Immunoglobulin G4-related disease - diagnostic dilemma and importance of clinical judgement: a case report

Immunoglobulin G4 (IgG4)-related disease is a multi-organ, immune-mediated, fibro-inflammatory disorder characterized by tumefactive masses in the affected organs. Incidence and prevalence of IgG4-related disease (RD) are not clearly known and have slight male preponderance. It often involves multiple organs at the time of presentation or over the course of disease mimicking malignancy, Sjogren's syndrome, antineutrophil cytoplasmic antibodies associated vasculitis, infections. A thorough workup is needed to rule out these mimickers. A 33-year-old gentleman presented to us with history of progressive swelling in the right peri-orbital region for four years. On evaluation, abdominal imaging was notable for the sausage-shaped pancreas and hypoenchancing nodules in bilateral kidneys. Histological examination of right lacrimal gland revealed lymphoplasmacytic infiltrate and storiform fibrosis. Serum IgG4 levels were normal, and immunostaining was negative. A diagnosis of IgG4-RD was suggested because of multi-organ involvement, classical radiological and histopathological features. Awareness about IgG4-RD, an under-recognized entity is essential, as it is treatable, and early recognition may help in a favourable outcome. Appropriate use of clinicopathological, serological and imaging features in the right clinical context may help in accurate diagnosis. Elevated serum IgG4 levels and biopsy are not mandatory for the diagnosis

Interstitial granulomatous dermatitis: a rare case report of dermatological manifestation of rheumatoid arthritis

Interstitial granulomatous dermatitis (IGD), a rare dermatological disorder was first described by Ackerman et al, in the year 1993. It is characterized by a heterogeneous clinical spectrum and a specific histopathological pattern. It has been described in association with a number of auto-immune disorders, drugs, fungal infections, and malignancies. It may manifest as papules, patches, plaques, nodules, annular lesions, or less frequently, as described classically, as indurated linear subcutaneous cords. This case is being reported as interstitial granulomatous dermatitis is rare dermatological manifestation of rheumatoid arthritis and presentation as large ulcerated skin lesions is further extremely rare. In this case report we describe a 67-year-old gentleman with Seropositive Rheumatoid arthritis. He presented to our hospital with complaints of multiple well defined skin lesions with pus discharge over lower limbs, trunk and upper limbs. Biopsies from left upper limb and abdomen showed focal necrobiosis with surrounding granulomatous inflammation with rare perivascular granulomas. He was subsequently diagnosed to have interstitial granulomatous dermatitis based on histopathological examination. Interstitial granulomatous dermatitis has been described to be associated with a number of autoimmune conditions and drugs. It is very important for clinicians to have knowledge about this rare skin condition as it may be heralding presentation of a serious underlying condition like lymphoproliferative disorders or solid organ malignancies. There is no specific treatment and causative disease has to be diagnosed and targeted

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A study on coagulation profile and clinical outcomes in hospitalized COVID-19 patients in a tertiary care hospital in South India

Introduction: Coagulation abnormalities are a common occurrence in patients with COVID-19, of particular significance is the relationship between D-dimer levels and clinical outcomes. A higher D-dimer level at admission is found to have a poor clinical outcome with increased severity of the disease and increased mortality. Aim and Objectives: To analyze the coagulation profile and its relation to the outcome of patients admitted with COVID-19 pneumonia in a tertiary care center in South India. Subjects and Methods: We conducted a prospective observational study looking at the admission D-dimer, prothrombin time (PT)/international normalized ratio (INR), and platelet levels in 102 admitted COVID-19 patients from February 2021 to January 2022. The relationship between these parameters on admission and the clinical outcome in the form of oxygen requirement, duration of stay, survival, and need for domiciliary oxygen was studied. Discussion and Results: Higher D-dimer levels at admission were associated with poor survival and longer duration of hospital stay with increased requirement of oxygen support. There was a significant correlation between the mean admission D-dimer level and the need for supplemental oxygen (P < 0.05) with patients having a higher D-dimer level at admission (D-dimer of moderate and severe categories: 0.62 ± 0.88 μg/mL and 2.46 ± 4.22 μg/mL, respectively) requiring a higher concentration of oxygen in the form of noninvasive ventilation/high-flow nasal cannula. Furthermore, PT, INR, and platelet count on admission were not useful in predicting the clinical course, oxygen requirement, and overall survival in the study population. Conclusion: Admission levels of D-Dimer can predict the clinical course and outcome of COVID-19 patients

