined with vitamin E. In conclusion, the addition of vitamins E and C increased the acaricidal activities of the tested compounds, whereas the addition of H2O2 decreased these activities. The antioxidant activities of essential oils and their active components may play an important role in mediating their acaricidal activities.

Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort. PATIENTS AND METHODS: We conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors. RESULTS: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4-12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19-2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs. CONCLUSIONS: Presence of bone metastases at baseline was associated with a worse prognosis for patients with mNSCLC treated with ICI after controlling for multiple clinical characteristics. Use of BMAs was not associated with reduced SREs or a difference in survival.

Optimal Data Collection Time in LoRa Networks-A Time-Slotted Approach.

LoRa is a low-power and long range radio communication technology designed for low-power Internet of Things devices. These devices are often deployed in remote areas where the end-to-end connectivity provided through one or more gateways may be limited. In this paper, we examine the case where the gateway is not available at all times. As a consequence, the sensing data need to be buffered locally and transmitted as soon as a gateway becomes available. However, due to the Aloha-style transmission policy of current LoRa-based standards, such as the LoRaWAN, delivering a large number of packets in a short period of time by a large number of nodes becomes impossible. To avoid bursts of collisions and expedite data collection, we propose a time-slotted transmission scheduling mechanism. We formulate the data scheduling optimisation problem, taking into account LoRa characteristics, and compare its performance to low complexity heuristics. Moreover, we conduct a set of simulations to show the benefits of synchronous communications on the data collection time and the network performance. The results show that the data collection can reliably be achieved at least 10 times faster compared to an Aloha-based approach for networks with 100 or more nodes. We also develop a proof-of-concept to assess the overhead cost of communicating the schedule to the nodes and we present experimental results.

Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population.

Although inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab, the mechanisms mediating this resistance remain elusive. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrate that development of trastuzumab resistance in these cells is mediated by activation of an IL6 inflammatory feedback loop leading to expansion of the cancer stem cell (CSC) population. Long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL6 than parental cells. An IL6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies demonstrate that trastuzumab resistance may be mediated by an IL6 inflammatory loop and suggest that blocking this loop may provide alternative strategy to overcome trastuzumab resistance.

Cutaneous squamous cell carcinoma progression is associated with decreased GATA-3 immunohistochemical staining.

BACKGROUND: The GATA family of transcription factors is an essential regulator of cellular proliferation and differentiation. In the skin, GATA-3 is critical for epidermal stratification and maintenance of barrier function. A role for GATA-3 in the development of human cutaneous squamous cell carcinoma (SCC) is not known. Here, we investigated GATA-3 immunohistochemical staining in premalignant and invasive cutaneous SCC from sun-exposed and sun-protected skin. METHODS: GATA-3 immunohistochemistry was performed on actinic keratoses (AK) (n = 19), in situ squamous cell carcinomas with actinic [SCCIS (A)] (n = 9) or bowenoid features [SCCIS (B)] (n = 17), well-, moderately and poorly differentiated SCC (n = 36), Bowenoid papulosis of the perineum (n = 15) and penile SCC (pSCC) (n = 10). RESULTS: We found that GATA-3 immunohistochemical staining is progressively lost in sun-exposed skin as neoplasia progresses from pre-cancerous AK to SCCIS (A), and ultimately, to SCC, which shows near absent GATA-3 staining. This reduction in GATA-3 staining is independent of histological grade in SCC. Only slight down-regulation of GATA-3 was seen in all cases of SCCIS (B) and Bowenoid papulosis, while near absent GATA-3 expression was seen in pSCC. CONCLUSION: We propose that decreased GATA-3 immunohistochemical staining is associated with cutaneous SCC progression on both sun-exposed and sun-protected sites.

Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

Biphasic Sarcomatoid Porocarcinoma.

