Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. OBJECTIVE: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. METHODS: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). RESULTS: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. CONCLUSIONS: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.

Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials.

Ocrelizumab is a B cell-depleting drug widely used in relapsing-remitting multiple sclerosis (RRMS) and primary-progressive MS. In RRMS, it is becoming increasingly apparent that accumulation of disability not only manifests as relapse-associated worsening (RAW) but also as progression independent of relapse activity (PIRA) throughout the disease course. This study's objective was to investigate the role of PIRA in RRMS patients treated with ocrelizumab. We performed a single-center, retrospective, cross-sectional study of clinical data acquired at a German tertiary multiple sclerosis referral center from 2018 to 2022. All patients with RRMS treated with ocrelizumab for at least six months and complete datasets were analyzed. Confirmed disability accumulation (CDA) was defined as a ≥ 12-week confirmed increase from the previous expanded disability status scale (EDSS) score of ≥ 1.0 if the previous EDSS was ≤ 5.5 or a ≥ 0.5-point increase if the previous EDSS was > 5.5. PIRA was defined as CDA without relapse since the last EDSS measurement and at least for the preceding 12 weeks. RAW was defined as CDA in an interval of EDSS measurements with ≥ 1 relapses. Cox proportional hazard models were used to analyze the probability of developing PIRA depending on various factors, including disease duration, previous disease-modifying treatments (DMTs), and optical coherence tomography-assessed retinal degeneration parameters. 97 patients were included in the analysis. Mean follow-up time was 29 months (range 6 to 51 months). 23.5% developed CDA under ocrelizumab therapy (n = 23). Of those, the majority developed PIRA (87.0% of CDA, n = 20) rather than RAW (13.0% of CDA, n = 3). An exploratory investigation using Cox proportional hazards ratios revealed two possible factors associated with an increased probability of developing PIRA: a shorter disease duration prior to ocrelizumab (p = 0.02) and a lower number of previous DMTs prior to ocrelizumab (p = 0.04). Our data show that in ocrelizumab-treated RRMS patients, the main driver of disability accumulation is PIRA rather than RAW. Furthermore, these real-world data show remarkable consistency with data from phase 3 randomized controlled trials of ocrelizumab in RRMS, which may increase confidence in translating results from tightly controlled RCTs into the real-world clinical setting.

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

Successful desensitization with chemotherapeutic drugs: a tertiary care center experience.

SUMMARY: Introduction.Hypersensitivity reactions to chemotherapeutic drugs are increasing all over the world, and desensitization to them has become the standard treatment approach. This study aimed to evaluate the characteristics of chemotherapeutic drug hypersensitivity reactions and the outcome of desensitization procedures. Methods. Between January 2017 and 2019, patients who have been desensitized to chemotherapeutic drugs were included retrospectively. Data were obtained from the medical records of the patients. Results. A total of 35 patients were evaluated; of whom 24 (68.5%) were female and 11 were male (31.5%). The mean age was 54.54 ± 13.39 (min-max: 41-69) years. Colorectal cancer was the most common malignancy (n:14, 40%). Desensitization was performed with oxaliplatin in 17 (48.5%), carboplatin in nine (25.7%), paclitaxel in four (11.4%), cisplatin in two (5.7%), irinotecan in two (5.7%), rituximab in two (5.7%), and docetaxel in one (2.8%) patients. Thirty four (97.1%) were successfully desensitized without any reactions. Anaphylaxis occurred during desensitization with rituximab and the procedure could not be completed. The reactions occurred during the first administration of the chemotherapeutic agent in five (14.2%) patients. Skin tests were performed on 26 (74.2%) patients. Skin prick and intradermal tests were positive in 7 (26.9%) and 12 (46.1%) patients, respectively. Conclusions. Desensitization is an effective and safe treatment approach for chemotherapeutic drug hypersensitivity and can be performed safely by observing general precautions to anaphylaxis.

