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1.
Infection ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856808

ABSTRACT

BACKGROUND: The landscape of Pseudomonas infective endocarditis (IE) is evolving with the widespread use of cardiac implantable devices and hospital-acquired infections. This systematic review aimed to evaluate the emerging risk factors and outcomes in Pseudomonas IE. METHODS: A literature search was performed in major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords and combinations till November 2023. We recorded data for risk factors, diagnostic and treatment modalities. This study is registered with PROSPERO, CRD42023442807. RESULTS: A total of 218 cases (131 articles) were included. Intravenous drug use (IDUs) and prosthetic valve endocarditis (PVE) were major risk factors for IE (37.6% and 22%). However, the prosthetic valve was the predominant risk factor in the last two decades (23.5%). Paravalvular complications (paravalvular leak, abscess, or pseudoaneurysm) were described in 40 cases (18%), and the vast majority belonged to the aortic valve (70%). The mean time from symptom onset to presentation was 14 days. The incidence of difficult-to-treat resistant (DTR) pseudomonas was 7.4%. Valve replacement was performed in 57.3% of cases. Combination antibiotics were used in most cases (77%), with the aminoglycosides-based combination being the most frequently used (66%). The overall mortality rate was 26.1%. The recurrence rate was 11.2%. Almost half of these patients were IDUs (47%), and most had aortic valve endocarditis (76%). CONCLUSIONS: This review highlights the changing epidemiology of Pseudomonas endocarditis with the emergence of prosthetic valve infections. Acute presentation and associated high mortality are characteristic of Pseudomonas IE and require aggressive diagnostic and therapeutic approach.

2.
Cureus ; 16(5): e60659, 2024 May.
Article in English | MEDLINE | ID: mdl-38899239

ABSTRACT

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

3.
Lung India ; 41(2): 98-102, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38700402

ABSTRACT

INTRODUCTION: This study aimed to ascertain the accuracy of clinical examination for the determination of pleural puncture sites as compared to the use of ultrasonography in patients with pleural effusion. MATERIAL AND METHODS: A single-centre, prospective, observational study was carried out amongst 115 patients with pleural effusion in a tertiary care hospital in western India. Patients were subjected to clinical assessment for determination of pleural puncture sites and the same were confirmed with ultrasonography. All physicians were blinded to the marking of the previous physician to prevent any influence on their assessment. RESULTS: The study had 345 physician observations. The overall accuracy of the clinical examination was 94.8%. Multivariate logistic regression of the factors responsible for the accuracy of clinical examination demonstrated a significant role of higher body mass index (BMI) (OR-1.19) and lower zone pleural effusions (OR-4.99) when adjusted for age, gender, side of effusion, and experience of examining doctors. When the effusions were classified according to their location, lower zone pleural effusions and loculated pleural effusions had an error rate of 15.9% and 8.33%, respectively. CONCLUSION: An ultrasound is the standard of care to assess all pleural effusions and guide the best point for aspiration.

4.
Am J Trop Med Hyg ; 110(6): 1217-1222, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38579699

ABSTRACT

Enteric fever is a major contributor to rising health care costs in developing countries. Associated disease-related complications and drug resistance further compound this problem. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon complication of enteric fever with high morbidity and mortality. This systematic review aimed to evaluate the clinical characteristics and treatment outcomes in enteric fever-associated HLH syndrome. We searched major electronic databases (PubMed, Google Scholar, and Scopus) to identify the cases of enteric fever associated with HLH from inception until June 2023. Prespecified data regarding clinical presentation, outcomes, and HLH therapy were collected. A total of 53 cases of enteric fever with HLH were included in the final analysis. The mean age of patients was 20 years, and the proportions of female and pediatric patients were 52.8% and 45.3%, respectively. The mean duration of illness was 10.4 days. A total of 39.6% of patients had enteric fever-associated complications; coagulopathy and encephalopathy were the most common (23.1% and 13.5%). The overall mortality rate was 9.4% in HLH. A total of 51% of patients received HLH-specific therapy (corticosteroids in 41.5% and intravenous immunoglobulin in 20.8% of patients). On multivariate analysis, high ferritin levels (≥5,000 ng/mL) were significantly associated with mortality (hazard ratio, 3.01; 95% CI = 0.62-14.12, P = 0.041). Enteric fever with secondary HLH is associated with high mortality. This review reveals the potential role of ferritin in disease prognosis. In cases with significantly elevated ferritin levels, the role of immunosuppressants or combination antibiotics should be explored.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Typhoid Fever , Lymphohistiocytosis, Hemophagocytic/mortality , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Humans , Typhoid Fever/complications , Typhoid Fever/drug therapy , Typhoid Fever/mortality , Female , Male , Young Adult , Adult , Adolescent , Treatment Outcome , Immunoglobulins, Intravenous/therapeutic use , Child
5.
Trop Parasitol ; 14(1): 36-44, 2024.
Article in English | MEDLINE | ID: mdl-38444794