Sarcomatoid carcinomas are rare malignant tumors, which usually demonstrate a well-differentiated epithelial component in association with a poorly differentiated spindle-cell component. Several different subtypes have been reported and categorized primarily under the differentiated epithelial component, with the majority of cutaneous sarcomatoid carcinomas arising in the setting of a basal cell or squamous cell carcinoma. To date, only 4 cases of sarcomatoid porocarcinoma have been reported in the literature. The authors present a case of an 84-year-old woman with an ulcerated papule on her scalp for several months. Histopathology revealed an exophytic and endophytic epidermal proliferation with multiple mitoses and ductal differentiation overlying a poorly differentiated, infiltrative spindle-cell proliferation in the dermis. Ductal and cystic structures were scattered throughout the malignancy. Immunohistochemistry was notable for strong and diffuse pancytokeratin positivity, p63 positivity, focally positive carcinoembryonic antigen within the ductal lumina, and periodic acid-schiff-positive, diastase-resistant intracellular deposits. They present the findings of this rare case of primary cutaneous sarcomatoid porocarcinoma.

Anterior versus posterior approach in surgical treatment of tuberculous spondylodiscitis of thoracic and lumbar spine.

PURPOSE: The aim of this study is to compare the clinical, radiological and functional outcome of anterior versus posterior surgical debridement and fixation in patients with thoracic and lumbar tuberculous spondylodiscitis. PATIENTS AND METHODS: A total number of 42 patients with tuberculous spondylodiscitis of the thoracic and lumbar spine treated surgically were included in this study. Twenty patients (group A) underwent anterior debridement, decompression and instrumentation by anterior approach. Twenty-two patients (group B) were operated by posterolateral (extracavitary) decompression and posterior instrumentation. Operative parameters, clinical, radiographic and functional results for the two groups were analyzed and compared. RESULTS: The average follow-up period was 15 months (range 12-24) in both groups. The average operative time, blood loss and blood transfusion of anterior group were significantly less than the posterior one. There was significant better back pain relief, kyphotic angle correction and less angle loss in the posterior group than anterior. There was no significant difference between the two groups regarding neurological recovery, functional outcome and fusion rate. CONCLUSION: Both anterolateral and posterolateral approaches are sufficient for achieving the goals of surgical treatment of thoracic and lumbar Pott's disease but posterolateral approach allows significant better kyphotic angle correction, less angle loss, better improvement in back pain but unfortunately more operative time and blood loss.

Pathogenicity and phenotypic characterization of enterotoxigenic Escherichia coli isolates from a birth cohort of children in rural Egypt.

Enterotoxigenic Escherichia coli (ETEC) has consistently been the predominant bacterial cause of diarrhea in many birth cohort- and hospital-based studies conducted in Egypt. We evaluated the pathogenicity of ETEC isolates in a birth cohort of children living in a rural community in Egypt. Between 2004 and 2007, we enrolled and followed 348 children starting at birth until their second year of life. A stool sample and two rectal swabs were collected from children during twice-weekly visits when they presented with diarrhea and were collected every 2 weeks if no diarrhea was reported. From routine stool cultures, five E. coli-like colonies were screened for ETEC enterotoxins using a GM1 enzyme-linked immunosorbent assay (ELISA). The isolates were screened against a panel of 12 colonization factor antigens (CFAs) by a dot blot assay. A nested case-control study evaluated the association between initial or repeat excretion of ETEC and the occurrences of diarrhea. The pathogenicity of ETEC was estimated in symptomatic children compared to that in asymptomatic controls. ETEC was significantly associated with diarrhea (crude odds ratio, 1.37; 95% confidence interval [CI], 1.24 to 1.52). The distribution of ETEC enterotoxins varied between the symptomatic children (44.2% heat-labile toxin [LT], 38.5% heat-stable toxin [ST], and 17.3% LT/ST) and asymptomatic children (55.5% LT, 34.6% ST, and 9.9% LT/ST) (P < 0.001). The CFAs CFA/I (n = 61), CS3 (n = 8), CS1 plus CS3 (n = 24), CS2 plus CS3 (n = 18), CS6 (n = 45), CS5 plus CS6 (n = 11), CS7 (n = 25), and CS14 (n = 32) were frequently detected in symptomatic children, while CS6 (n = 66), CS12 (n = 51), CFA/I (n = 43), and CS14 (n = 20) were detected at higher frequencies among asymptomatic children. While all toxin phenotypes were associated with diarrheal disease after the initial exposure, only ST and LT/ST-expressing ETEC isolates (P < 0.0001) were associated with disease in repeat infections. The role of enterotoxins and pathogenicity during repeat ETEC infections appears to be variable and dependent on the coexpression of specific CFAs.

