Thamnostylum piriforme, a novel etiological agent of superficial mycosis.

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.

Dobutamine Stress Cardiovascular Magnetic Resonance Derived 2-Dimension Feature Tracking Strain Analysis in Pediatric Population with Anomalous Aortic Origin of Right Coronary Artery.

Anomalous aortic origin of right coronary artery (AAORCA) is associated with myocardial ischemia and sudden cardiac arrest/death. Risk stratification remains challenging and relies upon provocative test results. This study describes the utility of dobutamine stress cardiovascular magnetic resonance (DSCMR) and potential benefit of strain analysis in children with AAORCA. All patients less than 21 years of age with AAORCA who underwent DSCMR between July 2018 and December 2022 were included. Visual wall motion abnormalities (VWMA) at rest and during protocolized increments of dobutamine infusion were assessed. Regional and global left ventricular circumferential (GCS) and radial (GRS) strain using 2-dimension Feature tracking (2D-FT) analysis (cvi42, Circle Cardiovascular Imaging Inc.) were calculated at rest and peak response. Of the total 54 DSCMR studies performed in 51 children with median age (IQR) of 13.5 (11-15) years, FT analysis was reliably performed in 52 (96%) studies. None had VWMA. The absolute change in GCS and GRS from rest to peak dobutamine stress was 4% (1-6%) and 11% (4-18%), respectively. There was no significant difference in GCS and GRS in patients with exertional symptoms vs no/non-exertional symptoms as well as between those considered to be high-risk vs low-risk anatomical features. DSCMR-derived 2D-FT strain analysis is feasible to assess myocardial deformation in children with AAORCA and may enhance this method of provocative testing. Although there were no statically significant differences in GCS and GRS values between high and low-risk subgroups, the absolute change in GCS between rest and peak stress is diminished when compared to normal adult reports.

Mucormycosis and Its Upsurge During COVID-19 Epidemic: An Updated Review.

Although mucormycosis may have reached an epidemic situation during the COVID-19 pandemic, the term was much more familiar even before the COVID-19 period. The year 2020 showed an outbreak of novel coronavirus (SARS-CoV-2) which affected millions of people all over the world. One of the noticeable complications observed to be associated with this disease is mucormycosis. It is an opportunistic infection caused by members of the Order Mucorales existing worldwide and has been commonly reported as a laboratory contaminant for a long time. However, nowadays due to the changes in the host environment, they have been emerging as potent opportunistic pathogens responsible for causing primary infections or coinfections with other diseases eventually resulting in morbidity and even mortality in severe cases. Although immunocompromised patients are more susceptible to this infection, few cases have been reported in immunocompetent individuals. Various risk factors which are responsible for the acquisition of mucormycosis include diabetes mellitus type 2, ketoacidosis, hematological malignancies, organ transplants, and chemotherapy recipients. Among the various etiological agents, Rhizopus is found to be the most common, and rhino-cerebral to be the most frequent clinical presentation. As far as pathogenesis is concerned, host cell invasion, thrombosis, and necrosis are the main events in the progression of this disease. The aim of the present review is to address a complete spectrum of mucormycosis and COVID-19-associated mucormycosis (CAM) in a single article. Both global and Indian scenarios of mucormycosis are taken into account while framing this review.

Stillbirths in India: Current Status, Challenges, and the Way Forward.

Stillbirth is a major public health challenge and a multifaceted issue that leads to significant financial, physical, mental, financial, and psychosocial implications. India has made substantial progress in stillbirth reduction. Yet, many challenges continue and the absolute number of stillbirths remain high. This paper presents the national and state level burden of stillbirths and discusses about the magnitude, risk factors, causes and inequities in stillbirths. A few additional approaches for reduction of preventable stillbirths have been suggested. The authors argue that the institutional mechanisms need to be developed to ensure all stillbirths are registered in a timely manner. There is a need for standard definition for classification of stillbirths and document the cause, to roll-out suitable interventions. There is a need for state specific interventions to address different causes, as Indian states have variable stillbirth rates. The stillbirth audits should be institutionalised as a continuous quality improvement exercise to bring local accountability and reduce stillbirth rate. The healthcare system and providers must be trained to offer bereavement support to the affected mothers and families. These approaches should be implemented through primary healthcare system as well.

Burden, Differentials and Causes of Stillbirths in India: A Systematic Review and Meta Analysis.

