Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

A Pilot Study of Hepatic Irradiation with Yttrium-90 Microspheres Followed by Immunotherapy with Ipilimumab and Nivolumab for Metastatic Uveal Melanoma.

Background: Liver metastases from uveal melanoma carry a very poor prognosis. Hepatic artery infusions with Yttrium-90 (90Y) resin microspheres have some activity in this disease, and radiation and immunotherapy may be synergistic. The primary objective of this study was to determine the safety and tolerability of sequential 90Y resin microspheres and immunotherapy with ipilimumab and nivolumab in metastatic uveal melanoma. Materials and Methods: Twenty-six patients with uveal melanoma with hepatic metastases were entered into a pilot study. Treatment consisted of two infusions of 90Y resin microspheres, one to each lobe of the liver, followed in 2-4 weeks by immunotherapy with ipilimumab and nivolumab every 3 weeks for four doses, then maintenance immunotherapy with nivolumab alone. Results: Initial dosing of both 90Y and immunotherapy resulted in excessive toxicity. With decreasing the dosage of 90Y to limit the normal liver dose to 35Gy and lowering the ipilimumab dose to 1 mg/kg, the toxicity was tolerable, with no apparent change in efficacy. There was one complete and four confirmed partial responses, for an objective response rate of 20% and a disease control rate of 68%. The median progression-free survival was 5.5 months (95% confidence interval [CI]: 1.3-9.7 months), with a median overall survival of 15 months (95% CI: 9.7-20.1 months). Conclusions: With dose reductions, sequential therapy with 90Y and immunotherapy with ipilimumab and nivolumab is safe and tolerable, and has activity in metastatic uveal melanoma. These results justify a controlled trial to demonstrate whether 90Y resin microspheres add to the utility of combination immunotherapy in this disease. Clinical Trial Registration number: NCT02913417.

The meaning of scientific objectivity and subjectivity: From the perspective of methodologists.

Given the challenges to the notion of objectivity posed by social psychological research on investigator effects, constructivist and critical epistemological perspectives, and the introduction of qualitative research methods in psychology, the investigators examined how leading methodologists understand the function of objectivity and subjectivity in psychological science. The aim of the study was to learn how contemporary methodologists view these issues so as to communicate converging perspectives to the field and inform methods education. A brief historical review of the concept of objectivity in psychology is presented to contexualize this examination. Eleven accomplished methodologists with expertise in a range of methods and epistemological perspectives were interviewed. Findings from a grounded theory analysis demonstrated that all the participants expressed concern about the belief that science is unaffected by scientists' perspectives, believing researchers and educators should problematize this perspective. Recommendations from participants included that science be viewed as a value-laden endeavor in which scientists systematically conduct research from multiple epistemological perspectives, and/or utilize diverse methods tailored to address their questions. Scientific procedures were detailed that could curtail dangers of either unchecked subjectivity or a false sense of objectivity. A functional analysis of these constructs, objectivity and subjectivity, suggested they both serve a similar scientific and an ethical purpose-to prevent the premature foreclosure of possible understanding because of the expectations of researchers. The mainstreaming of disclosures about the perspectives and positions of investigators, as well as their management, and the implementation of epistemological and methodological pluralism are encouraged to support this ethic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The lymphatic system and sentinel lymph nodes: conduit for cancer metastasis.

The lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.

How to become a responsive therapist: A study of experiences of developing therapists.

OBJECTIVE: : A growing body of empirical evidence suggests that psychotherapy is more effective when therapists tailor interventions to fit their specific clients' needs, a concept referred to as therapist responsiveness in the psychotherapy literature. However, the question of how therapists learn to become responsive rarely has been examined. METHOD: : The central question of this study, put to eleven graduate student therapist trainees, was, "How did you learn to be responsive to clients as a novice therapist, and in what ways have you become responsive?" A critical-constructivist grounded theory method was employed to generate themes from trainees' replies. RESULTS: : The analysis showed that trainees learned to improve their responsiveness to clients by: (1) becoming more aware of cues that signaled the need to adapt interventions (as related to psychotherapy change processes, client-therapist relational dynamics, clients' identities and cultural contexts, and the maximizing of clients' agency); (2) developing attunement to their own emotions and engaging in self-care; and (3) adopting mindsets that facilitated their trying new relational or therapy approaches while also maintaining professionalism. CONCLUSION: Based upon these findings, preliminary suggestions for responsiveness training are presented to guide programs that wish to train responsive psychotherapists .

Macular laser photocoagulation in the management of diabetic macular edema: Still relevant in 2020?