ABSTRACT

Background: Giardia intestinalis is an intestinal protozoan which commonly causes parasitic gastroenteritis globally. It is a species complex consisting of at least eight assemblages (genotypes). In India, Giardia is mostly underreported and missed in asymptomatic cases. Aim: The aim of this study was to genotype the G. intestinalis isolates from stool samples of patients at a tertiary care center in Rajasthan, India, and to clinically correlate it. Methods: This prospective pilot cross-sectional study was conducted from 2019 to 2021 in a tertiary care center in western India. Patients who were microscopically positive for giardiasis were enrolled. DNA was extracted from their stool samples and amplified by polymerase chain reaction (PCR) using 4E1-HP as the target sequence. Anthropometric measurements and analysis were done for children by using Anthrocal application. Results: A total of 50 patients were enrolled. Diarrhea was present in 18 patients (36%). Among these, 6 were immunocompromised and had different comorbidities. Among the children <12 years of age, 55.17% (n = 16/29) were stunted (<-2 S.D.), and among <5 years, 44.4% (n = 4/9) showed wasting (<-2 S.D.). A PCR product corresponding to assemblage B of G. intestinalis was amplified in 47 stool specimens. Only three stool samples were negative for both assemblages A and B and posed an interesting enigma. Conclusion: In this study, a predominance of assemblage B of G. intestinalis was detected in 94% of the isolates. Furthermore, the possibility of zoonotic transmission could not be ruled out.

6.
Access Microbiol ; 6(2)2024.
Article in English | MEDLINE | ID: mdl-38482345

ABSTRACT

Background: Infections caused by Nocardia spp. can occur in immunocompromised as well as immunocompetent individuals. Although nocardiosis is rare, it is being increasingly recognized owing to the rise in occurrence rate over the years. The documentation of pleural involvement in nocardiosis is rare in India. Case: We report a case of pulmonary nocardiosis in an immunocompromised individual caused by Nocardia otitidiscaviarum. Discussion: Pulmonary nocardiosis caused by Nocardia otitidiscaviarum may go unnoticed without clinical suspicion. Correct and timely identification is the key to proper patient management. Conclusion: Coordination between clinicians and microbiologists is necessary for early diagnosis and appropriate management of nocardiosis.

7.
Germs ; 13(3): 229-237, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38146377

ABSTRACT

Introduction: Gram-positive bloodstream infections (BSIs) are an emerging health concern, especially in resource-limited settings. There is a paucity of data regarding the antimicrobial resistance (AMR) pattern of Gram-positive BSIs. The rise in multidrug-resistant infections further convoluted antibiotic selection. We aimed to assess the incidence, clinical and microbiological profile, antimicrobial resistance (AMR) and outcome in Gram-positive BSIs. Methods: This was a single-center prospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with culture-proven Gram-positive BSIs were included. Data were collected on all patients' demography, risk factors, AMR and clinical outcome. Results: A total of 210 clinically significant isolates were grown from July 2020 to December 2021. The incidence of Gram-positive BSIs was 29% (n=61); 55.9% of cases were healthcare-associated, while 44.1% were community-acquired. Coagulase-negative staphylococci (CoNS) were the major isolates (36.1%), followed by Enterococcus spp. (27.9%), methicillin-susceptible Staphylococcus aureus (MSSA) (18%) and methicillin-resistant Staphylococcus aureus (MRSA) (14.7%). The proportion of vancomycin and teicoplanin-resistant CoNS isolates was 13.6% and 19%. Among Enterococcus isolates, the proportion of vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci (LRE) were 11.8% and 5.9%. The overall mortality in Gram-positive BSIs was 42.6%. Older age, MRSA infection, septic shock, and high NLR were significantly associated with mortality. On the Cox regression model, age ≥65 years (HR: 2.5; 95%CI: 1.1-5.8; p=0.024) and MRSA infection (HR: 3.6; 95%CI: 1.5-8.5; p=0.021) were found as independent predictors of 30-day mortality. Conclusions: This study found substantial mortality with Gram-positive BSIs, especially MRSA infections. Moreover, the emergence of VRE and LRE is also alarming. Active surveillance of AMR and evaluation of mortality predictors may help overcome the therapeutic challenges in managing BSIs.