Ponatinib-induced neutrophilic panniculitis.

Ponatinib is a bcr-abl tyrosine-kinase inhibitor (TKI) used to treat resistant and refractory chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia that express bcr-abl. Neutrophilic panniculitis has been described in rare cases of patients on other TKIs in the same class as ponatinib. We present the first case of neutrophilic panniculitis following treatment with ponatinib and summarize the other cases of panniculitis caused by TKIs.

Autofusion in growing rod surgery for early onset scoliosis; what do we know so far?

The evolving landscape of early onset scoliosis management has shifted from the traditional paradigm of early definitive spinal fusion towards modern growth-friendly implants, particularly Growing Rods (GR). Despite the initial classification of GR treatment as a fusionless procedure, the phenomenon of autofusion has emerged as a critical consideration in understanding its outcomes. Studies have demonstrated the presence of autofusion since the early 1980s. The consequences of autofusion are extensive, impacting curve correction, diminishing trunk growth rate, and contributing to the "law of diminishing returns" in growing rod surgery. The literature suggests that autofusion may complicate definitive fusion surgery, leading to prolonged and intricate procedures involving multiple osteotomies. Additionally, it poses challenges in identifying anatomical landmarks during surgery, potentially increasing the risk of complications and revisions. While autofusion poses challenges to achieving optimal outcomes in growing rod treatment, it cannot be considered a standalone replacement for definitive fusion. Recent advances aim to limit autofusion and enhance treatment outcomes. In this review, we will delve into the existing literature on autofusion, examining studies that have documented its presence, probable causes, pathophysiology, potential implications for long-term patient outcomes, and possible new implants and techniques that decrease its incidence.

A Saudi Woman with Ceftriaxone Induced Fixed Drug Eruption.

Background: A fixed drug eruption (FDE) is an immunological cutaneous adverse reaction, classified as a cutaneous adverse drug reaction (CADR) and characterized by well-defined lichenoid lesions that occur at the same site each time. Ceftriaxone is a third-generation antibiotic of cephalosporin antibiotics of the beta-lactam antibiotic family, which has typical in vitro activity against many Gram-negative aerobic bacteria. This is the first clinical case from Saudi Arabia and the fifth in the world to document a woman's experience with recurrent FDE after repeated ceftriaxone use. Case Report. A 25-year-old Saudi woman with a known case of sickle cell anemia (SCA) with a history of avascular necrosis of the right hip after replacement was hospitalized with a pain crisis triggered by an upper respiratory tract infection. The patient denied having a history of allergy previously. Due to fever, leukocytosis, and active follicular tonsillitis, ceftriaxone was started. However, a few hours later she developed lip edema and a fixed drug eruption measuring 7 × 11 cm on the left side of her back. The lesion reformed over a hyperpigmented lesion (4 × 8 cm) that the patient did not report upon initial examination. It turned out that this was due to the intravenous administration of ceftriaxone, a year ago in another hospital. An allergy to ceftriaxone was considered, and steroids and antihistamines were started. The case was labeled as ceftriaxone induced FDE. Conclusion: Ceftriaxone induced FDE is an uncommon type of allergic reaction that has been reported infrequently. Understanding this condition and the mechanism by which FDE becomes recurrent with the same previous fixed lesion is of great importance for both academic and future research purposes.

The Outcome of the WALANT Technique in Primary Hand Flexor Tendons Repair.