Macular laser photocoagulation (MLP) is inferior to intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of center-involved diabetic macular edema (DME). Ultra-widefield fluorescein angiography-guided laser photocoagulation to presumed ischemic areas of the peripheral retina or MLP do not reduce the treatment burden nor improve the visual outcomes of eyes treated with anti-VEGF drugs. Destruction of retinal tissue is not necessary to induce a therapeutic response in DME. Modern lasers are capable of producing invisible laser "burns" that do not destroy the targeted tissue using micropulse subthreshold (ST) mode where the laser's duty cycle is modified or alternatively selective retinal therapy (SRT) where ultrashort pulses of continuous wave laser selectively target the RPE. The best results with micropulse ST laser are obtained in eyes with a central macular thickness ≤400 µm. Eyes need to be treated in a continuous manner with no spaces between burns in the edematous area. Micropulse ST-MLP downregulates inflammatory biomarkers produced by activated microglial cells and Müller cells. Micropulse ST-MLP may reduce the anti-VEGF injection burden in DME. In SRT, the diseased RPE is targeted and heated with the laser with the hope that the adjacent RPE migrates and proliferates into these areas to heal the diseased RPE. There is much less experience with SRT, but the results are promising and deserve further study.

Susac's syndrome: an update.

Susac's syndrome (SS) is a relatively rare cause of multiple recurrent branch retinal arterial occlusions (BRAO). SS is frequently misdiagnosed and probably underdiagnosed. Ophthalmic manifestations may be the sole presenting sign of SS. Comprehensive literature review The typical triad of encephalopathy, sensorineural hearing loss and multiple recurrent BRAO is seldom seen at presentation in SS. The characteristic ophthalmological feature in SS is the presence of recurrent multiple BRAO in the absence of intraocular inflammation. Yellow to yellow-white, non-refractile or refractile retinal arterial wall plaques (Gass plaques) found at midarteriolar segments not associated to bifurcations are commonly found in SS. Because of its ability to capture more peripheral retinal area, ultrawide field fluorescein angiography (FA) has definite advantages over conventional FA and its use should be encouraged in patients suspected of having SS. Optical coherence tomography (OCT), particularly spectral domain OCT complements FA. Patients with BRAO and hearing loss that do not develop encephalopathy during the initial 2 years will most likely not develop encephalopathy. However, these patients will be prone to recurrent BRAO and hearing loss. Imunosuppression is the cornerstone of treatment but the best regimen still needs to be defined. A minority of patients with SS present with the typical triad. A high index of suspicion is needed to make the diagnosis promptly. Early diagnosis and treatment are important to delay disease progression and prevent blindness, deafness and dementia.

Correction to: Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery.

The article "Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery," written by Stanley P. Leong et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on August 13, 2018, without open access.

Vascular endothelial growth factor inhibition and proliferative diabetic retinopathy, a changing treatment paradigm?

Prior to the development of panretinal photocoagulation (PRP) in the 1970s, proliferative diabetic retinopathy (PDR) was the most common cause of blindness in diabetic patients. The diabetic retinopathy study demonstrated that PRP could decrease severe visual loss from PDR by 50%. Since then and for the past four decades, PRP has been the treatment of choice for eyes with PDR. In the past decade, vascular endothelial growth factor (VEGF) inhibition has become the treatment of choice for diabetic macular edema (DME). When treated intensively with anti-VEGF drugs, about one-third of eyes with DME experience an improvement in their diabetic retinopathy severity scale. Randomized clinical trials comparing ranibizumab to PRP and aflibercept to PRP have shown that VEGF inhibitors cause regression of intraocular neovascularization but need to be given on a fairly regular basis. Despite these promising results, concerns about treatment adherence have surfaced. Patients with PDR that are treated solely with anti-VEGF drugs and somehow interrupt their treatment are at a high risk of developing irreversible blindness. Combination treatment of PRP plus an anti-VEGF drug may be the treatment of choice for PDR.

Corticosteroids for Diabetic Macular Edema.