Extended p_{3/2} Neutron Orbital and the N=32 Shell Closure in

The one-neutron knockout from ^{52}Ca in inverse kinematics onto a proton target was performed at ∼230 MeV/nucleon combined with prompt γ spectroscopy. Exclusive quasifree scattering cross sections to bound states in ^{51}Ca and the momentum distributions corresponding to the removal of 1f_{7/2} and 2p_{3/2} neutrons were measured. The cross sections, interpreted within the distorted-wave impulse approximation reaction framework, are consistent with a shell closure at the neutron number N=32, found as strong as at N=28 and N=34 in Ca isotopes from the same observables. The analysis of the momentum distributions leads to a difference of the root-mean-square radii of the neutron 1f_{7/2} and 2p_{3/2} orbitals of 0.61(23) fm, in agreement with the modified-shell-model prediction of 0.7 fm suggesting that the large root-mean-square radius of the 2p_{3/2} orbital in neutron-rich Ca isotopes is responsible for the unexpected linear increase of the charge radius with the neutron number.

Pairing Forces Govern Population of Doubly Magic

Direct proton-knockout reactions of ^{55}Sc at ∼220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Isospin Properties of Nuclear Pair Correlations from the Level Structure of the Self-Conjugate Nucleus

The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N=Z) nuclide _{44}^{88}Ru_{44} has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in ^{88}Ru were populated via the ^{54}Fe(^{36}Ar,2nγ)^{88}Ru^{*} fusion-evaporation reaction at the Grand Accélérateur National d'Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to ^{88}Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N>Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N=Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.

Quasifree Neutron Knockout from

Exclusive cross sections and momentum distributions have been measured for quasifree one-neutron knockout reactions from a ^{54}Ca beam striking on a liquid hydrogen target at ∼200 MeV/u. A significantly larger cross section to the p_{3/2} state compared to the f_{5/2} state observed in the excitation of ^{53}Ca provides direct evidence for the nature of the N=34 shell closure. This finding corroborates the arising of a new shell closure in neutron-rich calcium isotopes. The distorted-wave impulse approximation reaction formalism with shell model calculations using the effective GXPF1Bs interaction and ab initio calculations concur our experimental findings. Obtained transverse and parallel momentum distributions demonstrate the sensitivity of quasifree one-neutron knockout in inverse kinematics on a thick liquid hydrogen target with the reaction vertex reconstructed to final state spin-parity assignments.

IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia.

OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and non-cachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50‒80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the inflammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 non-cachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT- PCR analysis. RESULTS: Our findings demonstrated that IL-6 mRNA levels considerably increased 19.89±8.25, 5.18±2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21±11.72 and 8.85±3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p<0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

How Robust is the N=34 Subshell Closure? First Spectroscopy of

The first γ-ray spectroscopy of ^{52}Ar, with the neutron number N=34, was measured using the ^{53}K(p,2p) one-proton removal reaction at ∼210 MeV/u at the RIBF facility. The 2_{1}^{+} excitation energy is found at 1656(18) keV, the highest among the Ar isotopes with N>20. This result is the first experimental signature of the persistence of the N=34 subshell closure beyond ^{54}Ca, i.e., below the magic proton number Z=20. Shell-model calculations with phenomenological and chiral-effective-field-theory interactions both reproduce the measured 2_{1}^{+} systematics of neutron-rich Ar isotopes, and support a N=34 subshell closure in ^{52}Ar.

The impact of O2/Ar ratio on morphology and functional properties in reactive sputtering of metal oxide thin films.

Morphology is a critical parameter for various thin film applications, influencing properties like wetting, catalytic performance and sensing efficiency. In this work, we report on the impact of oxygen partial flow on the morphology of ceramic thin films deposited by pulsed DC reactive magnetron sputtering. The influence of O2/Ar ratio was studied on three different model systems, namely Al2O3, CuO and TiO2. The availability of oxygen during reactive sputtering is a key parameter for a versatile tailoring of thin film morphology over a broad range of nanostructures. TiO2 thin films with high photocatalytic performance (up to 95% conversion in 7 h) were prepared, exhibiting a network of nanoscopic cracks between columnar anatase structures. In contrast, amorphous thin films without such crack networks and with high resiliency to crystallization even up to 950 °C were obtained for Al2O3. Finally, we report on CuO thin films with well aligned crystalline nanocolumns and outstanding gas sensing performance for volatile organic compounds as well as hydrogen gas, showing gas responses up to 35% and fast response in the range of a few seconds.