India contributes the highest absolute number of stillbirths in the world. This systematic review and meta-analysis was conducted to synthesize the burden, timing and causes of stillbirths in India. Forty-nine reports from 46 studies conducted in 21 Indian states and Union Territories were included. It was found that there was no uniformity/standardization in the definition of stillbirths and in the classification system used to assign the cause. The share of antepartum stillbirths was estimated to be two-third while remaining were intrapartum stillbirths. Maternal conditions and fetal causes were found to be the leading cause of stillbirth in India. The maternal condition was assigned as the commonest cause (25%) followed by fetal (14%), placental cause (13%), congenital malformation (6%) and intrapartum complications (4%). Approximately 20% of the stillbirths were assigned as unknown or unexplained. This review demonstrates that there is a paucity of quality stillbirth data in India. Other than the state level differences in stillbirth rates, no other data is available on inequities in stillbirths in India. There is an urgent need for strengthening availability and quality of stillbirth data in India on both stillbirth rates as well as the causes. There is a need to conduct additional research to know the timing of the stillbirths, causes of death and actual burden. India needs to strengthen stillbirth audits along with registry to find out the modifiable factors and delays for making country specific preventive strategies. The policy makers, academic community and researchers need to work together to ensure accelerated and equitable reduction in stillbirths in India.

Tolerability and efficacy of a reduced dose adenosine stress cardiac magnetic resonance protocol under general anesthesia in infants and children.

BACKGROUND: Intravenous adenosine induces pharmacological stress by causing vasodilatation and thus carries the risk of severe hypotension when combined with vasodilatory effects of anesthetic agents. OBJECTIVE: This study describes our experience with a reduced dose adenosine cardiac magnetic resonance imaging (MRI) protocol in young children under general anesthesia (GA). MATERIALS AND METHODS: This is a retrospective report of all patients from birth to 18 years who underwent adenosine stress cardiac MRI under GA between August 2018 and November 2022. Based on our anecdotal experience of severe adverse effects in patients receiving adenosine infusion under GA and in discussion with the pediatric anesthesia team, we developed a modified protocol starting at a dose of 110 mcg/kg/min with incremental escalation to a full dose of 140 mcg/kg/min to achieve desired hemodynamic effect. RESULTS: Twenty-two children (mean age 6.5 years, mean weight 28 kg) satisfied the inclusion criteria. The diagnoses included Kawasaki disease (7), anomalous aortic origin of left coronary artery (3), anomalous aortic origin of right coronary artery (2), coronary fistula (3), repaired d-transposition of great arteries (2), repaired anomalous left coronary artery from pulmonary artery (2), repaired truncus arteriosus with left coronary artery occlusion (1), extracardiac-Fontan with left coronary artery myocardial bridge (1), and post heart transplantation (1). Nine patients needed dose escalation beyond 110 mcg/kg/min. Two patients had transient hypotension during testing (systemic blood pressure drop > 25 mmHg). No patient developed significant heart block or bronchospasm. Six patients (repeat study in one) demonstrated inducible perfusion defects (27%) on stress perfusion sequences-5 of whom had confirmed significant coronary abnormalities on angiography or direct surgical inspection. CONCLUSION: A reduced/incremental dose adenosine stress cardiac MRI protocol under GA in children is safe and feasible. This avoids severe hypotension which is both unsafe and may result in inaccurate data.

Obstetric Teleconsultation by Using Mobile Phone Technology in COVID Pandemic.

Introduction: Obstetrics teleconsultation is a new concept to enable health-care services in the COVID pandemic by limiting in-person visits. This study describes the methodology of mobile-based teleconsultation, preliminary findings, and the experience of the obstetricians. Material and Methods: The data of pregnant women who got registered for teleconsultation in early phase of COVID pandemic lockdown were reviewed and analyzed. A qualitative analysis was performed to assess the experience of obstetricians (consultants, senior residents, and junior residents) via an online electronic survey. Results: The majority of obstetrics teleconsultations were for routine antenatal care (75%) and fetal medicine consultation (12.3%). Out of 187 women, 29.9% were advised to continue antenatal care at local hospitals, whereas 33.6% were asked to follow up via teleconsultation. Most of the obstetricians (73.68%) felt that they were able to satisfy the pregnant women and rated the teleconsultation satisfactory. Conclusion: Obstetrics telemedicine found to be beneficial for providing routine antenatal care services via reducing physical visits and overcrowding in outpatient departments, promoting antenatal care at local hospitals, and making specialized (maternal-fetal medicine) care accessible even during COVID-19 pandemic.

Challenges and outcomes of pregnancy in an uncorrected Tetralogy of Fallot with pulmonary atresia and major aorta-pulmonary collateral arteries (MAPCA): a case report.

BACKGROUND: Tetralogy of Fallot is a severe type of congenital heart disease (CHD) and one of the leading indirect causes of mortality & morbidity among women with CHD. We came across a rare case of an uncorrected Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in pregnancy. CASE PRESENTATION: We are reporting the challenges in managing a pregnancy of 25-years-old G3 P0110, previous one stillbirth and who was diagnosed to have congenital heart disease during pregnancy following spontaneous abortion. CONCLUSIONS: This case report highlights the role of multidisciplinary care in managing such a high risk case. It also emphasizes the role of cardiac examination of every woman before pregnancy so that definitive treatment or optimization can be done in time for a better outcome.