Diabetic macular edema (DME) is a chronic condition with a multifactorial pathogenesis. Vascular endothelial growth factor (VEGF) and several inflammatory mediators are upregulated in eyes with DME. VEGF inhibitors and corticosteroids have all been used successfully in the management of DME. Currently available corticosteroids include triamcinolone acetonide (TA), the dexamethasone (DEX) intravitreal implant, and the fluocinolone acetonide (FA) intravitreal implant. The response to treatment can vary substantially with each treatment modality. Some cases of DME are VEGF driven, and in others, inflammation plays a key role. Chronicity appears to favor corticosteroid treatment. There are no clear guidelines to guide switching from an anti-VEGF to a corticosteroid. Combination therapy of an anti-VEGF drug and a corticosteroid does not appear to provide additional benefit over monotherapy with either drug. The main advantage of corticosteroids over VEGF inhibitors is their longer duration of action. Vitrectomy does not affect the pharmacokinetics of the corticosteroid implants. Common adverse events of corticosteroids include cataract formation, cataract progression, and ocular hypertension. TA may cause a sterile endophthalmitis and pseudoendophthalmitis. Migration of the intravitreal DEX and FA implants into the anterior chamber can be problematic. Because of their less favorable safety profile, corticosteroids are generally used as a second-line treatment for DME. Advantages of using an intravitreal corticosteroid implant include the reduction of treatment burden and predictable pharmacokinetics even in vitrectomized eyes. Pseudophakic eyes, previously vitrectomized eyes and eyes with long-standing DME, particularly of patients who have difficulty in maintaining a monthly appointment, may benefit from primary treatment with a corticosteroid intravitreal implant.

Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative Rate for Melanoma Sentinel Lymph Node Surgery.

BACKGROUND: Preoperative imaging and intraoperative gamma probe (GP) localization is standard for identifying sentinel lymph nodes (SLNs) in melanoma patients. The aim of this prospective Institutional Review Board-approved study was to investigate whether an intraoperative portable gamma camera (PGC) improves SLN detection over the GP. METHODS: Lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed after injection of 99mTc-Tilmanocept in melanoma patients (≥ 18 years, Breslow thickness ≥ 1.0 mm). A GP was used to localize the SLNs in each basin, which was explored by the GP to ensure that the operative field was < 10% counts of the hottest SLN. The PGC was then used after a negative GP screening. Any residual hotspots identified by the PGC were considered as additional SLNs and were removed following the 10% rule. RESULTS: Preoperative imaging of 100 patients identified 138 SLN basins, with 306 SLNs being identified by conventional surgery. The PGC localized 89 additional SLNs in 54 patients. Thus, the PGC identified an additional 23% of SLNs [95% confidence interval (CI) 18-27%]. Four of these 89 SLNs showed micrometastasis in four patients, in two of whom the only tumor-positive SLN was identified by the PGC, preventing two false-negative cases. Thus, the null hypothesis that the PGC did not detect additional positive SLNs was rejected (p = 0.000). The overall SLN positive rate was 9.9% (39/395, 95% CI 6-12), and the overall patient positive rate was increased using the PGC, from 25 to 27% (27/100). CONCLUSIONS: Intraoperative PGC imaging yielded additional SLNs in a significant number of patients over GP alone. Identification of these additional SLNs resulted in upstaging of four patients with two patients being converted from a negative to a positive status, thus, preventing two false-negative cases.

Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies.

BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Acute visual loss and intraretinal hemorrhages associated to energy drink consumption.

PURPOSE: To report the association of acute visual loss secondary to intraretinal hemorrhages and energy drink consumption. METHODS: Case report and literature review. RESULTS: A 48-year-old hypertensive man developed an elevation in systemic blood pressure, tachycardia, and acute visual loss secondary to intraretinal hemorrhages shortly after drinking several cans of energy drinks. CONCLUSION: High consumption of energy drinks may lead to intraretinal hemorrhages and acute visual loss.

Prediction of positron emission tomography/computed tomography (PET/CT) positivity in patients with high-risk primary melanoma.

Positron emission tomography/computed tomography (PET/CT) is an important tool to identify occult melanoma metastasis. To date, it is controversial which patients with primary cutaneous melanoma should have staging PET/CT. In this retrospective analysis of more than 800 consecutive patients with cutaneous melanoma, we sought to identify factors predictive of PET/CT positivity in the setting of newly-diagnosed high-risk primary melanoma to determine those patients most appropriate to undergo a PET/CT scan as part of their diagnostic work up. 167 patients with newly-diagnosed high-risk primary cutaneous melanoma underwent a PET/CT scan performed as part of their initial staging. Clinical and histologic factors were evaluated as possible predictors of melanoma metastasis identified on PET/CT scanning using both univariate and multivariate logistic regression. In all, 32 patients (19.2%) had a positive PET/CT finding of metastatic melanoma. In more than half of these patients (56.3%), PET/CT scanning identified disease that was not detectable on clinical examination. Mitotic rate, tumor thickness, lymphadenopathy, and bleeding were significantly predictive of PET/CT positivity. A combinatorial index constructed from these factors revealed a significant association between number of high-risk factors observed and prevalence of PET/CT positivity, which increased from 5.8% (with the presence of 0-2 factors) to 100.0%, when all four factors were present. These results indicate that combining clinical and histologic prognostic factors enables the identification of patients with a higher likelihood of a positive PET/CT scan.