8.
Indian J Community Med ; 48(5): 734-740, 2023.
Article in English | MEDLINE | ID: mdl-37970173

ABSTRACT

Background: This research aimed to evaluate the clinico-epidemiological profile and short-term outcomes of patients admitted to the emergency department of a tertiary hospital. Materials and Methods: This prospective observational cross-sectional study was conducted between January 1, 2021, and June 30, 2022, in the Emergency Department of a tertiary hospital. Patients of either gender of any age attending the emergency department with acute poisoning were included. These cases were analyzed for their epidemiological profiles, poisoning characteristics, and various clinical variables influencing patient outcomes. Results: Out of a total of 236 patients, 190 patients (80.5%) were aged more than 18 years. Comorbidities were present in 32 (13.5%) patients, and psychiatric illness was the most common comorbidity. The intention of poisoning was suicidal in 185 patients (78.4%) and accidental in 51 patients (21.6%). Organophosphate was the most common poisoning seen in 55 patients (23.3%), followed by drug ingestion seen in 44 patients (18.6%). Twenty-eight patients (11.8%) were transferred to the intensive care unit. Nineteen patients (8.1%) required mechanical ventilation. There were ten deaths (4.2%) in the study population. Aluminum phosphide poisoning was associated with the highest mortality rate, followed by organophosphate poisoning. Conclusions: This study indicates that most poisoning cases involved young people, mainly males. Organophosphorus poisoning was one of the most common poisonings, followed by the ingestion of drugs in this part of the world. Aluminum phosphide had the highest fatality rate.

9.
Cureus ; 15(9): e45034, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37829950

ABSTRACT

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. METHODS:  This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin.  Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. CONCLUSION:  Severe iron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopenia if common causes of pancytopenia are ruled out.

10.
Trop Med Health ; 51(1): 54, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37749661

ABSTRACT

BACKGROUND: CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often treated erroneously as tubercular meningitis or fungal infections. OBJECTIVES: Literature on NTM CNS disease is scarce, with most available data on pulmonary disease. This systematic review aimed to evaluate the epidemiology, clinical presentation, diagnostic modalities, and predictors of outcome in CNS NTM infection. METHODS: The literature search was performed in major electronic databases (PubMed, Google Scholar, and Scopus) using keywords "CNS," "Central nervous system," "brain abscess," "meningitis," "spinal," "Nontuberculous mycobacteria," "NTM". All cases of CNS NTM infection reported between January 1980 and December 2022 were included. RESULTS: A total of 77 studies (112 cases) were included in the final analysis. The mean age of all patients was 38 years, with most patients male (62.5%). Mycobacterium avium complex (MAC) was the most common aetiology, followed by M. fortuitum and M. abscessus (34.8%, 21.4% and 15.2%, respectively). The disseminated disease was found in 33% of cases. HIV (33.9%) and neurosurgical hardware (22.3%) were the common risk factors. Intracranial abscess (36.6%) and leptomeningeal enhancement (28%) were the most prevalent findings in neuroimaging. The overall case fatality rate was 37.5%. On multivariate analysis, male gender (adjusted OR 2.4, 95% CI 1.2-7.9) and HIV (adjusted OR 3.7, 95% CI 1.8-6.1) were the independent predictors of mortality). M. fortuitum infection was significantly associated with increased survival (adjusted OR 0.18, 95% CI (0.08-0.45), p value 0.012). CONCLUSIONS: Current evidence shows the emerging role of rapid-grower NTM in CNS disease. Male gender and HIV positivity were associated with significant mortality, while M fortuitum carries favourable outcomes.