Introduction: Wide-awake local anesthesia and no tourniquet (WALANT) represents a revolutionary technique for hand surgeons who dismiss tourniquets and sedation. In this study, we present our experience with the WALANT technique in primary flexor tendon injuries of the hand. Patient and methods: This prospective research was carried out on 30 patients undergoing hand primary, flexor tendon repair surgery. Flexor tendon injury zones 2, 3, 4, and 5 were included. WALANT was prepared and injected. The tendons were surgically managed by a cruciate single cross-stitched locked 4-strand technique. The pain was assessed using a visual analog scale (VAS) score. The range of motion (ROM) of affected fingers was assessed according to the Strickland evaluation system. Results: There was a highly significant relationship between the patient's compliance with physiotherapy and obtained ROM of the affected finger with a P value <0.001. During injection of WALANT solution, 4 cases (13.3%) had no pain, 25 cases (83.3%) had mild pain (score 1-4), and 1 case (3.3%) had moderate pain (score 5-7). Conclusion: WALANT provides an optimal bloodless and comfortable field with an opportunity to assess the strength of tendon repair, gapping or triggering and managing them intra-operatively.

Posterolateral Fusion Versus Posterior Lumbar Interbody Fusion for Adult Low-Grade Isthmic Spondylolisthesis: Analysis of Sagittal Radiographic Parameters - A Randomized Controlled Trial.

STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To compare the effect of posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) on sagittal radiographic parameters in patients with low-grade isthmic spondylolisthesis. Additionally, to explore the correlation between changes in these parameters and clinical outcomes. METHODS: Forty-six consecutive patients with single-level low-grade isthmic spondylolisthesis were initially enrolled. They were randomly assigned to undergo either PLF or PLIF. Patients were followed up for at least 24 months. Radiographic outcomes included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, sagittal vertical axis, T1 pelvic angle, slip angle, slip degree and disc height. Clinical outcomes were assessed by the Oswestry Disability Index (ODI) and visual analogue scale (VAS). RESULTS: Four participants were lost to follow-up. Of the remaining 42 patients, 29 were female. The mean age was 40.23 ± 10.25 years in the PLF group and 35.81 ± 10.58 years in the PLIF group. There was a statistically significant greater correction of all radiographic parameters in the PLIF group. The ODI and VAS improved significantly in both groups, with no significant differences between the two groups. Changes in the ODI and VAS were significantly correlated with changes in disc height, slip angle and lumbar lordosis. CONCLUSIONS: In patients with low-grade isthmic spondylolisthesis, PLIF demonstrates superior efficacy compared to PLF in correcting sagittal radiographic parameters. Nevertheless, this distinction does not seem to influence short-term clinical results. Restoring disc height, correcting the slip angle, and reestablishing normal lumbar lordosis are crucial steps in the surgical management of isthmic spondylolisthesis.

Frankincense-Based Functionalized Multiwalled Carbon Nanotubes with Iron Oxide Composites for Efficient Removal of Crystal Violet: Kinetic and Equilibrium Analysis.

In this study, novel adsorbents were developed by functionalizing multiwalled carbon nanotubes with frankincense (Fr-fMWCNT) and adding iron oxide (Fe3O4) to the adsorbent (Fr-fMWCNT-Fe3O4). The morphology, surface characteristics, and chemical nature of the synthesized samples were analyzed by using various characterization techniques. The prepared adsorbents were then applied for the elimination of the toxic dye, crystal violet (CV), from water-based solutions by employing a batch adsorption method. The effectiveness of materials for the adsorption of CV was investigated by tuning various effective experimental parameters (adsorbent dosage, dye quantity, pH, and contact time). In order to derive adsorption isotherms, the Langmuir and Freundlich adsorption models were investigated and compared. The Fr-fMWCNT and Fr-fMWCNT-Fe3O4 were found to remove 85 and 95% of the CV dye within 30 min of the adsorption experiment at pH 6, respectively. It was found that a pseudo-second-order reaction rate was consistent with the experimental adsorption kinetics. The equilibrium data demonstrated that the Langmuir model adequately explained the adsorption behavior of the CV dye on the Fr-fMWCNT and Fr-fMWCNT-Fe3O4 surfaces, respectively. According to the Langmuir study, the highest adsorption capacities of the dye are 434 mg/g for Fr-fMWCNT and 500 mg/g for Fr-fMWCNT-Fe3O4. Remediation of the CV dye using our novel composite materials has not been reported previously in the literature. The synthesized Fr-fMWCNT and Fr-fMWCNT-Fe3O4 adsorbents can be economical and green materials for the adsorptive elimination of CV dye from wastewater.