Vocal fold paralysis due to intracranial hypotension following spinal anesthesia.

Cranial nerve palsy is a rare neurological complication of epidural and subarachnoid blocks. Most of these complications are attributed to secondary intracranial hypotension due to cerebrospinal fluid leakage following dural puncture. Vocal fold paralysis (VFP) seems more likely to be overlooked and underreported due to delayed onset of symptoms and lack of attribution of dysphonia to spinal anesthesia. Therefore, VFP can often be missed and described as idiopathic. This article describes a case of VFP due to vagus nerve injury following subarachnoid block.

[MOG encephalomyelitis: international recommendations on diagnosis and antibody testing]. / MOG-Enzephalomyelitis: Internationale Empfehlungen zu Diagnose und Antikörpertestung.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.

Lifetime Measurements of Excited States in

Lifetimes of the first excited 2^{+} and 4^{+} states in the extremely neutron-deficient nuclide ^{172}Pt have been measured for the first time using the recoil-distance Doppler shift and recoil-decay tagging techniques. An unusually low value of the ratio B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+})=0.55(19) was found, similar to a handful of other such anomalous cases observed in the entire Segré chart. The observation adds to a cluster of a few extremely neutron-deficient nuclides of the heavy transition metals with neutron numbers N≈90-94 featuring the effect. No theoretical model calculations reported to date have been able to explain the anomalously low B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios observed in these cases. Such low values cannot, e.g., be explained within the framework of the geometrical collective model or by algebraic approaches within the interacting boson model framework. It is proposed that the group of B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios in the extremely neutron-deficient even-even W, Os, and Pt nuclei around neutron numbers N≈90-94 reveal a quantum phase transition from a seniority-conserving structure to a collective regime as a function of neutron number. Although a system governed by seniority symmetry is the only theoretical framework for which such an effect may naturally occur, the phenomenon is highly unexpected for these nuclei that are not situated near closed shells.

[Diagnosis of multiple sclerosis: revision of the McDonald criteria 2017]. / Diagnose der Multiplen Sklerose: Revision der McDonald-Kriterien 2017.

Multiple sclerosis (MS) is the most common chronic autoimmune disorder of the central nervous system (CNS) largely affecting young adults. The diagnosis of MS is based on two pillars: 1) detection of the spatial and temporal dissemination of focal neurological deficits and 2) exclusion of important differential diagnoses. The current revision of the diagnostic criteria (McDonald 2017) also follows these principles, takes new data on magnetic resonance imaging (MRI) into account and reintroduces the role of cerebrospinal fluid (CSF) diagnostics for relapsing-remitting forms. The main priority is a reliable diagnosis as early as possible with the aim of a timely initiation of course-adapted treatment. Some of the concrete innovations are the consideration of cortical MRI lesions (equivalent to juxtacortical foci), the elimination of a distinction between asymptomatic and symptomatic MRI lesions and consideration of characteristic CSF findings for the criterion of temporal dissemination. Relapsing MS can be diagnosed at the time of the first attack by the detection of CSF-specific oligoclonal bands and the MRI detection of a typical local lesion distribution (even without simultaneous detection of a contrast-enhancing lesion). For the primary progressive course, for which a first treatment option has recently been approved, the known definition remains unaltered. With respect to the differential diagnosis there is a clear demarcation from Devic's syndrome, now known as neuromyelitis optica spectrum disorders (NMOSD), as recent insights indicate a separate disease entity caused by an autoimmune response against the astrocytic aquaporin 4 (AQP4) water channel. Finally, future studies will have to provide a definition for secondary progressive MS courses and clarify how to handle diseases characterized by antibodies against myelin oligodendrocyte glycoprotein (MOG) or patients with radiologically isolated syndrome (RIS), i. e. incidental MRI-based detection of CNS lesions in the absence of any clinical event. In summary, McDonald 2017 is within the conceptual structure of its predecessor and simplifies an early diagnosis, thus paving the way to early treatment of MS.