11.
Orphanet J Rare Dis ; 18(1): 133, 2023 06 02.
Article in English | MEDLINE | ID: mdl-37269006

ABSTRACT

BACKGROUND: CNS actinomycosis is a rare chronic suppurative infection with non-specific clinical features. Diagnosis is difficult due to its similarity to malignancy, nocardiosis and other granulomatous diseases. This systematic review aimed to evaluate the epidemiology, clinical characteristics, diagnostic modalities and treatment outcomes in CNS actinomycosis. METHODS: The major electronic databases (PubMed, Google Scholar, and Scopus) were searched for the literature review by using distinct keywords: "CNS" or "intracranial" or "brain abscess" or "meningitis" OR "spinal" OR "epidural abscess" and "actinomycosis." All cases with CNS actinomycosis reported between January 1988 to March 2022 were included. RESULTS: A total of 118 cases of CNS disease were included in the final analysis. The mean age of patients was 44 years, and a significant proportion was male (57%). Actinomycosis israelii was the most prevalent species (41.5%), followed by Actinomyces meyeri (22.6%). Disseminated disease was found in 19.5% of cases. Most commonly involved extra-CNS organs are lung (10.2%) and abdomen (5.1%). Brain abscess (55%) followed by leptomeningeal enhancement (22%) were the most common neuroimaging findings. Culture positivity was found in nearly half of the cases (53.4%). The overall case-fatality rate was 11%. Neurological sequelae were present in 22% of the patients. On multivariate analysis, patients who underwent surgery with antimicrobials had better survival (adjusted OR 0.14, 95% CI 0.04-0.28, p value 0.039) compared to those treated with antimicrobials alone. CONCLUSION: CNS actinomycosis carries significant morbidity and mortality despite its indolent nature. Early aggressive surgery, along with prolonged antimicrobial treatment is vital to improve outcomes.


Subject(s)
Actinomycosis , Central Nervous System Diseases , Humans , Male , Adult , Abscess/complications , Actinomycosis/diagnosis , Actinomycosis/drug therapy , Actinomycosis/epidemiology , Treatment Outcome
12.
Saudi J Anaesth ; 17(2): 290-291, 2023.
Article in English | MEDLINE | ID: mdl-37260652
13.
Indian J Med Microbiol ; 44: 100364, 2023.
Article in English | MEDLINE | ID: mdl-37356828

ABSTRACT

INTRODUCTION: Carbapenem resistant gram-negative bacterial infections are a growing concern worldwide. However, India is already in the era of a shortage of effective antibiotics for the management of these infections. Moreover, Difficult-to-Treat Resistance (DTR) gram-negative infections, which are not much studied, further complicate the scenario. This study emphasized the incidence and outcomes of DTR infections. METHODOLOGY: This is a single-center prospective observational study. The study included hospitalised patients aged ≥18 years with gram-negative bacterial bloodstream infections (GNBSI). Blood cultures with the growth of contaminants and/or single positive culture taken from the femoral site were excluded. Incidences of DTR infections and outcomes in the form of 30-day mortality were analysed. RESULTS: Two hundred forty patients with GNBSI episodes were recorded. The Incidence of DTR GNBSI was 37.9% (91/240). Multivariate analysis found that Hospital-acquired infections, ICU admission and mechanical ventilation were independent risk factors for DTR GNBSI. The most common DTR GNB isolates were Klebsiella pneumoniae (31/49, 63.3%) and Acinetobacter baumannii (26/52, 50%). The adjusted relative risk of mortality was remarkably high in DTR GNBSI (aRR 3.9; 95% CI 1.9-7.9) as compared to CR+/DTR- GNBSI (aRR 0.3; 95% CI 0.1-1.0) and ESCR/CS GNBSI (aRR 1.1; 95% CI 0.5-2.4). CONCLUSION: DTR GNB infections are growing concern in India and this need to be evaluated in multicentric studies. Moreover, DTR GNBSI was associated with significantly higher mortality and there is need of further empowerment of antibiotic stewardship practices.


Subject(s)
Gram-Negative Bacterial Infections , Sepsis , Humans , Adolescent , Adult , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Sepsis/drug therapy , Gram-Negative Bacteria
14.
J Mycol Med ; 33(2): 101380, 2023 May.
Article in English | MEDLINE | ID: mdl-37031499

ABSTRACT

PURPOSE: Invasive cerebral aspergillosis (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021. METHODS: All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, histopathology and serum/CSF galactomannan. RESULTS: A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal brain abscess and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ Aspergillus antigen, Bio-Rad, France) with OD >1 and one patient had high serum galactomannan (OD >2). CSF culture grew Aspergillus species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement. CONCLUSION: Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.


