Concomitant Pulmonary Aspergillosis Following Severe COVID-19.

This case report discusses an atypical complication of COVID-19 pneumonia in a 68-year-old male patient, distinguished by the development of cavitary lung disease and a subsequent incidence of invasive pulmonary aspergillosis (IPA). This adverse development transpired following a prolonged hospitalization and an extensive course of corticosteroid therapy post-COVID-19 pneumonia. This case accentuates the importance of vigilance in observing patients with severe COVID-19 pneumonia for potential opportunistic infections, particularly given the inherent risks associated with prolonged corticosteroid therapy. Prompt diagnosis and initiation of treatment are key to enhancing patient outcomes in such presentations.

Inhibition of melanogenesis by 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone via suppressing the activity of cAMP response element-binding protein (CREB) and nuclear exclusion of CREB-regulated transcription coactivator 1 (CRTC1).

Exposure to Ultraviolet radiation or α-melanocyte-stimulating hormone (α-MSH) stimulates the Cyclic Adenosine Monophosphate/Protein Kinase A signalling pathway, which leads to the synthesis and deposition of melanin granules in the epidermis. Skin pigmentation is the major physiological defence against inimical effects of sunlight. However, excessive melanin production and accumulation can cause various skin hyperpigmentation disorders. The present study involved the identification of 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone (IIIM-8) as an inhibitor of melanogenesis, IIIM-8 significantly inhibited pigment production both in vitro and in vivo without incurring any cytotoxicity in Human Adult Epidermal Melanocytes (HAEM). IIIM-8 repressed melanin synthesis and secretion both at basal levels and in α-MSH stimulated cultured HAEM cells by decreasing the levels of Cyclic Adenosine Monophosphate (cAMP) and inhibiting the phosphorylation of cAMP response element-binding (CREB) protein, coupled with restoring the phosphorylation of CREB-regulated transcription coactivator 1 (CRTC1) and its nuclear exclusion in HAEM cells. This impeding effect correlates with diminished expression of master melanogenic proteins including microphthalmia-associated transcription factor (MITF), Tyrosinase (TYR), Tyrosinase related protein 1 (TRP1), and Tyrosinase related protein 2 (TRP2). Additionally, topical application of IIIM-8 induced tail depigmentation in C57BL/6J mice. Furthermore, IIIM-8 efficiently mitigated the effect of ultraviolet-B radiation on melanin synthesis in the auricles of C57BL/6J mice. This study demonstrates that IIIM-8 is an active anti-melanogenic agent against ultraviolet radiation-induced melanogenesis and other hyperpigmentation disorders.

Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic autophagy.

Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic autophagy. Here, we studied the alterations in hepatocellular autophagy by high cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG), a plant alkaloid, in preventing NAFLD, by modulating autophagy. For this, C57BL/6J mice were fed with Standard Chow (SC) or HC-HF diet, with and without TG for 16 weeks. In-vitro; AML-12 cells and HepG2 cells, were exposed to PA with and without TG, for 24 h. Cellular events related to autophagy, lipogenesis, and lipo-toxicity were studied. The HC-HF diet fed mice showed hepatic autophagy blockade, increased triglycerides and steatosis. PA exposure to AML-12 cells and HepG2 cells induced impaired autophagy, ER stress, resulting in lipotoxicity. TG treatment in HC-HF fed mice, restored hepatic autophagy, and prevented steatosis. TG treated AML-12, and HepG2 cells exposed to PA showed autophagy restoration, and reduced lipotoxicity, however, these effects were diminished in Atg7-/- HepG2 cells, and in the presence of chloroquine. This study shows that HC-HF diet-induced impaired autophagy, and steatosis is prevented by TG, which attributes to its novel mechanism in treating NAFLD.

Anti-inflammatory potential of hentriacontane in LPS stimulated RAW 264.7 cells and mice model.

