Integrating 40-GEP Testing to Improve Clinical Recommendations for Adjuvant Radiation for Cutaneous Squamous Cell Carcinoma: Multidisciplinary Consensus Guidelines.

Early identification and intervention in patients with cutaneous squamous cell carcinoma (cSCC) who are at high risk for metastasis is important for optimal outcomes. Prognostic tools (e.g., American Joint Committee on Cancer, 8th edition [AJCC-8]) and management guidelines (National Comprehensive Cancer Network® [NCCN]) are useful in helping to identify high-risk patients with cSCC who might benefit from adjuvant therapies, such as radiation and/or immunotherapies; however, traditional staging and management guidelines rely on clinicopathologic risk factors to predict risk, which limits their prognostic accuracy. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help clinicians stratify risk in patients with cSCC. The validated 40-GEP test can accurately classify patients with at least one high-risk feature as being at low (Class 1), higher (Class 2A), or highest (Class 2B) biological risk of nodal or distant metastasis within three years of diagnosis. A multidisciplinary panel comprising radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in cSCC management convened in June 2023 to discuss the utility of 40-GEP testing in cSCC clinical decision-making in regard to adjuvant radiation therapy (ART). The panel identified gaps in clinical practice in which 40-GEP testing has particular utility: in escalation of care for lower-stage patients with high-risk tumors; in de-escalation of care for patients for whom the risks of ART may outweigh the benefits; and in decision-making regarding elective radiation to the nodal basin. The expert panel developed a risk-based clinical workflow for ART in patients with cSCC, utilizing 40-GEP testing within NCCN management guidelines and AJCC-8 staging.

Signatures of Exciton Orbits in Quantum Mechanical Recurrence Spectra of Cu_{2}O.

The seminal work by Kazimierczuk et al. [Nature 514, 343 (2014)10.1038/nature13832] has shown the existence of highly excited exciton states in a regime, where the correspondence principle is applicable and quantum mechanics turns into classical mechanics; however, any interpretation of exciton spectra based on a classical approach to excitons is still missing. Here, we close this gap by computing and comparing quantum mechanical and semiclassical recurrence spectra of cuprous oxide. We show that the quantum mechanical recurrence spectra exhibit peaks, which, by application of semiclassical theories and a scaling transformation, can be directly related to classical periodic exciton orbits. The application of semiclassical theories to exciton physics requires the detailed analysis of the classical exciton dynamics, including three-dimensional orbits, which strongly deviate from hydrogenlike Keplerian orbits. Our findings illuminate important aspects of excitons in semiconductors by directly relating the quantum mechanical band structure splittings of excitons to the corresponding classical exciton dynamics.

Structural Determination of an Unusual CuI -Porphyrin-π-Bond in a Hetero-Pacman Cu-Zn-Complex.

The synthesis and characterization of a hetero-dinuclear compound is presented, in which a copper(I) trishistidine type coordination unit is positioned directly above a zinc porphyrin unit. The close distance between the two coordination fragments is secured by a rigid xanthene backbone, and a unique (intramolecular) copper porphyrin-π-bond was determined for the first time in the molecular structure. This structural motif was further analyzed by temperature-dependent NMR studies: In solution at room temperature the coordinative bond fluctuates, while it can be frozen at low temperatures. Preliminary reactivity studies revealed a reduced reactivity of the copper(I) moiety towards dioxygen. The results adumbrate why nature is avoiding metal porphyrin-π-bonds by fixing reactive metal centers in a predetermined distance to each other within multimetallic enzymatic reaction centers.

Facile C=O Bond Splitting of Carbon Dioxide Induced by Metal-Ligand Cooperativity in a Phosphinine Iron(0) Complex.

New iron complexes [Cp*FeL]- (1-σ and 1-π, Cp*=C5 Me5 ) containing the chelating phosphinine ligand 2-(2'-pyridyl)-4,6-diphenylphosphinine (L) have been prepared, and found to undergo facile reaction with CO2 under ambient conditions. The outcome of this reaction depends on the coordination mode of the versatile ligand L. Interaction of CO2 with the isomer 1-π, in which L binds to Fe through the phosphinine moiety in an η5 fashion, leads to the formation of 3-π, in which CO2 has undergone electrophilic addition to the phosphinine group. In contrast, interaction with 1-σ-in which L acts as a σ-chelating [P,N] ligand-leads to product 3-σ in which one C=O bond has been completely broken. Such CO2 cleavage reactions are extremely rare for late 3d metals, and this represents the first such example mediated by a single Fe centre.

Histopathology of Moyamoya angiopathy in a European patient.

