Treatment of Bullous Pemphigoid With Dupilumab: A Case Series of 30 Patients.

Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.

An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. These factors make treatment selection challenging and contribute to variable therapeutic response among affected patients. Typical regimens consist of a combination of medical and surgical modalities, tailored to individual responses. However, HS is often refractory to traditional treatments, prompting the need for newer and more effective therapies. Herein, we review current and emerging HS therapies.

Recent Advances in Melanoma Tumorigenesis.

Melanoma is a tumor that continues to increase in both the number of cases presenting and mortality. Patients with disease that has spread beyond the cutaneous boundary still suffer from significant morbidity and mortality despite advances in immune therapy. It is incumbent that clinicians keep up with the latest advances in both tumorigenesis and metastatic capabilities, and be aware of clinical, histopathologic, and genetic metrics to assist in the early diagnosis of aggressive tumors. This review synopsizes some of the most recent findings. J Drugs Dermatol. 2022;21(12):1289-1293. doi:10.36849/JDD.6814.

Modulation of π-stacking modes and photophysical properties of an organic semiconductor through isosteric cocrystallization.

We report on the control of π-stacking modes (herringbone vs slipped-stack) and photophysical properties of 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene (BP4VA), an anthracene-based organic semiconductor (OSC), by isosteric cocrystallization (i.e., the replacement of one functional group in a coformer with another of "similar" electronic structure) with 2,4,6-trihalophenols (3X-ph-OH, where X = Cl, Br, and I). Specifically, BP4VA organizes as slipped-stacks when cocrystallized with 3Cl-ph-OH and 3Br-ph-OH, while cocrystallization with 3I-ph-OH results in a herringbone mode. The photoluminescence and molecular frontier orbital energy levels of BP4VA were effectively modulated by the presence of 3X-ph-OH through cocrystallization. We envisage that the cocrystallization of OSCs with minimal changes in cocrystal formers can provide access to convenient structural and property diversification for advanced single-crystal electronics.

Interactions among the Predatory Midge Aphidoletes aphidimyza (Diptera: Cecidomyiidae), the Fungal Pathogen Metarhizium brunneum (Ascomycota: Hypocreales), and Maize-Infesting Aphids in Greenhouse Mesocosms.

The generalist entomopathogenic fungus, Metarhizium brunneum, has proved to have great potential as a versatile biological pest control agent. The gall midge Aphidoletes aphidimyza is a specialist predator that occurs naturally in Europe and has been successfully used for aphid suppression. However, the interaction between these two biological control organisms and how it may affect the biological control of aphids awaits further investigation. As part of the EU-supported project INBIOSOIL, this study was conducted in greenhouse conditions to assess the possible effects of combining both biological control agents. In a randomized complete block design, sweet corn (Zea mays var. saccharata) plants were grown in large pots filled with natural soil or natural soil inoculated with M. brunneum. At the third leaf stage, before being individually caged, plants were infested with Rhopalosiphum padi and A. aphidimyza pupae were introduced in the soil. Aphidoletes aphidimyza midge emergence, number of living midges and number of aphids were recorded daily. The presence of conidia in the soil and on leaves was assessed during the experiment. At the conclusion of the experiment, the number of live aphids and their developmental stage, consumed aphids, and A. aphidimyza eggs was assessed under stereomicroscope. This study's findings showed that the presence of M. brunneum did not affect A. aphidimyza midge emergence. However, longevity was significantly affected. As the study progressed, significantly fewer predatory midges were found in cages treated with M. brunneum compared to untreated cages. Furthermore, by the end of the study, the number of predatory midges found in the Metarhizium-treated cages was four times lower than in the untreated cages. Both daily and final count of aphids were significantly affected by treatment. Aphidoletes aphidimyza applied alone suppressed the aphid population more effectively than M. brunneum applied alone. Additionally, the aphid population was most suppressed when both agents were combined, though the suppression was less than additive.

Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial.

The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring P. acnes- generated inflammation. P. acnes biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the P. acnes biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the P. acnes biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by P. acnes. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the P. acnes bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

J Drugs Dermatol. 2016;15(6):677-683.