Microbial recovery from clot-activating Vacutainers®.

Biological specimens for microbiological analysis are often collected in BD Vacutainers®, which are not specifically designed for microbial recovery. Bacterial and fungal recovery was analyzed for glass and plastic tubes with or without clot-activating silica. No significant impact was found for the recovery of most bacteria and yeasts tested, however, Haemophilus influenzae recovery from cerebrospinal fluid was significantly reduced in both glass and plastic clot activator tubes.

In Vitro Antimicrobial Susceptibility of Staphylococcus pseudintermedius Isolates of Human and Animal Origin.

MIC results for 115 Staphylococcus intermedius group isolates are presented. Of these, 33% were methicillin resistant, among which 51.4% were susceptible to doxycycline, 29.7% to clindamycin, and 21.6% to trimethoprim-sulfamethoxazole. All of the isolates were susceptible to ceftaroline, daptomycin, linezolid, nitrofurantoin, quinupristin-dalfopristin, rifampin, tigecycline, and vancomycin. Of all the isolates, 82.6%, 67.8%, and 23.5% were susceptible to ciprofloxacin, erythromycin, and penicillin, respectively. No isolates harbored mupA or qacA/B genes, which suggested a lack of resistance to mupirocin or chlorhexidine.

Comparison of the Vitek MS and Bruker Microflex LT MALDI-TOF MS platforms for routine identification of commonly isolated bacteria and yeast in the clinical microbiology laboratory.

This study compared the diagnostic performance of Bruker's Microflex LT and bioMérieux's Vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry systems. A total of 477 isolates were tested on both instruments. Discrepant results were resolved by sequencing. Overall, there was no statistically significant difference between the proportion of isolates correctly identified, miscalled or not called by each instrument. Although both systems were good at identifying yeast (66/69 to species level), the confidence level was high only to genus level for 30% of the isolates on the Bruker. Both systems performed with high accuracy when evaluated solely on Food and Drug Administration-approved organisms for each database. A user-based assessment of the 2 instruments revealed an overall preference for the Vitek MS instrument.

Detection of intestinal protozoa in the clinical laboratory.

Despite recent advances in diagnostic technology, microscopic examination of stool specimens remains central to the diagnosis of most pathogenic intestinal protozoa. Microscopy is, however, labor-intensive and requires a skilled technologist. New, highly sensitive diagnostic methods have been developed for protozoa endemic to developed countries, including Giardia lamblia (syn. G. intestinalis/G. duodenalis) and Cryptosporidium spp., using technologies that, if expanded, could effectively complement or even replace microscopic approaches. To date, the scope of such novel technologies is limited and may not include common protozoa such as Dientamoeba fragilis, Entamoeba histolytica, or Cyclospora cayetanensis. This minireview describes canonical approaches for the detection of pathogenic intestinal protozoa, while highlighting recent developments and FDA-approved tools for clinical diagnosis of common intestinal protozoa.

Surveillance for enteric pathogens in a case-control study of acute diarrhea in Western Kenya.

BACKGROUND: Acute diarrhea remains a major public health problem in East African nations such as Kenya. Surveillance for a broad range of enteric pathogens is necessary to accurately predict the frequency of pathogens and potential changes in antibiotic resistance patterns. METHOD: Stool samples were collected from September 2009 to September 2011; 193 and 239 samples, from age-matched cases and asymptomatic controls, were collected, respectively, from Kericho and Kisumu District Hospitals in western Kenya. Bacterial pathogens were identified by conventional microbiological methods; antibiotic susceptibility of bacterial isolates was ascertained using the MicroScan WalkAway 40 Plus. An enzyme immunoassay kit was used to detect rotavirus, and ova and parasite examination was conducted by microscopy and an enzyme immunoassay. RESULTS: Rotavirus (10.2% and 10.5%) and Shigella (11% and 8%) were isolated significantly more often in the cases than the controls from Kericho and Kisumu District Hospitals respectively. The diarrheagenic Escherichia coli, Campylobacter jejuni and Salmonella were found most often in the cases while Giardia lamblia and Entamoeba histolytica/E. dispar were found more often in the controls. Most pathogens were isolated from children under 5 years old. More than 50% of the Shigella, Salmonella and diarrheagenic E. coli isolates were multidrug resistant to ampicillin, tetracycline and trimethoprim/sulfamethoxazole with several enteroaggregative and enterotoxigenic E. coli isolates producing extended-spectrum beta-lactamases. CONCLUSION: Accurate epidemiologic information on acute diarrheal illness in Kenya will be critical for augmenting existing diarrhea management policies in terms of treatment and to strengthen future community awareness and health promotion programs.