BACKGROUND AND PURPOSE: Moyamoya angiopathy (MMA) is rare outside Asia. Little is known about pathophysiology in European patients. This study aims to elucidate the histopathology of non-Asian MMA and its similarities and differences to those cases from Asia. METHODS: Here, we present a 57-year-old European woman with MMA and describe the post-mortem examination results of the brain and cerebral arteries. RESULTS: Histopathological findings in cerebral blood vessels were identical to those found in Asians. This included thickening and undulation of the internal elastic lamina as well as fibrocellular thickening and proliferation of smooth muscle cells of the intima in the distal segments of the internal carotid arteries and in proximal and middle segments of the anterior and middle cerebral arteries. Collateral vessels showed fragmented internal elastic lamina and thinning of the media with isolated microaneurysms. CONCLUSIONS: Histopathological changes found in this European patient are identical with those described in Asians. Despite suspected different genetic triggers and unknown pathophysiological cascades, MMA in Europeans seems to result in a common final pathway compared with the disease in Asians.

Cutaneous malignant melanoma of the oral cavity following skin graft reconstruction: Case report.

BACKGROUND: Malignant melanomas on skin graft recipient sites are rare, with few cases reported in the literature. METHODS: We present a case report of a patient with recurrent cutaneous melanoma in the grafted anterolateral thigh flap of the tongue. RESULTS: A patient underwent hemiglossectomy with free flap reconstruction for squamous cell carcinoma of the tongue. Five years later the patient was seen with a 1-cm nodule and surrounding erythroplakia at the recipient site of the graft. Analysis revealed cutaneous malignant melanoma. Patient then related a remote history of a suspected skin melanoma of the donor leg that had been treated with excision, with unknown histology. CONCLUSION: This may be the first reported case of a cutaneous malignant melanoma in the oral cavity following an anterolateral thigh free flap reconstruction, emphasizing the importance of obtaining a comprehensive history of skin cancers and closely inspecting the donor site prior to graft harvesting.

Utility of 3-Month Surveillance F-18 FDG PET/CT in Surgically Resected Oral Squamous Cell Carcinoma.

OBJECTIVES: To evaluate the performance of surveillance F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) 1 year after imaging in oral squamous cell carcinoma (OSCC) patients treated with definitive surgery and adjuvant (chemo)radiotherapy (RT). METHODS AND MATERIALS: Surveillance PET/CT accuracy was retrospectively evaluated in OSCC patients receiving surgical resection and (chemo)RT. Pathologic risk factors were assessed for influence on accuracy of the post-RT PET/CT. RESULTS: Fifty-four patients with median follow-up of 3.8 years met inclusion criteria. A PET/CT obtained a median of 3.4 months after RT revealed 11 (20.4%) instances of true disease recurrence: 4 locoregional alone, 6 distant alone, and 1 patient with locoregional and distant disease. Locoregional detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 55.6%, 75.0%, 33.3%, and 88.2%, respectively. For distant recurrence, the respective values were 100%, 95.2%, 77.8%, and 100%. Absence of bone invasion, absence of pT4 disease, and disease within the tongue were independently associated with higher sensitivity ( P = .048). Perineural invasion was associated with increased specificity ( P = .027), and tumor location in the tongue was associated with a higher PPV ( P = .007) on surveillance PET/CT. CONCLUSIONS: Post-RT PET/CT accuracy information for surgically managed OSCC patients demonstrates significant associations with pathologic factors.

Mental contrasting with implementation intentions (MCII) improves physical activity and weight loss among stroke survivors over one year.

OBJECTIVE: Stroke is the most common cause of physical impairment, and having already had a stroke dramatically increases the risk of having another one. Although greater physical activity lowers rates of stroke recurrence, patients often fail to act in line with this recommendation. The present intervention tested whether teaching the self-regulation strategy of mental contrasting (MC) with implementation intentions (II; MCII) improves stroke patients' physical activity and weight loss over 1 year compared with 2 information-only, control interventions. RESEARCH METHOD: Participants were 183 stroke survivors who were capable of adhering to physical activity recommendations (age: M = 57 years; body mass index (BMI): M = 30). Patients were randomized to 3 conditions: unstructured information (n = 61), structured information (n = 62), and structured information plus MCII (n = 60). Patients' physical activity was assessed 50 weeks after they had left the rehabilitation hospital using the Baecke Inventory (Baecke, Burema, & Frijters, 1982), and by diaries provided at 2 consecutive weekends after 0, 10, 20, 30, 40, and 50 weeks. Diaries were also used to assess weight change. RESULTS: MCII participants were more physically active after the 50 weeks (Baecke Inventory: 2.74 vs. 2.59, p < .05; diary: 62.45 vs. 54.11, p = .03) and lost more weight (2.15 kg, p = .02) compared with participants in the control conditions. CONCLUSIONS: Teaching the MCII self-regulation strategy enhanced long-term physical activity in stroke patients relative to health information on its own. MCII thus qualifies as an effective intervention technique to improve secondary stroke prevention. (PsycINFO Database Record

Making if-then plans counteracts learned non-use in stroke patients: A proof-of-principle study.