Case report of fatal complication of superior vena cava tear from balloon dilatation of iatrogenic superior vena cava narrowing

The treatment options for superior vena cava (SVC) obstruction depends on the cause and severity of SVC narrowing. It ranges from conservative medical management to more elaborate endovascular and surgical repair of obstruction. There has always been a concern regarding the possibility of rupture of SVC during balloon dilatation, if the obstruction is secondary to the surgical cause. Very few cases are reported in the literature. We report a case of fatal complication of SVC tear in a 2-month-old child who had iatrogenic SVC narrowing

Laboratory investigation of shock-induced dissociation of buckminsterfullerene and astrophysical insights

International audienceFullerene C 60 is one of the most iconic forms of carbon found in the interstellar medium (ISM). The interstellar chemistry of carbon-rich components, including fullerenes, is driven by a variety of energetic processes including UV and X-ray irradiation, cosmic-ray (CR) bombardment, electron impact, and shock waves. These violent events strongly alter the particle phase and lead to the release of new molecular species in the gas phase. Only a few experimental studies on the shock processing of cosmic analogs have been conducted so far. We explored in the laboratory the destruction of buckminsterfullerene C 60 using a pressure-driven shock tube coupled with optical diagnostics. Our efforts were first devoted to probing in situ the shock-induced processing of C 60 at high temperatures (≤ 4500 K) by optical emission spectroscopy. The analysis of the spectra points to the massive production of C 2 units. A broad underlying continuum was observed as well and was attributed to the collective visible emission of carbon clusters, generated similarly in large amounts. This proposed assignment was performed with the help of calculated emission spectra of various carbon clusters. The competition between dissociation and radiative relaxation, determined by statistical analysis, alludes to a predominance of clusters with less than 40 carbon atoms. Our laboratory experiments, supported by molecular dynamics simulations performed in the canonical ensemble, suggest that C 60 is very stable, and that high-energy input is required to process it under interstellar low-density conditions and to produce C 2 units and an abundance of intermediate-sized carbon clusters. These results provide some insights into the life cycle of carbon in space. Our findings hint that only J-type shocks with velocities above ~100 km s −1 or C-type shocks with velocities above 9 km s −1 can lead to the destruction of fullerenes. Observational tracers of this process remain elusive, however. Our work confirms the potential of shock tubes for laboratory astrophysics

Complex macroscale structures formed by the shock processing of amino acids and nucleobases -- implications to the origins of life

The building blocks of life, amino acids and nucleobases, are believed to have been synthesized in the extreme conditions that prevail in space starting from simple molecules containing hydrogen, carbon, oxygen and nitrogen. However, the fate and role of amino acids and nucleobases when they are subjected to similar processes largely remains unexplored. Here we report, for the first time, that shock processed amino acids and nucleobases tend to form complex macroscale structures. Such structures are formed on timescales of about 2 ms. This discovery suggests that the building blocks of life could have polymerized not just on Earth but on other planetary bodies. Our study also provides further experimental evidence for the 'threads' observed in meteorites being due to assemblages of (bio)molecules arising from impact induced shocks.by Vijay Thiruvenkatam et al

Shock Processing of Amino Acids Leading to Complex Structures—Implications to the Origin of Life

The building blocks of life, amino acids, are believed to have been synthesized in the extreme conditions that prevail in space, starting from simple molecules containing hydrogen, carbon, oxygen and nitrogen. However, the fate and role of amino acids when they are subjected to similar processes largely remain unexplored. Here we report, for the first time, that shock processed amino acids tend to form complex agglomerate structures. Such structures are formed on timescales of about 2 ms due to impact induced shock heating and subsequent cooling. This discovery suggests that the building blocks of life could have self-assembled not just on Earth but on other planetary bodies as a result of impact events. Our study also provides further experimental evidence for the &lsquo;threads&rsquo; observed in meteorites being due to assemblages of (bio)molecules arising from impact-induced shocks