Comparative Effectiveness of Tofacitinib and Adalimumab in Axial Spondyloarthritis: A Real-World Clinical Context Multicenter Study.

INTRODUCTION: Tofacitinib, an oral Janus kinase inhibitor, is a putative choice in the treatment of axial spondyloarthritis (AxSpA). The objective of this study was to compare the effectiveness and tolerability of tofacitinib with adalimumab, in AxSpA, in a real-world clinical setting. METHODS: In this multicentric medical records review study, adult patients with active AxSpA treated with either tofacitinib 5 mg twice daily or adalimumab 40 mg subcutaneously fortnightly were recruited. Effectiveness was measured with Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Drug-cost analysis was calculated with Incremental Cost-Effectiveness Ratio (ICER drug ). RESULTS: Among the 266 patients, 135 were treated with tofacitinib and 131 with adalimumab (follow-up: 6.5 ± 1.6 months). Mean improvement of BASDAI (3.39 ± 0.09 vs. 3.14 ± 1.16, respectively) and that of ASDAS (1.78 ± 0.68 vs. 2.07 ± 2.08, respectively) were comparable between the adalimumab and tofacitinib groups. A higher proportion of patients achieved BASDAI50 response in the second (49.5% vs. 31.6%) and fourth month (83.9% vs. 62.8%) and ASDAS low disease activity in the fourth month (71.6% vs. 47.9%) in the adalimumab group. All disease activity measurements were similar by the sixth month in both groups. A higher proportion of patients in the tofacitinib group than in the adalimumab group required change in therapy (14.8% vs. 7.6%, respectively). ICER drug for adalimumab compared with tofacitinib was US $188.8 per patient in the adalimumab group for each person-month with BASDAI <4. CONCLUSIONS: Tofacitinib showed comparable effectiveness with adalimumab in patients with AxSpA at the sixth month, despite lesser response in the initial months, with favorable ICER drug .

Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39 years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5 months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12 months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13 months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

A case of central nervous system vasculitis secondary to rheumatoid arthritis treated successfully with mycophenolate.

Here, we report a case of central nervous system vasculitis in rheumatoid arthritis (RA) treated successfully with corticosteroid and mycophenolate. A 53-year-old female with poorly controlled RA presented with unilateral lower motor neurone type seventh cranial nerve palsy. Magnetic resonance imaging (MRI) of the brain revealed bilateral signal intensity changes in posterior fossa, basal ganglia, and periventricular white matter with contrast enhancement. Rheumatoid factor, anti-cyclic citrullinated peptides, and C-reactive protein were high. Cerebrospinal fluid analysis showed pleocytosis with elevated protein. Digital subtraction angiography of the brain revealed a beading pattern in distal branches of anterior, middle, and posterior cerebral arteries bilaterally suggestive of central nervous system vasculitis. We treated the patient with intravenous methylprednisolone followed by oral prednisolone tapered off in 6 months. Mycophenolate mofetil was started at the dose of 2 g per day, along with prednisolone. Sulfasalazine and hydroxychloroquine were also started to treat her arthritis. The patient showed complete neurological improvement, along with a significant resolution of the lesions in MRI.

Efficacy of leflunomide as a steroid-sparing agent in treatment of Indian giant cell arteritis patients: A 2-year follow-up study.

OBJECTIVES: To evaluate the effectiveness of leflunomide as a steroid-sparing agent among Indian patients with giant cell arteritis (GCA) and to assess the changes of "halo sign" within affected arteries, detected ultrasonographically, after remission. METHODS: In this prospective observational study, patients fulfilling American College of Rheumatology criteria for GCA and having halo sign in temporal artery ultrasound were treated with leflunomide and predefined tapering dose of prednisolone. Ultrasounds of temporal and axillary arteries were done at baseline and after remission were achieved. RESULTS: Twenty-two GCA patients were followed up for a median duration of 24 months (interquartile range, IQR: 18-33). All patients showed clinical improvement and steroids could be stopped in 17 out of 22 patients. Median time to achieve remission (symptom-free with normal inflammatory markers) was 3 (95% confidence interval [CI]: 2.4-3.6) months. Median time to achieve reduction to prednisolone dose <5 mg/d was 9 months (95% CI: 7-11). Prednisolone dose could be reduced in all patients while on leflunomide, suggesting steroid-sparing effect and a steroid-free remission could be achieved after a median of 14 months (95% CI: 9.4-18.6). Ultrasonographically, all patients showed improvement of halo signs, after 8 weeks (IQR 7.25-12). Seven patients experienced a clinical relapse after 12 months (IQR: 5-21) of initial remission. The predictors of relapse were duration of symptoms before initiation of immunosuppression therapy and delayed achievement remission by strict criteria. CONCLUSION: This study showed efficacy and safety of leflunomide as a steroid-sparing agent in Indian GCA patients.

