Exploring the necessity of molecular detection for Streptococcus dysgalactiae subsp equisimilis: often misdiagnosed, and emerging pathogen.

BACKGROUND: Streptococcus dysgalactiae subsp equisimilis (SDSE) is an emerging pathogen causing pharyngitis and post-streptococcal sequelae like S. pyogenes. SDSE was initially considered a commensal microorganism inhabiting the upper respiratory tract and skin. However, recently it has gained attention due to an increase in invasive SDSE infections, which were reported in the early 20th century. OBJECTIVES: This review is to bring awareness of SDSE in the medical microbiologists that often leads to the under reporting or misdiagnosis of SDSE. This also highlights the clinical spectrum of infections and the molecular epidemiology of SDSE. CONTENT: Diagnosis of SDSE in clinical laboratories is challenging, because SDSE can be seen expressing either of the three Lancefield antigen Groups, Group A, C, and G. While MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight) is a discriminatory method for identifying SDSE, its high cost can limit its use in many laboratories. Currently, there is limited data on SDSE, and further studies are required to associate the disease outcome and the emm type/ ST of SDSE in India and other developing countries. This review highlights the importance of recognizing SDSE as an emerging pathogen, and to screen for SDSE in infections similar to S.pyogenes, especially in regions such as India with a high incidence of Streptococcal diseases.

Peri-operative Replacement of Exogenous Steroids (PREdS): a national audit of current peri-operative prescribing for patients taking therapeutic steroids.

INTRODUCTION: Approximately 1% of the UK population take oral corticosteroids for ≥ 28 days each year, for broadly two reasons: deficiency in corticosteroid requiring replacement; or therapeutic corticosteroid for inflammatory conditions. Acute deficiency can occur at times of physiological stress (e.g. surgery), potentially leading to major complications. The Association of Anaesthetists' 2020 consensus guideline provides detailed advice for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency. This national audit aimed to assess compliance with this guideline. METHODS: Data were collected from 59 Trusts over 14 consecutive days for all eligible patients undergoing procedures under the care of an anaesthetist. Patients who were prescribed ≥ 5 mg oral prednisolone equivalents pre-operatively, in whom supplementary corticosteroid would be indicated, were compared with those prescribed < 5 mg oral prednisolone equivalents. RESULTS: Operations for 21,731 patients were audited: 277 (1.3%) patients were taking therapeutic corticosteroids. Detailed peri-operative data were collected for all patients receiving therapeutic corticosteroids: 201/277 (73%) were ASA physical status ≥ 3; 184/277 (66%) underwent elective procedures; and 252/277 (91%) were prescribed prednisolone pre-operatively, of whom 219/277 (79%) were prescribed ≥ 5 mg oral prednisolone equivalents. In the patients who were prescribed ≥ 5 mg oral prednisolone equivalents, 186/219 (85%) received pre-operative glucocorticoid supplementation and 97/219 (42%) received it postoperatively; however, only 67/219 (31%) and 43/219 (20%) respectively received glucocorticoid supplementation according to the guidelines. Overall, peri-operative prescribing was compliant in 19/219 (9%) patients. A similar proportion, 30/219 (14%), received no supplementation. In the patients taking < 5 mg oral prednisolone equivalents pre-operatively, 28/58 (48%) received inappropriate supplementation. CONCLUSIONS: Despite 125/277 (45%) of anaesthetists reporting Association of Anaesthetists' guidelines use, compliance remained low, with adherence in only 27/125 (22%) patients. Further research is required to identify the correct peri-operative strategy for patients taking therapeutic corticosteroids.

Evolutionary transition of hypervirulent Klebsiella pneumoniae to multidrug-resistant hypervirulent Klebsiella pneumoniae: Indian experience.

An emerging pathotype of Klebsiella pneumoniae, initially identified in Southeast Asian countries, has now spread to multiple countries, including India. These convergent strains, carrying both resistance and virulence determinants, are classified as multidrug-resistant Hypervirulent Klebsiella pneumoniae (MDR-HvKp). Since the initial reports, there has been a concerning surge in infections caused by this pathotype globally. In this context, we aim to shed light on the evolutionary changes that have taken place in this relatively novel pathotype. Understanding these changes is crucial for devising diagnosis and targeted intervention strategies to mitigate the spread of MDR-HvKp infections.