L-Carnitine and Chronic Kidney Disease: A Comprehensive Review on Nutrition and Health Perspectives.

Progressive segmental glomerulosclerosis is acknowledged as a characteristic of Chronic Kidney Disease (CKD). It is a major health issue that exponentially reduces health and economy and also causes serious morbidity and mortality across the globe. This review is aimed at comprehending the health perspectives of L-Carnitine (LC) as an adjuvant regimen for alleviating CKD and its associated complications. The data were gathered from different online databases such as Science Direct, Google Scholar, ACS publication, PubMed, Springer, etc., using keywords such as CKD/Kidney disease, current epidemiology and its prevalence, LC supplementations, sources of LC, anti-oxidant and anti-inflammatory potential of LC and its supplementation for mimicking the CKD and its associated problem, etc. Various items of literature concerning CKD were gathered and screened by experts based on their inclusion and exclusion criteria. The findings suggest that, among the different comorbidities such as oxidative stress and inflammatory stress, erythropoietin-resistant anemia, intradialytic hypotension, muscle weakness, myalgia, etc., are considered as the most significant onset symptoms in CKD or hemodialysis patients. LC or creatine supplementation provides an effective adjuvant or therapeutic regimen that significantly reduces oxidative and inflammatory stress and erythropoietin-resistant anemia and evades comorbidities such as tiredness, impaired cognition, muscle weakness, myalgia, and muscle wasting. However, no significant changes were found in biochemical alteration such as creatinine, uric acid, urea, etc., after creatine supplementation in a patient with renal dysfunction. The expert-recommended dose of LC or creatine to a patient is approached for better outcomes of LC as a nutritional therapy regimen for CKD-associated complications. Hence, it can be suggested that LC provides an effective nutritional therapy to ameliorate impaired biochemicals and kidney function and to treat CKD and its associated complications.

Astigmatic reduction after dermoid excision in a child with Goldenhar syndrome.

Goldenhar syndrome is a rare congenital disorder. Limbal dermoid associated with this syndrome can cause high astigmatism and amblyopia in children. We report significant reduction in astigmatism, after limbal dermoid excision with lamellar keratoplasty, in a rare case of Goldenhar syndrome. A three-year-old female patient, with left-sided limbal dermoid with high astigmatism and amblyopia, was referred to us for visual rehabilitation. The patient had left-sided limbal dermoid and preauricular appendages. Oral examination revealed bifid labial frenum, a deep antegonial notch on the left side of the mandible and missing left upper central incisor teeth. She was diagnosed as a case of Goldenhar syndrome. Her best-corrected visual acuity was 20 of 20 in the right eye and 20 of 200 in the left eye. Refraction showed astigmatism of 10 diopters in her left eye. She underwent limbal dermoid excision with lamellar keratoplasty in her left eye, after which her astigmatism reduced considerably. Early surgical intervention is recommended in cases of limbal dermoid with high astigmatism as it provides not only good cosmetic but also good visual benefits by early institution of treatment for amblyopia.

Pregnancy in Eisenmenger syndrome: a case series from a tertiary care hospital of Northern India.

BACKGROUND: Despite advances in medical care, we still come across pregnancy in Eisenmenger syndrome. Eisenmenger syndrome represents the severe end of the spectrum for disease in pulmonary artery hypertension associated with CHD. Due to very high maternal and perinatal morbidity and mortality, pregnancy is contraindicated among these women. Current guidelines also recommend that the women who become pregnant should opt for early termination of pregnancy. Here, we present a case series of 11 women of Eisenmenger syndrome and their pregnancy outcome. METHODS: It was a retrospective analysis of 12 pregnancies among 11 women with Eisenmenger syndrome who were managed in a tertiary care referral centre of Northern India. RESULTS: The mean age of these women was 28 ± 4 years (range 22 to 36 years). Almost 80% of them (9/11) were diagnosed with Eisenmenger syndrome during pregnancy. The commonest cardiac lesion was Ventricular Septal defect (54.5%) followed by Atrial Septal defect (27.3%) and Patent Ductus arteriosus (9.1%). Only three women opted for medical termination of pregnancy, rest eight continued the pregnancy or presented late. Pregnancy complications found include pre-eclampsia (50%), abruption (22%), and fetal growth retardation (62.5%). There were three maternal deaths (mortality rate 27%) in postpartum period. CONCLUSION: This case series highlights the delay in diagnosis and treatment of CHD despite improvement in medical care. Women with Eisenmenger syndrome require effective contraception, preconceptional counselling, early termination of pregnancy, and multidisciplinary care.

