[Stable disease or complete response? : A critical evaluation of the radiologic response to immune checkpoint blockade in advanced melanoma]. / Stabile Erkrankung oder vollständiges Ansprechen? : Evaluation der radiologischen Interpretation des Therapieansprechens auf Immune-Checkpoint-Blockade im metastasierten malignen Melanom.

BACKGROUND: Rating the response of melanoma to immune checkpoint blockade (ICB) by conventional CT proves to be difficult, since response patterns and kinetics differ from the classical responses seen with other therapies. Hence, immune-related response criteria were developed. However, they are mainly based on the alteration of the diameter of lesions over time but do not include metabolic activity. OBJECTIVE: The aim of this study was to search for additional criteria to improve the interpretation of the radiologic images of patients with metastatic melanoma after ICB. MATERIALS AND METHODS: We retrospectively analysed 7 patients with metastatic melanoma over a period of 13-41 months after treatment with ICB using contrast enhanced CT scans from the neck region to the lower abdomen and compared the results in the follow ups with 18F-FDG PET/CT. RESULTS: Metastatic lesions in 5 of 7 patients rated as stable disease (SD) in CT staging showed no metabolic activity in 18F-FDG PET/CT. The size of these lesions did not increase or show metabolic activity in the further follow-up, even after discontinuation of ICB. In contrast, tumor lesions in the other 2 patients rated as SD in CT staging showed metabolic activity in 18F-FDG PET/CT. These tumor lesions expanded significantly in the further course of the disease. CONCLUSION: In addition to the size of a tumor lesion, its metabolic activity adds important information regarding treatment response. Thus, we propose that the metabolic activity assessed with 18F-FDG-PET/CT should be included in the immune response criteria. No FDG uptake in a lesion should be rated as inactive tumor rather than SD and further treatment may not be required.

Morphologic features of basal cell carcinoma using the en-face mode in frequency domain optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has become a valuable non-invasive tool in the in vivo diagnosis of non-melanoma skin cancer, especially of basal cell carcinoma (BCC). Due to an updated software-supported algorithm, a new en-face mode - similar to the horizontal en-face mode in high-definition OCT and reflectance confocal microscopy - surface-parallel imaging is possible which, in combination with the established slice mode of frequency domain (FD-)OCT, may offer additional information in the diagnosis of BCC. OBJECTIVES: To define characteristic morphologic features of BCC using the new en-face mode in addition to the conventional cross-sectional imaging mode for three-dimensional imaging of BCC in FD-OCT. METHODS: A total of 33 BCC were examined preoperatively by imaging in en-face mode as well as cross-sectional mode in FD-OCT. Characteristic features were evaluated and correlated with histopathology findings. RESULTS: Features established in the cross-sectional imaging mode as well as additional features were present in the en-face mode of FD-OCT: lobulated structures (100%), dark peritumoral rim (75%), bright peritumoral stroma (96%), branching vessels (90%), compressed fibrous bundles between lobulated nests ('star shaped') (78%), and intranodular small bright dots (51%). These features were also evaluated according to the histopathological subtype. In the en-face mode, the lobulated structures with compressed fibrous bundles of the BCC were more distinct than in the slice mode. CONCLUSION: FD-OCT with a new depiction for horizontal and vertical imaging modes offers additional information in the diagnosis of BCC, especially in nodular BCC, and enhances the possibility of the evaluation of morphologic tumour features.

Comparison of Two Kinds of Lasers in the Treatment of Acne Scars.

Acne scars are common and stigmatizing for the affected patients. Besides surgery, chemical peels, microdermabrasion, and microneedling, the treatment with fractional laser is a standard therapy. The results of reducing acne scars treated either with a fractional Er:YAG (erbium-doped yttrium-aluminum-garnet [Er:Y3Al5O1]) or a carbon dioxide (CO 2 ) laser at different wavelengths were compared and evaluated in the pilot study presented here. Fourteen patients with severe scars on both cheeks were treated four times in a random split-face approach: on one side with Er:YAG laser and on the contralateral side with CO2 laser following a standardized protocol. Therapeutic success was evaluated through the use of a high-resolution, 3D small-field capture system (PRIMOS), digital photography, and the Patient and Observer Scar Assessment Scale (POSAS) questionnaire. The evaluation was performed by a blinded investigator. Treatment results displayed a higher efficacy of the fractional CO2 laser compared with the Er:YAG laser as displayed by digital photographs. Additionally, objective (high-resolution, 3D small-field capture; PRIMOS) and subjective (POSAS) measuring results correlated positively in certain qualities (color, stiffness, thickness, surface, overall opinion). Using a novel scientific approach, we evaluated the therapeutic efficacy of different fractional lasers on acne scars using a rater-blinded approach. Compared with an Er:YAG laser, better skin smoothening was achieved by fractional CO2 laser treatment.

Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.

BACKGROUND: Folliculitis decalvans leads to scarring alopecia through inflammatory destruction of the hair follicle. Currently, antibiotics are most commonly used to treat this disease. However, treatment regimens with antibiotics feature a high relapse rate and encourage the development of resistant bacteria. OBJECTIVE: To evaluate the outcome of different treatment options for folliculitis decalvans. METHODS: Retrospective study to compare the efficacy of different treatment regimens in 28 patients with folliculitis decalvans. RESULTS: The success of treatment with clindamycin and rifampicin, clarithromycin, dapsone and isotretinoin was analysed. The evaluation of the combination of clindamycin and rifampicin showed the lowest success rate in achieving long-term remission, since 80% of the patients relapsed shortly after end of treatment. Clarithromycin and dapsone were more successful with long-term and stable remission rates of 33% and 43% respectively. Treatment with isotretinoin was the most successful oral treatment in our analysis with 90% of the patients experiencing stable remission during and up to two years after cessation of the treatment. CONCLUSION: The common use of antibiotics as first-line therapy in folliculitis decalvans needs to be re-evaluated critically and oral isotretinoin should be considered as valid treatment alternative.

[Dermatitis herpetiformis. An update of the pathogenesis]. / Dermatitis herpetiformis. Aktuelle Aspekte der Pathogenese.

The multifactorial pathogenesis of dermatitis herpetiformis is reviewed in light of current experimental data. Genetic background, gluten consumption, and abnormal immune and autoimmune reactions are the most important pathogenetic factors, but other agents also participate in the disease development. The predisposing and inducing factors are summarized, while the pathophysiological steps leading to the development of skin symptoms are detailed.

5-HT1A receptor-effector system responsivity in panic disorder.

To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic, neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor agonist ipsapirone (IPS) were investigated in patients with primary PD and healthy controls. Fourteen patients and matched controls received a single oral dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but had only minimal effects on behavior. Compared with controls, the patients with PD exhibited significantly attenuated thermoregulatory and neuroendocrine responses to IPS. Although the healthy subjects reported increased drowsiness and the PD patients rated themselves more nervous and less calm following administration of IPS, no consistent changes in ratings of anxiety or panic symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses following 5-HT1A receptor activation reflects subsensitivity of both the pre- and post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex function in conjunction with assessment of the responsivity of other subtypes (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in anxiety disorders and its involvement in anxiolytic drug effects.

5-Hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder. Comparison of patients and controls.

To evaluate 5-hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder, we examined hypothermic, neuroendocrine, and behavioral responses to the selective 5-hydroxytryptamine1A receptor ligand ipsapirone in patients with primary obsessive-compulsive disorder and healthy controls. Twelve patients and 22 controls received a single dose of ipsapirone, 0.3 mg/kg, or placebo under double-blind, random assignment conditions. Ipsapirone induced hypothermia and release of corticotropin and cortisol but had no effect on behavior, including obsessive or compulsive symptoms. Thermoregulatory and neuroendocrine responses to ipsapirone were not consistently different between healthy controls and patients with obsessive-compulsive disorder. These results provide no direct support for the hypothesis that a serotonergic dysfunction related to 5-hydroxytryptamine1A receptors may be linked to the pathophysiologic characteristics of obsessive-compulsive disorder and point to the need for the evaluation of other 5-hydroxytryptamine receptor subtypes. Future studies of the responsivity of 5-hydroxytryptamine1A receptors to direct-acting ligands, such as ipsapirone, should facilitate assessment of the integrity of the 5-hydroxytryptamine system and its involvement in antiobsessional drug effects.