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: A systematic review.

Background: Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage. Methods: This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration. Results: We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25-5) and the median fragility quotient was 0.015 (IQR 0.02-0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias. Conclusion: Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.

Endovascular Management of Spontaneous Subclavian Artery Dissection.

Spontaneous subclavian artery dissection (SCAD) is a rare clinical observation with very few cases reported in the medical literature. We describe a rare case of a 50-year-old female patient who presented with symptoms of critical limb ischemia of the right upper extremity. A digital subtraction angiogram (DSA) revealed a dissection in the proximal course of the subclavian artery (SCA). Prompt recanalization with endovascular therapy produced an excellent result.

Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats.

Present study aimed to assess effect of pre-treatment with Mucuna pruriens seed extract and its bioactive molecule(s) on NMDAR and Tau protein gene expression in cerebral ischemic rodent model. Methanol extract of M. pruriens seeds was characterized by HPLC, and ß-sitosterol was isolated by flash chromatography. In vivo studies to observe the effect of pre-treatment (28 days) with methanol extract of M. pruriens seed and ß-sitosterol on the unilateral cerebral ischemic rat model. Cerebral ischemia induced by left common carotid artery occlusion (LCCAO) for 75 min (on day 29) followed by reperfusion for 12 h. Rats (n = 48) divided into four groups. GroupI (control,Untreated + LCCAO)-No pre-treatment + cerebral ischemia; GroupII(ß-sitosterol + Sham)-pre-treatment with ß-sitosterol, 10 mg/kg/day + sham-operated; GroupIII(ß-sitosterol + LCCAO)-pre-treatment with ß-sitosterol, 10 mg/kg/day + cerebral ischemia; GroupIV(methanol extract + LCCAO)-pre-treatment with methanol extract of M. pruriens seeds, 50 mg/kg/day + cerebral ischemia. Neurological deficit score was assessed just before sacrifice. Experimental animals were sacrificed after 12 h reperfusion. Brain histopathology was performed. Gene expression of NMDAR and Tau protein of left cerebral hemisphere (occluded side) was performed by RT-PCR. Results revealed that the neurological deficit score was lower in groups III and IV compared to group I. NMDAR and tau protein mRNA expression in left cerebral hemisphere were upregulated in Group I, downregulated in groups III and IV. Histopathology of left cerebral hemisphere (occluded side) in Group I showed features of ischemic brain damage. Groups III and IV, left cerebral hemisphere showed less ischemic damage compared GroupI. Right cerebral hemisphere showed no areas of ischemia-induced brain changes. Pre-treatment with ß-sitosterol and methanol extract of M. pruriens seeds may reduce ischemic brain injury following unilateral common carotid artery occlusion in rats.

Occurrence of Osteochondroma at Unusual Location (Metacarpal): A Rare Case Report.

Introduction: Osteochondroma usually occurs in long bones, whereas smaller bones are less commonly involved. Common locations include metaphysis of the proximal tibia, distal femur, distal tibia, distal fibula, proximal femur, and proximal humerus. Metacarpals are rarely affected. Case Report: A case report of a 20-year- old male presenting with swelling for 5 years, which is gradually increasing in size over the hand and reached 4 cm ×x 3 cm ×x 2 cm; following clinical and radiological examination, the patient was diagnosed with osteochondroma of a fifth metacarpal head of the right hand. We did magnetic resonance imaging scan for confirmation and reported it as osteochondroma which was treated surgically with excision of swelling in total, and specimen sent for histopathology and osteochondroma was confirmed. Conclusion: Osteochondromas can rarely occur at unusual sites such as small bones of the hand and foot. Therefore, osteochondroma should be considered a differential diagnosis alongside other common tumours of the hand and foot, such as enchondroma (Olliers diseases).

Emergence of Meropenem Resistance Among Cefotaxime Non-susceptible Streptococcus pneumoniae: Evidence and Challenges.