Quantitative near infrared spectroscopic analysis of Q-Switched Nd:YAG treatment of generalized argyria.

BACKGROUND AND OBJECTIVE: Generalized argyria is a blue-gray hyperpigmentation of the skin resulting from ingestion or application of silver compounds, such as silver colloid. Case reports have noted improvement after Q-Switched Neodymium-Yttrium Aluminum Garnet laser (1,064 nm QS Nd:YAG) laser treatment to small surface areas. No reports have objectively monitored laser treatment of generalized argyria over large areas of skin, nor have long-term outcomes been evaluated. STUDY DESIGN/MATERIALS AND METHODS: An incremental treatment plan was developed for a subject suffering from argyria. A quantitative near infrared spectroscopic measurement technique was employed to non-invasively analyze tissue-pigment characteristics pre- and post-laser treatment. Post-treatment measurements were collected at weeks 1, 2, 3, and 4, and again at 1 year. RESULTS: Immediate apparent removal of pigment was observed with 1 Q-switched 1,064 nm Nd:YAG laser treatment (3-6 mm spot; 0.8-2 J/cm(2) ) per area. Entire face, neck, upper chest, and arms were treated over multiple sessions. Treatments were very painful and general anesthesia was utilized in order to treat large areas. Near-infrared spectroscopy was used to characterize and quantify the concentration of silver particles in the dermis based on the absorption features of the silver particles as well as the optical scattering effects they impart. We were able to estimate that there was, on average, 0.042 mg/ml concentration of silver prior to treatment and that these levels went below the minimum detectable limit of the instrument post-treatment. There was no recurrence of discoloration over the 1-year study period. CONCLUSION: QS 1,064 nm laser treatment of argyria is a viable method to restore normal skin pigmentation with no evidence of recurrence over study period. Quantitative spectroscopic measurements: (1) confirmed dyspigmentation was due to silver, (2) validated our clinical assessment of no recurrence up to 1-year post-treatment, and (3) indicated no collateral tissue damage with treatments.

Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab.

BACKGROUND: Often, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population. Here, we present survival outcomes associated with pembrolizumab for R/R NSCLC. MATERIALS AND METHODS: We retrospectively assessed adults with NSCLC who received pembrolizumab for R/R disease between January 2016 to January 2023. Primary objective was to estimate OS and PFS in this cohort compared to historical outcomes. Secondary objective was to compare OS and PFS among subgroups. RESULTS: Fifty patients were evaluated. Median follow-up time was 11.3 months (2.9-38.2). OS was 10.6 months (95% CI, 8.8-19.2); 1-year OS rate 49% (95% CI, 36 - 67%). PFS was 6.1 months (95% CI, 4.7-9.0); 1-year PFS rate 25% (95% CI, 15%-42%). Current smokers had significantly better median OS/PFS as compared to former smokers (NA vs. 10.5 and 9.9 vs. 6.0 months, respectively). The addition of chemotherapy demonstrated an OS benefit (median OS 12.9 vs. 6.0 months) but was not statistically significant. CONCLUSION: Patients with R/R NSCLC represent a distinct cohort with inferior survival outcomes when compared to those with de novo stage IV disease treated with pembrolizumab-based regimens. Based on our findings, we recommend oncologists exercise caution when considering checkpoint inhibitor monotherapy in the front-line setting for R/R NSCLC, regardless of PD-L1 expression.