Hentriacontane, has various pharmacological effects including anti-inflammatory, antitumor and antimicrobial activities. Its anti-inflammatory potential has been demonstrated in peritoneal macrophages. However detailed studies on other models elucidating the mechanistic description of the mode of action has not been done. Hence, the aim of the present study is to evaluate the anti-inflammatory potential of hentriacontane both in-vivo (Balb/c mice) and in-vitro (RAW 264.7 cells). Cytokine inhibition of both pro-inflammatory (TNF-α, IL-6, MCP-1 and IL-1ß) and anti-inflammatory (IL-10) cytokines was studied in RAW 264.7 cells and Balb/c mice. Suppressive potential of hentriacontane on NO, PGE2, LTB4 and on LPS induced translocation of NF-κB in RAW 264.7 cells was studied. Further investigations on the effect of hentriacontane on phagocytic index, carrageenan induced paw oedema in mice and on organ weight were done. It was found that hentriacontane significantly reduced all the parameters of inflammation in the experiments under study at all the concentrations, 10µM, 5µM and 1µM (in-vitro) and 5mg/kg, 2mg/kg and 1mg/kg (in-vivo). The highest concentration used in the two models presented the most significant results. The results indicate that hentriacontane is a potent suppressor of inflammatory cytokines and other mediators. Moreover it also has regulatory effect on NF-κB. Hence, hentriacontane is a potential candidate for investigations to develop anti-inflammatory drug.

Cardiac lymphangioma presenting as intrapericardial cystic mass.

Cystic lymphangioma usually confined to head and neck is a well-recognized tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of disease. We report a case of cystic lymphangioma arising from the right ventricular wall, and presenting as pericardial mass in a young female, who presented with a history of exercise intolerance in the form of breathlessness on exertion and palpitations. The management of such a case was a difficult task; however, she underwent near total resection of the mass, and is doing well for the last 2 years.

Comparative efficacy of long-acting muscarinic antagonists in preventing COPD exacerbations: a network meta-analysis and meta-regression.

BACKGROUND: We hypothesized a class effect of currently available long-acting muscarinic antagonists (LAMAs; i.e., tiotropium as a dry powder inhaler or a soft mist inhaler, aclidinium bromide, and glycopyrronium) in preventing chronic obstructive pulmonary disease (COPD) exacerbations. The hypothesis was tested with a network meta-analysis. METHODS: Several databases and manufacturer's websites were searched for relevant clinical trials. Randomized, controlled trials, of at least 12 weeks duration, comparing a LAMA with placebo or another LAMA were included. Moderate-to-severe and severe exacerbations were chosen as the outcome assessment criteria. The data were pooled using network meta-analysis. RESULTS: A total of 27 studies with 48,140 subjects were included. All LAMAs reduced moderate-to-severe exacerbations compared with placebo. However, there were no statistically significant differences in preventing moderate-to-severe or severe exacerbations among LABAs. In a subgroup analysis restricting studies to those that had a minimum of 6 months of treatment, glycopyrronium was associated with the least-effective strategy and aclidinium was associated with the greatest probability of being the best therapy in preventing severe exacerbations. Our meta-regression analysis suggested that the prevention of COPD exacerbations were less effective in studies which allowed concomitant use of a long-acting beta agonist (LABA). CONCLUSION: All LAMAs were equally effective in preventing moderate-to-severe exacerbations. Aclidinium was associated with the lowest risk for severe exacerbations when treatment duration was 6 months or longer. The concomitant use of LABA may not enhance the efficacy of LAMAs in preventing COPD exacerbations. More studies are needed to further examine above findings.

Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: The choice of vasopressor in septic shock has been a matter of debate. The purpose of this study was to systematically review overall evidence of vasopressor and inotropic agents in septic shock using a Bayesian network meta-analysis. METHODS: Databases, including Medline, Scopus, CINAHL, and Google Scholar were searched to identify relevant studies. Eligible studies were randomized controlled trials that reported mortality rates on the use of vasopressors and inotropes in patients with septic shock. We chose to use 28-day mortality as the outcome assessment criterion. RESULTS: Fourteen studies with a total of 2811 patients were included in the analysis. Norepinephrine (NE) and NE + low-dose vasopressin but not epinephrine (EPI) were associated with significantly reduced mortality compared with dopamine. (Odds ratio, 0.80 [95% credibility interval, 0.65-0.99], 0.69 [0.48-0.98], and 0.56 [0.26-1.18], respectively). The addition of an inotropic agent such as dobutamine or dopexamine did not reduce mortality compared with EPI or NE alone. CONCLUSIONS: Our results support the use of NE with or without low-dose vasopressin as the first-line vasopressor therapy in septic shock. No concrete evidence exists to support the use of EPI over dopamine as the second-line agent or the addition of an inotropic agent.

Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis.

BACKGROUND: A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis. METHODS: Several databases and manufacturer's websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method. RESULTS: Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA. CONCLUSION: ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy.

Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast. METHODS: A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL. Randomized, controlled trials of more than 12 weeks' duration comparing roflumilast with placebo were reviewed. Studies were pooled to yield relative risk (RR), incident rate difference or weighted mean differences with 95% confidence intervals (CIs). RESULTS: Eight trials (8698 patients) met the inclusion criteria. Roflumilast significantly reduced moderate to severe exacerbations (RR 0.85; 95% CI 0.80-0.91) compared with placebo, but not severe exacerbations (RR 0.83; 95% CI 0.68-1.01) or mortality (RR 0.90; 95% CI 0.63-1.28). Roflumilast significantly improved lung function relative to placebo, but not quality of life measures. AEs (RR 1.11; 95% CI 1.03-1.19) and discontinuations of treatment due to AEs (RR 1.63; 95% CI 1.45-1.84) were significantly more frequent with roflumilast than placebo. In the chronic obstructive pulmonary disease (COPD) Safety Pool (12,054 patients), the overall incidence of serious AEs did not differ between groups. However, atrial fibrillation (0.4% versus 0.2%; p = 0.02) and suicidality (0.08% versus 0%) were more frequent with roflumilast than placebo. CONCLUSIONS: The efficacy of roflumilast appears modest compared with other available therapies for COPD. Further studies are needed to investigate the risk-benefit ratio and long-term safety of roflumilast before its wider use.

Left ventricular mass and functions in normotensive offspring of hypertensive parents: an echocardiographic study.

OBJECTIVE: Published observations about cardiovascular alterations in normotensive individuals genetically predisposed to develop essential hypertension are conflicting. We tested the hypothesis that abnormalities in left ventricular mass and/or functions may be present in normotensive children of hypertensive parents. METHODS: One hundred normotensive offsprings (6 to 18 year age) of hypertensive parents (OHP) and an equal number of age- and sex-matched normotensive offsprings of normotensive parents (ONP) were studied with 2-dimensionally guided M-mode and Doppler echocardiography for left ventricular (LV) dimensions, mass, and systolic and diastolic functions. RESULTS: Both the groups had similar body mass index and blood pressure levels. LV dimensions and LV mass in OHP were higher than the corresponding values in ONP but the differences were not statistically significant. LV mass in male OHP was higher than in female OHP; LV mass was also higher when the mother rather than father was hypertensive. None of these differences were statistically significant, however. LV systolic functions were normal and identical in the two subject groups. Indices of LV diastolic function (peak early filling velocity and its deceleration time and late filling velocity) were also normal and similar in the two groups. CONCLUSION: We conclude that children with a family history of essential hypertension have modest alterations in LV mass and these alterations might have a genetic basis separate from but possibly co-inherited with the trait of essential hypertension.

Etiological factors and clinical profile of adhesive capsulitis in patients seen at the rheumatology clinic of a tertiary care hospital in India.

OBJECTIVE: This study was conducted to examine the clinical profile of patients with adhesive capsulitis (AC) and evaluate various possible etiological factors. METHODS: The study was conducted in the Department of Physical Medicine and Rehabilitation, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India. One hundred patients fulfilling the criteria for the diagnosis of AC were studied for the severity of shoulder pain and the range of shoulder movements. The patients were also examined for the presence of various etiological factors for AC. RESULTS: Age of the subjects ranged from 25-70 years and duration of symptoms averaged 3.66 +/- 2.36 months; left shoulder was more commonly involved (54%), 2% had bilateral involvement and 63% of the subjects were sedentary workers. Disease was seen most commonly in patients with diabetes mellitus (27%). Other identifiable risk factors included previous myocardial infarction (5%), immobilization (5%), stroke and chronic bronchitis (4% each). Fifty-six percent of patients with AC had radiological evidence of cervical spondylosis. CONCLUSION: We conclude that AC mostly affects people in the fifth to seventh decade. The majority of the affected individuals are sedentary at the time of the sickness and subjects with diabetes mellitus are at particular risk.