Subject(s)
Aspergillosis , COVID-19 , Humans , Adult , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus , Voriconazole/therapeutic use , France , Mannans , Galactose
15.
Access Microbiol ; 5(1)2023.
Article in English | MEDLINE | ID: mdl-36911424

ABSTRACT

Fungal endocarditis is a rare and fatal condition, most frequently caused by species of the genera Candida and Aspergillus. Fever and changing heart murmur are the most common clinical manifestations. The diagnosis of fungal endocarditis is challenging, with prosthetic valve endocarditis being extremely difficult to diagnose. The optimal management of the condition still remains debatable. We present a case of prosthetic valve endocarditis caused by Candida parapsilosis, managed empirically with liposomal amphotericin B, which was later shifted to combination therapy with high-dose echinocandin and fluconazole, but had a fatal outcome because the patient could not undergo timely surgical intervention. Treating C. parapsilosis endocarditis cases is difficult because of their biofilm production on native and prosthetic heart valves. A combined approach consisting of a high index of clinical suspicion, early diagnosis using serological markers followed by culture or PCR and prompt initiation of appropriate antifungals may aid in improving outcomes.

16.
Arch Physiol Biochem ; 129(6): 1200-1210, 2023 Dec.
Article in English | MEDLINE | ID: mdl-34087084

ABSTRACT

Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Metformin , MicroRNAs , Humans , MicroRNAs/metabolism , Matrix Metalloproteinase 9/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Metformin/pharmacology , Metformin/therapeutic use , Diabetic Nephropathies/metabolism
17.
Minerva Endocrinol (Torino) ; 48(2): 172-185, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35103454

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors. METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR. RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients. CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , MicroRNAs , Prediabetic State , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Prediabetic State/genetics , Prediabetic State/complications , MicroRNAs/genetics , Transcription Factors , Growth Differentiation Factors
18.
J Mycol Med ; 33(1): 101332, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36270213

ABSTRACT

The emergence of Mucorales infections is an urgent global public health threat rapidly disseminating during the current COVID-19 pandemic. Invasive mucormycosis carries significant morbidity and mortality; this is further compounded by the lack of newer effective antifungals on the horizon. Liposomal Amphotericin (L-AMB) is currently considered the cornerstone of antifungals therapy against mucormycosis; However, two decades later (since the introduction of L-AMB), the outcome remains dismal. Furthermore, adverse events related to therapeutic doses of L-AMB are also a hindrance. There is an imperative need for an alternative therapeutic approach to reduce the high mortality. One such approach is to combine the amphotericin with other agents (e.g., caspofungin, posaconazole, isavuconazole, and iron chelators) that can work synergistically or help in reducing the therapeutic doses of L-AMB. This review aims to highlight the various treatment approaches by gathering the clinical evidence from the literature and considering all potential pharmacological combinations that can provide the direction for future studies.


Subject(s)
COVID-19 , Mucormycosis , Humans , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Pandemics
19.
Ann Afr Med ; 21(4): 316-321, 2022.
Article in English | MEDLINE | ID: mdl-36412329

ABSTRACT

Introduction: Hepatitis B virus (HBV) is known as a metabolovirus due to its impact on lipid and glucose metabolism in the liver. Previous literature showed a trend of hypolipidemia and reduced risk of metabolic syndrome in hepatitis B surface antigen-positive patients. However, data from the Indian population are lacking. We evaluate the relation of lipid profile with HBV infection and severity of liver disease. Materials and Methods: This was an observational cross-sectional study in which 50 patients with chronic hepatitis B and 43 anthropometrically matched seronegative controls were enrolled. Demographical, clinical, and laboratory data including lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol [TC]) were collected. Seropositive patients were categorized based on prognostic models (model for end-stage liver disease [MELD] and Child-Pugh score) for further analysis. Results: Our study revealed significant low levels of serum TC, HDL, and LDL cholesterol in hepatitis B patients compared to seronegative controls (133.06 vs. 162.39, 35.56 vs. 43.65, and 76.62 vs. 99.95 mg/dl respectively, P < 0.05). The patients with high MELD and Child-Pugh score were associated with hypolipidemia. Significant low levels of LDL and TC were observed in Child-Pugh class C in comparison to class A (94.8 vs. 149.2 and 50.6 vs. 87.9 mg/dl respectively, P < 0.05). Conclusions: A significant reduction in various lipid parameters was seen with chronic hepatitis B. Furthermore, prognostic score (high MELD and Child-Pugh score) were associated with hypolipidemia.