High performance BiFeO3 ferroelectric nanostructured photocathodes.

Ferroelectric materials may be used as effective photoelectrocatalysts for water splitting due to enhanced charge carrier separation driven by their spontaneous polarization induced internal electric field. Compared to other ferroelectric materials, BiFeO3 exhibits a high catalytic efficiency due to its comparatively smaller bandgap, which enables light absorption from a large part of the solar spectrum and its higher bulk ferroelectric polarization. Here, we compare the photoelectrochemical properties of three different BiFeO3 morphologies, namely, nanofibers, nanowebs, and thin films synthesized via electrospinning, directly on fluorine-doped tin oxide (FTO) coated glass substrates. A significant photocathodic current in the range from -86.2 to -56.5 µA cm-2 at -0.4 V bias (vs Ag/AgCl) has been recorded for all three morphologies in 0.1M Na2SO4 aqueous solution (pH = 6.8). Among these morphologies, BiFeO3 nanofibers exhibit higher efficiency because of their larger surface area and improved charge separation resulting from rapid diffusion of photoinduced charge carriers along the axis of the nanofiber. In the case of BiFeO3 nanofibers, we obtained the highest photocurrent density of -86.2 µA/cm2 at -0.4 V bias (vs Ag/AgCl electrode) and an onset potential of 0.22 V. We also observed that the onset potential of the photocathodic current can be increased by applying a positive polarization voltage, which leads to favorable bending of band edges at the electrode/electrolyte interface resulting in increased charge carrier separation.

Analysis of Neonatal Outcome with Supplemental Oxygen to Mother during Elective Cesarean Section under Spinal Anesthesia: A Prospective Randomized Controlled Trial.

BACKGROUND: Many questions have arisen on benefits of routine use of supplemental oxygen during elective cesarean section (CS) under spinal anesthesia. AIMS: The aim of this randomized controlled study was to evaluate neonatal outcome in immediate postpartum period with or without supplemental oxygen to mother, undergoing elective CS under spinal anesthesia. MATERIALS AND METHODS: One hundred and thirty-four nonlaboring term pregnant women were allocated randomly into two groups to breathe room air (air group) or oxygen (oxygen group). Times from starting oxygen supplementation to delivery interval, skin incision to delivery (I-D) interval, and uterine incision to delivery (U-D) interval were recorded. APGAR scores were assessed at 1 min and 5 min after delivery. Umbilical cord blood gas analysis was done immediately to measure pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), and bicarbonate. STATISTICAL ANALYSIS: Statistical comparisons were performed using either Student's t-test or Mann-Whitney U-test. RESULTS: For oxygen group versus air group, In Oxygen group, proportion of fetal acidosis was significantly less; umbilical arterial (UA) blood pH (7.22 ± 0.05 vs. 7.19 ± 0.05, P = 0.001) as well as umbilical venous (UV) blood pH (7.26 ± 0.05 vs. 7.22 ± 0.06, P < 0.001) were significantly higher and UA PCO2 (55.4 ± 9.9 vs. 62.9 ± 6.9, P = 0.001) and UV PCO2 (51.4 ± 8.2 vs. 54.3 ± 7.2, P = 0.036) were significantly lower compared to air group. APGAR scores were similar between the groups. CONCLUSIONS: Supplemental oxygen has potential benefits as demonstrated by less proportion of FA in mothers receiving supplemental oxygen.

Direct Observation of Intermediate State(s) in the Mechanistic Investigation of Domain Specific Protein-Surfactant Interaction.