A novel method for automatic treadmill speed adaptation.

Robot-aided treadmill training is an innovative rehabilitation method for patients with locomotor dysfunctions. However, in current rehabilitation systems treadmill speed is restricted to constant values or adjusted by the therapist, whereas self-determined phases of accelerations and decelerations cannot be performed by the patient in an interactive and intuitive way. We present a new approach that allows treadmill walking with intuitive gait speed adaptation. In this approach, the user's trunk position is fixed in walking direction. The horizontal interaction forces applied by the user intending to accelerate or decelerate the gait are measured at the trunk connection and fed to the treadmill controller. The desired gait acceleration is calculated by means of a virtual admittance. Integration yields the desired speed which is fed into the underlying velocity controller of the treadmill. The method was verified by two experimental setups and tested on ten healthy subjects. In one setup, the subject's trunk was rigidly connected by a tether, whereas in the second setup the subject was placed in a robotic gait orthosis. All subjects were able to use both systems immediately and intuitively. The treadmill speed profile during the gait cycle corresponds to that of normal walking. The controller can be extended to simulate different walking conditions, such as slope walking. The method can be used for patient-cooperative control strategies performed with a robotic gait orthosis as well as for any other user-interactive applications in fitness and sports.

A fronto-parietal network is mediating improvement of motor function related to repetitive peripheral magnetic stimulation: A PET-H2O15 study.

Repetitive peripheral magnetic stimulation (RPMS) is a focused and painless stimulation method, in which muscle contractions are elicited by depolarization of the terminal motor branches. Clinical-experimental investigations on different disorders of sensorimotor integration in the last decade have shown that RPMS can be used for the rehabilitation of motor functions after stroke. It is supposed that this therapeutic effect is based on the RPMS-induced proprioceptive inflow to the CNS. To analyze the conditioning effects of RPMS on reorganization of the motor system on cortical level positron emission tomography (PET) is used. Regional cerebral blood flow (rCBF) has been measured using H(2)O(15)-PET in eight patients with arm paresis following focal cerebral ischemic infarction before and after treatment using RPMS on upper arm flexor muscles. Behavioral measures showed a significant improvement of kinematics of finger movements and a reduction of spasticity in the affected arm following RPMS treatment. The recovery was associated with significant increase of neural activation within the superior posterior parietal lobe and the premotor cortex (PM) areas. The increase of activation of the parieto-premotor network following RPMS treatment indicates a significant conditioning effect of RPMS on the cortical level. These results emphasize the positive therapeutic effect of RPMS and describe the physiological bases of its function on the central level.

Neural observer based spasticity quantification during therapeutic muscle stimulation.

Repetitive peripheral magnetic stimulation (RPMS) is an innovative approach in treatment of central paresis, e.g. after stroke. The main goals of our current research are the improvement of the therapeutic effect by inducing closed loop controlled movements on the one hand, and the objective assessment of the RPMS therapy on the other hand. One important parameter that allows the evaluation of the therapy progress and that gives insight in neurological processes is the level of spasticity. Current methods to evaluate spasticity are not completely objective and error-prone. This paper presents a novel method of spasticity quantification. The used algorithms are based on parameter estimation methods and can be executed during the therapeutic stimulation. Hence, objective spasticity parameters can be obtained without applying any extra equipment. The presented method has been tested with one patient.

The JoyntStick: a new force-input-device for a multi-modal desktop simulator.

This paper presents a new force-torque input device that can be used to navigate within any kind of anatomical atlas. As an example, we demonstrate how it can be used to drive a virtual knee joint. The device is comprised by a realistic phantom shank that is attached to a self-made high-sensitive force-torque sensor. It records forces and moments in six degrees-of-freedom and feeds them into a biomechanical model of the knee. Resulting joint movements and sounds are displayed by a visual and acoustic display, respectively. The entire multi-modal simulation environment can provide a better understanding of joint anatomy, e.g. for the education of medical students. Furthermore, it can be a practical tool for resident orthopaedic physicians in order to enhance the consultation, clarification, and treatment planning together with the patient.