BACKGROUND: After stroke, the learned non-use of a paretic arm is a major obstacle to the improvement of hand function. OBJECTIVE: We examined whether patients with a central paresis could profit from applying the self-regulation strategy of making if-then plans that specify situational triggers to using the paretic arm. METHOD: Seventeen stroke patients with a mild to moderate hand paresis were asked to perform a Simon task which is commonly used to study the enhanced executive control needed when there is a mismatch between stimulus (e.g., color) and response (e.g., location) features. We examined whether patients with hemiparesis would be able to reduce the Simon effect (i.e., responding slower to mismatched as compared to matched stimulus and response features) by creating new stimulus-response associations via if-then plans. RESULTS: A significant Simon effect was observed in both the affected and the non-affected arm for control trials. However, there was no longer a significant Simon effect for the critical trials prepared by forming if-then plans. This led to a significant stimulus×compatibility interaction effect for the affected arm and a marginally significant interaction effect for the non-affected arm. Making if-then plans was effective for eliminating or at least reducing the Simon effect for the affected and the non-affected arm, respectively. CONCLUSION: This observation opens a potential new route to improving stroke rehabilitation. If-then plans may qualify as a viable strategy to overcome the learned non-use of the affected arm. Further research is now required to develop and test therapeutic measures based on this proof-of-principle.

[Psychotherapy and Religion: A Representative Survey Among Psychotherapists in Southern Germany]. / Psychotherapie und Religion: Eine repräsentative Umfrage unter Psychotherapeuten in Süddeutschland.

Objective: Religion and spirituality play an appreciable role as a problem area or as a resource for patients with mental disorders. It is therefore of interest what attitudes psychotherapists assume towards this complex range of issues in their work, but also in their personal lives. The majority of empirical studies on this subject originate from the USA, with little data being available from Europe and Germany. Our own survey among practising psychotherapists was designed to elucidate these questions. Method and Study Population: A cross-sectional study was conducted in the form of a written survey of all accessible practising psychotherapists in the area of Northern Bavaria (Franconian administrative districts; n=1 081, return rate 65%). Results: Around two-thirds of the therapists consider religion to be an important subject in psychotherapy, but only one-fifth of them routinely take a history of the patients' religious beliefs. The therapists' own closeness to religion correlates positively with the tendency to incorporate religion in their therapy. In around one-third of the therapists, religion holds an important place within their own world view, although significantly fewer psychotherapists than the general population of Franconia are bound to a specific confession. Around one-quarter had at least once consulted a pastor due to a patient, while each seventh therapist had at least once actively mediated contact to a pastor. Conclusions: Religion is a subject that is relevant for therapeutic practice, but a history of religious beliefs is rarely taken on a routine basis. The incorporation of religion into psychotherapy correlates with religious characteristics of the therapists ("personal bias"). There appears to be a "religiosity gap" between psychotherapists and the general population. Advanced training on the subject of "religion/spirituality" and increased consideration in supervision may counteract the danger of religious needs and religion-related resources of patients being neglected.

Change of maximum standardized uptake value slope in dynamic triphasic [18F]-fluorodeoxyglucose positron emission tomography/computed tomography distinguishes malignancy from postradiation inflammation in head-and-neck squamous cell carcinoma: a prospective trial.

PURPOSE: To evaluate dynamic [(18)F]-fluorodeoxyglucose (FDG) uptake methodology as a post-radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG-positron emission tomography/computed tomography (FDG-PET/CT). METHODS AND MATERIALS: We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV(max)) of regions of interest were measured at 60, 90, and 120 minutes. The SUV(max) slope between 60 and 120 minutes and change of SUV(max) slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up. RESULTS: A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV(max) slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV(max) ≥2.5 (P=.02). CONCLUSIONS: The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV(max) slope, accurately distinguishing tumor from inflammation on positive and equivocal scans.

Implementation of a diabetes management program for patients in a rural primary care office.