Impact of Conditioning Regimen and Graft-versus-Host Disease Prophylaxis on The Outcome of Haploidentical Peripheral Blood Stem Cell Transplantation for High-Risk Severe Aplastic Anemia in Children and Young Adults: A Report from the Pediatric Severe Aplastic Anemia Consortium of India.

Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.

Antimicrobial Agents Based on Metal Complexes: Present Situation and Future Prospects.

The rise in antimicrobial resistance is a cause of serious concern since the ages. Therefore, a dire need to explore new antimicrobial entities that can combat against the increasing threat of antibiotic resistance is realized. Studies have shown that the activity of the strongest antibiotics has reduced drastically against many microbes such as microfungi and bacteria (Gram-positive and Gram-negative). A ray of hope, however, was witnessed in early 1940s with the development of new drug discovery and use of metal complexes as antibiotics. Many new metal-based drugs were developed from the metal complexes which are potentially active against a number of ailments such as cancer, malaria, and neurodegenerative diseases. Therefore, this review is an attempt to describe the present scenario and future development of metal complexes as antibiotics against wide array of microbes.

Metabolomics and Network Pharmacology in the Exploration of the Multi-Targeted Therapeutic Approach of Traditional Medicinal Plants.

Metabolomic is generally characterized as a comprehensive and the most copious analytical technique for the identification of targeted and untargeted metabolite diversity in a biological system. Recently, it has exponentially been used for phytochemical analysis and variability among plant metabolites, followed by chemometric analysis. Network pharmacology analysis is a computational technique used for the determination of multi-mechanistic and therapeutic evaluation of chemicals via interaction with the genomes involved in targeted or untargeted diseases. In considering the facts, the present review aims to explore the role of metabolomics and network pharmacology in the scientific validation of therapeutic claims as well as to evaluate the multi-targeted therapeutic approach of traditional Indian medicinal plants. The data was collected from different electronic scientific databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc., using different keywords such as metabolomics, techniques used in metabolomics, chemometric analysis, a bioinformatic tool for drug discovery and development, network pharmacology, methodology and its role in biological evaluation of chemicals, etc. The screened articles were gathered and evaluated by different experts for their exclusion and inclusion in the final draft of the manuscript. The review findings suggest that metabolomics is one of the recent most precious and effective techniques for metabolite identification in the plant matrix. Various chemometric techniques are copiously used for metabolites discrimination analysis hence validating the unique characteristic of herbal medicines and their derived products concerning their authenticity. Network pharmacology remains the only option for the unique and effective analysis of hundreds of chemicals or metabolites via genomic interaction and thus validating the multi-mechanistic and therapeutic approach to explore the pharmacological aspects of herbal medicines for the management of the disease.

Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.

Clinical studies have shown a significant positive correlation between age and the likelihood of being infected with SARS-CoV-2. This increased susceptibility is positively correlated with chronic inflammation and compromised neurocognitive functions. Postmortem analyses suggest that acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), with systemic and lung hyperinflammation, can cause significant morbidity and mortality in COVID-19 patients. Supraphysiological supplemental oxygen, also known as hyperoxia, is commonly used to treat decreased blood oxygen saturation in COVID-19 patients. However, prolonged exposure to hyperoxia alone can cause oxygen toxicity, due to an excessive increase in the levels of reactive oxygen species (ROS), which can overwhelm the cellular antioxidant capacity. Subsequently, this causes oxidative cellular damage and increased levels of aging biomarkers, such as telomere shortening and inflammaging. The oxidative stress in the lungs and brain can compromise innate immunity, resulting in an increased susceptibility to secondary lung infections, impaired neurocognitive functions, and dysregulated hyperinflammation, which can lead to ALI/ARDS, and even death. Studies indicate that lung inflammation is regulated by the central nervous system, notably, the cholinergic anti-inflammatory pathway (CAIP), which is innervated by the vagus nerve and α7 nicotinic acetylcholine receptors (α7nAChRs) on lung cells, particularly lung macrophages. The activation of α7nAChRs attenuates oxygen toxicity in the lungs and improves clinical outcomes by restoring hyperoxia-compromised innate immunity. Mechanistically, α7nAChR agonist (e.g., GAT 107 and GTS-21) can regulate redox signaling by 1) activating Nrf2, a master regulator of the antioxidant response and a cytoprotective defense system, which can decrease cellular damage caused by ROS and 2) inhibiting the activation of the NF-κB-mediated inflammatory response. Notably, GTS-21 has been shown to be safe and it improves neurocognitive functions in humans. Therefore, targeting the α7nAChR may represent a viable therapeutic approach for attenuating dysregulated hyperinflammation-mediated ARDS and sepsis in COVID-19 patients receiving prolonged oxygen therapy.