5-HT1A receptor responsivity in unipolar depression. Evaluation of ipsapirone-induced ACTH and cortisol secretion in patients and controls.

The selective 5-HT1A receptor ligand ipsapirone (IPS) induces corticotropin (ACTH) and cortisol secretion in humans. To explore 5-HT1A receptor-mediated hypothalamic-pituitary-adrenal (HPA) system activation in depression, 24 subjects (12 patients with unipolar depression and 12 individually matched controls) were given 0.3 mg/kg IPS or placebo in random order. Compared with controls, the depressed patients exhibited significantly decreased ACTH and cortisol responses to IPS in association with increased basal cortisol secretion. The impaired HPA response following 5-HT1A receptor challenge in unipolar depression could have resulted from glucocorticoid-dependent subsensitivity of the (post-synaptic) 5-HT1A receptor itself and/or from a defective postreceptor signaling pathway [inhibitory guanine nucleotide-binding protein (Gi)-adenylate cyclase complex function], thus supporting the hypothesis that a disintegrated 5-HT and HPA system interaction may be present in depression. Future studies of the HPA response to direct-acting 5-HT1A ligands, such as IPS, should facilitate the assessment of 5-HT/HPA system integrity in various affective disorders and its involvement in psychotropic drug effects.

5-HT1A receptor function in depression: effect of chronic amitriptyline treatment.

Hypothermic responses to 5-HT1A receptor activation by the selective ligand ipsapirone (IPS) were attenuated in depressed patients as compared to controls. Chronic treatment with amitriptyline (AMI) further impaired 5-HT1A-mediated hypothermia. The results indicate a subsensitive (presynaptic) 5-HT1A receptor and/or a defective post-receptor signalling pathway in depression and are consistent with the hypothesis that 5-HT1A receptors are down-regulated during AMI treatment.

Subsensitivity of the 5-hydroxytryptamine1A (5-HT1A) receptor-mediated hypothermic response to ipsapirone in unipolar depression.

The selective 5-HT1A receptor ligand ipsapirone (IPS) induces hypothermia in humans. To explore 5-HT1A receptor-mediated thermoregulation in depression, 24 subjects (12 patients with unipolar depression and 12 individually matched controls) received 0.3 mg/kg IPS or placebo in random order. Compared with controls, the depressed patients exhibited significantly attenuated hypothermic responses to IPS. The impaired hypothermic response following 5-HT1A receptor activation in unipolar depression could have resulted from subsensitivity of the (presynaptic) 5-HT1A receptor and/or related effector mechanisms, thus supporting the hypothesis that altered serotonergic activity may be present in affective disorders. Future studies of the hypothermic response to direct-acting 5-HT1A ligands, such as IPS should facilitate the assessment of 5-HT receptor function in various affective disorders and its involvement in psychotropic drug effects.

An autoradiographic study of the subcortical projections of the rabbit striate cortex in the adult and during postnatal development.

The subcortical projections of the rabbit striate cortex were studied by autoradiography. Small injections of 3H-leucine were placed into the striate cortex of 15 rabbit pups aged between one day and one month and six adult rabbits (strain Chbb:Ch). Terminal fields of projection occurred only ipsilateral to the injection, and these were found in the caudate nucleus (CN), the claustrum (Cla), the thalamic reticular nucleus (TRN), the dorsal (LGNd) and the ventral (LGNv) lateral geniculate nuclei, the pulvinar (Pul), the ventrolateral (Vl) the posterior (Po) thalamic nuclei, the anterior (APN) and posterior (PPN) pretectal nuclei, the nucleus of the optic tract (NOT), the superior colliculus (SC) and the basal pontine nuclei (PN). Cla was innervated via the superficial corticocortical and CN via the corticocaudate pathways. The remaining projections were innervated via the subcortical pathway which comprised three bundles: The deep bundle (to TRN, LGNd, Pul and Po), the superficial bundle (to LGNv, APN, PPN, NOT, and SC), and the peduncular bundle (to PN). The projection to SC showed remarkable changes of its terminal pattern during the first and second postnatal weeks. These changes were characterized by a strong reduction of the horizontal extension of the terminal labelling and an increasing concentration on the stratum griseum superficiale. Similar changes were not observed in the other projections.