Résumé Introduction: Le virus de l'hépatite B (VHB) est connu comme un métabolovirus en raison de son impact sur le métabolisme des lipides et du glucose dans le foie. Précédent la littérature a montré une tendance à l'hypolipidémie et à une réduction du risque de syndrome métabolique chez les patients positifs à l'antigène de surface de l'hépatite B. Cependant, les données de la population indienne font défaut. Nous évaluons la relation entre le profil lipidique et l'infection par le VHB et la gravité de la maladie hépatique. Matériels et méthodes: Il s'agissait d'une étude transversale observationnelle dans laquelle 50 patients atteints d'hépatite B chronique et 43 des témoins séronégatifs appariés ont été recrutés. Données démographiques, cliniques et de laboratoire, y compris le profil lipidique (lipoprotéines de haute densité [HDL], lipoprotéines de basse densité [LDL], triglycérides et cholestérol total [TC]) ont été collectés. Les patients séropositifs ont été classés en fonction de modèles pronostiques (modèle pour l'hépatopathie terminale [MELD] et score de Child-Pugh) pour une analyse plus approfondie. Résultats: Notre étude a révélé des taux sériques bas significatifs de cholestérol TC, HDL et LDL chez les patients atteints d'hépatite B par rapport aux témoins séronégatifs (133,06 contre 162,39, 35,56 vs 43,65 et 76,62 vs 99,95 mg/dl respectivement, P < 0,05). Les patients avec un MELD et un score de Child-Pugh élevés étaient associés à hypolipidémie. Des niveaux significativement faibles de LDL et de TC ont été observés dans la classe C de Child-Pugh par rapport à la classe A (94,8 vs. 149,2 et 50,6 vs 87,9 mg/dl respectivement, P < 0,05). Conclusions: Une réduction significative de divers paramètres lipidiques a été observée avec l'hépatite chronique B. De plus, le score pronostique (MELD élevé et score de Child-Pugh) était associé à une hypolipidémie. Mots-clés: Cholestérol, maladie hépatique chronique, hépatite B, hypolipidémie, métabolisme lipidique.


Subject(s)
End Stage Liver Disease , Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/epidemiology , Cross-Sectional Studies , Liver Cirrhosis , Tertiary Care Centers , Cholesterol , Severity of Illness Index , Lipoproteins, HDL , Hepatitis B virus
20.
Clin Neurol Neurosurg ; 222: 107421, 2022 11.
Article in English | MEDLINE | ID: mdl-36067545

ABSTRACT

BACKGROUND AND PURPOSE: To compare Multiphase CT Angiography derived source images (mCTA-SI) in acute ischemic stroke (AIS) with CT Perfusion (CTP) derived automated color maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) and to assess the comparability of mCTA-SI with CTP in the prediction of final radiological and clinical outcome. METHODS: This prospective single-centre observational study comprised of patients with AIS of the anterior circulation, presenting within 24 h and undergoing neuroimaging under stroke protocol with follow-up. Non-contrast computed tomography (NCCT), mCTA, and CTP were acquired with follow-up NCCT at 24 h and modified Rankin score (mRS) at 3 months. mCTA-SI and CTP color maps were scored by the ASPECTS (Alberta Stroke program early CT score) method and compared amongst each other and with the outcome. ROC (Receiver operating characteristic) curves were plotted considering mRS 0-2 and FIV≤ 28 ml as favourable clinical and radiological outcomes respectively. RESULTS: The study included 55 patients. The 1st and 2nd phase of mCTA-SI correlated significantly with CBF maps (r = 0.845, p < 0.01, r = 0.842, p < 0.01 respectively). 3rd phase of mCTA-SI correlated significantly with CBV maps (r = 0.904, p < 0.01). A favourable functional and radiological outcome was best predicted by the 1st (AUC 0.8, 95%CI 0.671-0.896) and 2nd ( AUC 0.895, 95% CI 0.783-0.962) phase of mCTA-SI respectively. CONCLUSIONS: The 1st and 2nd phases of mCTA-SI produces results congruent to CBF color maps and the 3rd phase of mCTA-SI simulate CBV color maps. In addition to predicting radiological and functional outcomes, mCTA can predict the salvageable and non-salvageable tissue in AIS and is non-inferior to CTP.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Brain Ischemia/diagnostic imaging , Cerebral Angiography/methods , Cerebrovascular Circulation , Computed Tomography Angiography/methods , Ischemic Stroke/diagnostic imaging , Perfusion , Prospective Studies , Retrospective Studies , Stroke/diagnostic imaging , Tomography, X-Ray Computed/methods
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