INTRODUCTION: Interaction of surfactants with proteins can decipher important information regarding the stability and behavior of proteins. For multi-domain proteins, these interactions vary domain wise and these details are crucial in understanding the contribution of different domains of the protein in its overall activity. OBJECTIVE: The objective of the present work is to study the interaction of surfactants with domain III of Human Serum Albumin (HSA) and to compare the same with the global interaction. METHODS: Interaction of the anionic Sodium Dodecyl Sulphate (SDS) and the Cationic Cetyltrimethylammonium Bromide (CTAB) surfactants with domain III of Human Serum Albumin (HSA) has been studied using 8-Anilino-1-Naphthalene-Sulphonate (ANS) as a fluorescent marker. Circular Dichroism (CD) spectroscopy has been used to study the protein-surfactant interaction for the overall protein. RESULTS: SDS is found to interact sequentially with domain III of HSA having two detectable intermediate states in the binding process. In case of CTAB, we have observed only one intermediate state for its interaction with domain III. Although Quantum yield measurement can reflect the presence of such intermediate state, the overall conformational change of the HSA on addition of surfactants, studied by Circular Dichroism (CD) spectroscopy, and the ANS-Trp distance measurement by FRET could not resolve the presence of such intermediate states. The esterase activity of HSA in presence of different amount of surfactants is also in accordance with our above observation. CONCLUSION: The interaction of both the surfactants with HSA is found to be sequential in nature. The most important conclusion revealed from our study is that the nature of protein-surfactant interaction is not same throughout the entire protein. Our study reveals that different parts of the multi-domain HSA have different affinity to the surfactant molecules.

Colloidal thallium halide nanocrystals with reasonable luminescence, carrier mobility and diffusion length.

Colloidal lead halide based perovskite nanocrystals (NCs) have been recently established as an interesting class of defect-tolerant NCs with potential for superior optoelectronic applications. The electronic band structure of thallium halides (TlX, where X = Br and I) show a strong resemblance to lead halide perovskites, where both Pb2+ and Tl+ exhibit a 6s2 inert pair of electrons and strong spin-orbit coupling. Although the crystal structure of TlX is not perovskite, the similarities of its electronic structure with lead halide perovskites motivated us to prepare colloidal TlX NCs. These TlX NCs exhibit a wide bandgap (>2.5 eV or <500 nm) and the potential to exhibit a reduced density of deep defect states. Optical pump terahertz (THz) probe spectroscopy with excitation fluence in the range of 0.85-5.86 × 1013 photons per cm2 on NC films shows that the TlBr NCs possess high effective carrier mobility (∼220 to 329 cm2 V-1 s-1), long diffusion length (∼0.77 to 0.98 µm), and reasonably high photoluminescence efficiency (∼10%). This combination of properties is remarkable compared to other wide-bandgap (>2.5 eV) semiconductor NCs, which suggests a reduction in the deep-defect states in the TlX NCs. Furthermore, the ultrafast carrier dynamics and temperature-dependent reversible structural phase transition together with its influence on the optical properties of the TlX NCs are studied.

Colloidal Synthesis and Photophysics of M3 Sb2 I9 (M=Cs and Rb) Nanocrystals: Lead-Free Perovskites.

Herein we report the colloidal synthesis of Cs3 Sb2 I9 and Rb3 Sb2 I9 perovskite nanocrystals, and explore their potential for optoelectronic applications. Different morphologies, such as nanoplatelets and nanorods of Cs3 Sb2 I9 , and spherical Rb3 Sb2 I9 nanocrystals were prepared. All these samples show band-edge emissions in the yellow-red region. Exciton many-body interactions studied by femtosecond transient absorption spectroscopy of Cs3 Sb2 I9 nanorods reveals characteristic second-derivative-type spectral features, suggesting red-shifted excitons by as much as 79 meV. A high absorption cross-section of ca. 10-15  cm2 was estimated. The results suggest that colloidal Cs3 Sb2 I9 and Rb3 Sb2 I9 nanocrystals are potential candidates for optical and optoelectronic applications in the visible region, though a better control of defect chemistry is required for efficient applications.

Suppression of the Coffee-Ring Effect and Evaporation-Driven Disorder to Order Transition in Colloidal Droplets.

The formation of a ring-like deposit at the periphery of a drying colloidal droplet is a vexing problem in many applications. We show a complete suppression of such deposits when a droplet of aqueous colloidal suspension, deposited on a glass substrate coated with a thin layer of silicone oil, is evaporated. This coating prevents the periphery of the aqueous droplet from getting pinned to the substrate and helps in suppressing the ring formation. It also decreases the surface area of the droplet, thereby decreasing the evaporation rate. These two factors together, driving the colloidal particles slowly to the center of the droplet, contribute to form an ordered crystallite at the end of the evaporation process. Brownian dynamics simulations performed to study ordering in the aggregate show that the spherical colloidal particles form face-centered cubic structures. Experiments and simulations show that slow rates of droplet evaporation and smaller-sized colloidal particles further lead to high-quality ordered colloidal crystallites.

Sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic phase.

AIM: This study aimed to assess the sensitivity and specificity of ultrasonographic features of gout in intercritical and chronic stages and compared ultrasonographic features of gout between patients with persistent high serum uric acid (SUA) and patients with low SUA. METHODS: Adult patients with gout confirmed by demonstration of monosodium urate crystals were recruited, if they were in intercritical or chronic stage clinically. Ultrasonographic examination of the first metatarsophalangeal joints (MTPJs) and the knee joints of both sides were done by a blinded rheumatologist trained in musculoskeletal ultrasound. RESULTS: Sixty-two patients with gout and 30 control subjects were examined. The double contour sign (DCS) was found in 71 (57.3%) first MTPJs and tophi were found in 54 (43.5%) first MTPJs. DCS was present in 43 (69.4%) gout patients but none in the control group (P < 0.001). Sensitivity and specificity (95% CI) of DCS in gout patients were 69.4% (56.4-80.4%) and 100% (88.3-100%), respectively, while of tophi they were 66.1% (53-77.7%) and 100% (88.3-100%), respectively. The sensitivity of DCS increased to 100% in high the SUA subgroup (SUA ≥ 7 mg/dL). The low SUA (SUA < 7 mg/dL) gout subgroup showed significantly higher occurrence of erosions (40%) and tophi (50%) in first MTP joints than the control group. CONCLUSION: MSUS is useful for diagnosis of gout in intercritical or chronic stages, especially in patients with persistently high SUA level.

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective.

OBJECTIVE: To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT). METHODS: Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) < 6 mg/dL. RESULTS: Thirty-eight male patients with gout with mean age of 50 ± 11 years, median disease duration of 48 months and baseline mean SUA level of 8.8 ± 1.5 mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance. CONCLUSIONS: Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.

Tuberous Sclerosis and Polycystic Kidney Disease: A Rare Association.

Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two different genetic diseases. Although these two diseases are associated very rarely, the association is well recognized. This occurs due to a large deletion involving both PKD-1 and TSC-2 genes on chromosome 16. This is also known as TSC-2/PKD-1 contiguous gene syndrome. We report a 26-year-old female patient with TSC who presented with severe metabolic acidosis due to renal failure. She had palpable enlarged kidneys bilaterally. CT scan of abdomen revealed bilateral enlarged lobulated kidneys studded with multiple cysts which was consistent with the diagnosis of ADPKD.

Diclofenac is more effective for post-operative analgesia in patients undergoing lower abdominal gynecological surgeries: A comparative study.

AIM: The present study aimed to compare the efficacy of injectable diclofenac intramuscularly (IM), injection paracetamol intravenously (IV), or a combination of both to provide post-operative analgesia in patients undergoing lower abdominal gynecological surgeries. MATERIALS AND METHODS: A total of 90 female patients (American Society of Anesthesiologists I and II), aged 20-50 years, scheduled for elective total abdominal hysterectomy with or without bilateral salpingo-oophorectomy were randomized to receive 75 mg diclofenac IM 8 hourly (Group D) or 1 g paracetamol IV 8 hourly (Group P) or a combination of both 8 hourly (Group PD) for 24 h post-operative period from the start of surgery. The primary outcome measured was the requirement of rescue analgesic (tramadol), the secondary outcomes measured included visual analog score (VAS) for pain, time until first rescue analgesic administration, patient satisfaction score and any side effects. RESULTS: The requirement of rescue analgesic was significantly lower in Groups D and PD compared to Group P. Mean (standard deviation) tramadol requirement during 24 h was 56.67 (62.60) mg, 20.00 (40.68) mg and 20.00 (40.68) mg in the Groups P, D and PD respectively. Less number of patients in Groups D and PD (20% in both the groups) required rescue analgesic compared to Group P (50%). The VAS showed a significant decrease in Groups D and PD compared to Group P between 4 and 12 h post-operatively. However, Group PD showed no significant difference when compared to Group D alone. CONCLUSION: Injection diclofenac IM is more effective than paracetamol IV in terms of rescue analgesic requirement, but the combination of diclofenac IM and paracetamol IV provides no added advantage over diclofenac IM alone.