OBJECTIVE: A diabetes management program was implemented in a rural primary care office for those who did not choose to consult a multidisciplinary specialty care. The purposes of this study were to describe the current practices and health care provider management of patients with diabetes in a rural primary care office and determine differences between Hispanic and non-Hispanic persons concerning diabetes self-care behaviors, barriers to self-care, and their association with glycosylated hemoglobin level. METHODS: A retrospective medical record review of diabetes-related medical information was completed. RESULTS: Sixty-one (74%) of the 83 patients with diabetes completed the questionnaire and had the diabetes management program implemented (problem summary and clinical summary generated). Medical record review was completed for 83 (100%) subjects. Glycosylated hemoglobin was significantly higher for the younger group and women. Hispanic women and married persons had significantly higher glycosylated hemoglobin than did non-Hispanic and unmarried persons. Hispanic persons who were obese had significantly higher glycosylated hemoglobin. Self-care behaviors for managing diabetes were different by group. Non-Hispanic subjects reported taking their diabetes medications 99% of the time and Hispanic subjects 50% of the time. DISCUSSION: It was feasible to implement a diabetes management program in a rural primary care setting, and its implementation highlighted the ethnic differences for Hispanics and non-Hispanics in diabetes self-care behavior, barriers to self-care, and family support for diabetes management. The implementation of the diabetes management program, though, was time-consuming and costly and was facilitated outside of the usual realm of practice.

Continuous interscalene analgesia with ropivacaine 0.2% versus ropivacaine 0.3% after open rotator cuff repair: the effects on postoperative analgesia and motor function.

BACKGROUND: Interscalene analgesia is a recognized technique for the management of postoperative pain after major shoulder surgery. The most effective local anesthetic concentration in this setting is still controversial. In this study, we compared the analgesia and side effects of a continuous infusion of ropivacaine 0.2% and 0.3% administered through an interscalene catheter for the first 48 hours after surgery. METHODS: Eighty consecutive patients scheduled for elective open rotator cuff repair were randomized into 2 groups to receive a continuous infusion of either ropivacaine 0.2% or ropivacaine 0.3% for 48 hours at a rate of 14 mL/h through an interscalene catheter after a preoperative bolus of 40 mL ropivacaine 0.5% in all patients. Pain score (visual analog scale 0-100), intensity of motor block, quality of sleep during the first postoperative night, morphine consumption, side effects, and patient satisfaction were assessed by an anesthesiologist masked to treatment group. RESULTS: Total morphine consumption was significantly reduced in group 0.3% (12 vs 30 mg). Quality of sleep was significantly better in group 0.3% (4% vs 27% of awakening during the first postoperative night). Handgrip strength, visual analog scale scores, and side effects were similar in both groups. CONCLUSION: The use of ropivacaine 0.3% through an interscalene catheter for the first 48 hours after open rotator cuff repair provided a significant reduction of morphine consumption and a better sleep quality for the first postoperative night without increasing the intensity of motor block or side effects.

Postoperative intravenous morphine consumption, pain scores, and side effects with perioperative oral controlled-release oxycodone after lumbar discectomy.

BACKGROUND: Oral opioid formulations contribute to postoperative analgesia. In this study, we evaluated the perioperative application of oral controlled-release oxycodone to reduce postoperative IV morphine consumption and opioid side effects after lumbar discectomy. METHODS: Forty patients scheduled for elective lumbar discectomy over 1 or 2 levels were included in this prospective, randomized, double-blind, placebo-controlled study. Every 12 h patients received either 20 mg oral controlled-release oxycodone or placebo, from the evening before surgery until the second postoperative morning. All patients received IV morphine via a morphine patient-controlled analgesia device for postoperative analgesia. Acetaminophen 1 g was administered to all patients every 6 h. Postoperative IV morphine consumption was assessed separately for T(0)-T(24) and T(24)-T(48). Postoperative assessments were conducted every 6 h for the first 48 h after surgery. Postoperative analgesia assessments included pain at rest, during coughing, and with motion, using a visual analog scale. Nausea, vomiting, pruritus, sedation, and bowel function were also assessed every 6 h. Patients rated their satisfaction with postoperative analgesia 72 h postoperatively. RESULTS: Postoperative IV morphine consumption was significantly reduced during T(0)-T(24) (26 +/- 10 mg vs 52 +/- 29 mg) and T(24)-T(48) (13 +/- 8 mg vs 33 +/- 18 mg) in the controlled-release oxycodone group compared with that in the placebo group. Pain scores at rest, during coughing, and with motion were significantly lower during the first 48 postoperative hours in the controlled-release oxycodone group. Postoperative nausea and vomiting were significantly reduced during the first 24 h in the controlled-release oxycodone group. Lastly, the controlled-release oxycodone group also experienced significantly earlier recovery of bowel function and had higher patient satisfaction with pain therapy. CONCLUSIONS: Perioperative oral controlled-release oxycodone reduces postoperative IV morphine consumption after lumbar discectomy while providing good analgesia with fewer side effects compared with placebo.

The effect of meperidine on thermoregulation in mice: involvement of alpha2-adrenoceptors.

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.