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing.

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.

[Cladribine tablets : Oral immunotherapy of relapsing-remitting multiple sclerosis with short yearly treatment periods]. / Cladribin-Tabletten : Orale Immuntherapie der schubförmigen Multiplen Sklerose mit kurzen, jährlichen Behandlungsphasen.

BACKGROUND: The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS). OBJECTIVE: Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice. RESULTS: Cladribine tablets are administered during two treatment phases of 8-10 (two times 4-5) days with a 1-year interval. The drug selectively reduces the number of T and B lymphocytes, which are subsequently gradually reconstituted with divergent kinetics. A pronounced and sustained effect on the clinical and paraclinical MS disease activity is achieved with good tolerability and a favorable overall safety profile. After completing the two short treatment phases, a relevant proportion of the treated patients experience a prolonged treatment-free period with absence of relevant disease activity. Regular monitoring of lymphocyte counts and reliable contraception during the required time frames are the most important safety measures. There is no evidence of an increased risk of malignancies. CONCLUSION: Cladribine tablets are an important addition to the therapeutic landscape in RMS. With patient-friendly short dosing periods and a favorable adverse event profile, cladribine tablets provide a sustained and strong reduction of MS disease activity. The primary target population for cladribine tablets is patients with relevant MS disease activity (highly active RMS) while on first-line treatment, e. g. with injectable disease-modifying drugs.

Self-organized nanocrack networks: a pathway to enlarge catalytic surface area in sputtered ceramic thin films, showcased for photocatalytic TiO2.

Sputter deposited photocatalytic thin films offer high adherence and mechanical stability, but typically are outperformed in their photocatalytic properties by colloidal TiO2 nanostructures, which in turn typically suffer from problematic removal. Here we report on thermally controlled nanocrack formation as a feasible and batch applicable approach to enhance the photocatalytic performance of well adhering, reactively sputtered TiO2 thin films. Networks of nanoscopic cracks were induced into tailored columnar TiO2 thin films by thermal annealing. These deep trenches are separating small bundles of TiO2 columns, adding their flanks to the overall catalytically active surface area. The variation of thin film thickness reveals a critical layer thickness for initial nanocrack network formation, which was found to be about 400 nm in case of TiO2. The columnar morphology of the as deposited TiO2 layer with weak bonds between respective columns and with strong bonds to the substrate is of crucial importance for the formation of nanocrack networks. A beneficial effect of nanocracking on the photocatalytic performance was experimentally observed. It was correlated by a simple geometric model for explaining the positive impact of the crack induced enlargement of active surface area on photocatalytic efficiency. The presented method of nanocrack network formation is principally not limited to TiO2 and is therefore seen as a promising candidate for utilizing increased surface area by controlled crack formation in ceramic thin films in general.

Extreme tuning of wetting on 1D nanostructures: from a superhydrophilic to a perfect hydrophobic surface.

The tuning of wetting over an extreme range, from superhydrophilic to superhydrophobic, was demonstrated on 1D Al/Al2O3 nanostructures. While chaotic and tangled 1D Al/Al2O3 nanostructures exhibited complete wetting, they became water repellent (with a water contact angle (CA) ≥173°) after the infiltration of poly[bis(2,2,2-trifluoroethoxy)phosphazene] (PTFEP) solution. This simple strategy allows the achievement of two extreme wetting regimes, perfect wetting and non-wetting, without altering the nanostructured surface topography. The same surface was also found to exhibit repellency towards artificial blood and hexadecane.