The principal causative agent of acute bacterial meningitis (ABM) in children and the elderly is Streptococcus pneumoniae, with a widespread increase in penicillin resistance. Resistance is due to non-synonymous single-nucleotide polymorphisms (nsSNPs) that alter the penicillin-binding proteins (PBPs), the targets for all ß-lactam drugs. Hence, resistance against one ß-lactam antibiotic may positively select another. Since meropenem is an alternative to cefotaxime in meningeal infections, we aim to identify whether nsSNPs in the PBPs causing penicillin and cefotaxime resistance can decrease the pneumococcal susceptibility to meropenem. Comparison of the nsSNPs in the PBPs between the cefotaxime-resistant Indian (n = 33) and global isolates (n = 28) revealed that nsSNPs in PBP1A alone elevated meropenem minimal inhibitory concentrations (MICs) to 0.12 µg/ml, and nsSNPs in both PBP2X and 2B combined with PBP1A increases MIC to ≥ 0.25 µg/ml. Molecular docking confirmed the decrease in the PBP drug binding affinity due to the nsSNPs, thereby increasing the inhibition potential and the MIC values, leading to resistance. Structural dynamics and thermodynamic stability pattern in PBPs as a result of mutations further depicted that the accumulation of certain nsSNPs in the functional domains reduced the drug affinity without majorly affecting the overall stability of the proteins. Restricting meropenem usage and promoting combination therapy with antibiotics having non-PBPs as targets to treat cefotaxime non-susceptible S. pneumoniae meningitis can prevent the selection of ß-lactam resistance.

Beta-Blockade in Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: Sympathetic nervous system activation after aneurysmal subarachnoid hemorrhage (aSAH) is associated with complications and poor outcome. In this systematic review and meta-analysis, we investigate the effect of beta-blockers on outcome after aSAH. METHODS: The review was prospectively registered with PROSPERO (CRD42019111784). We performed a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, published conference proceedings, and abstracts. Eligible studies included both randomized controlled trials and observational studies up to October 2018, reporting the effect of beta-blocker therapy on the following outcomes in aSAH: mortality, vasospasm, delayed cerebral ischemia, infarction or stroke, cardiac dysfunction, and functional outcomes. Studies involving traumatic SAH were excluded. Citations were reviewed, and data extracted independently by two investigators using a standardized proforma. RESULTS: We identified 819 records with 16 studies (four were randomized controlled trials) including 6702 patients selected for analysis. Exposure to beta-blockade either before or after aSAH was associated with a significant reduction in unadjusted mortality (RR 0.63, 95% CI 0.42-0.93, p = 0.02). A significant reduction in unadjusted mortality was also seen in prospective trials of post-event beta-blockade (RR 0.51, 95% CI 0.28-0.93, p = 0.03). Statistically significant differences were not seen for other outcomes investigated. CONCLUSIONS: In adult patients with aSAH, beta-blocker therapy is associated with a mortality benefit. Studies are generally of a low quality with considerable clinical heterogeneity. Prospective large interventional trials with patient centered outcomes are required to validate this finding.

Challenges in predicting ΔrxnG in solution: the mechanism of ether-catalyzed hydroboration of alkenes.

Ab initio (coupled-cluster and density-functional) calculations of Gibbs reaction energies in solution, with new entropy-of-solvation damping terms, were performed for the ether-catalyzed hydroboration of alkenes. The goal was to test the accuracy of continuum-solvation models for reactions of neutral species in nonaqueous solvents, and the hope was to achieve an accuracy sufficient to address the mechanism in the "Pasto case": B2H6 + alkene in THF solvent. Brown's SN2/SN1 "dissociative" mechanism, of SN2 formation of borane-ether adducts followed by SN1 alkene attack, was at odds with Pasto's original SN2/SN2 hypothesis, and while Brown could prove his mechanism for a variety of cases, he could not perform the experimental test with THF adducts in THF solvent, where the higher THF concentrations might favor an SN2 second step. Two diboranes were tested: B2H6, used by Pasto, and (9BBN)2 (9BBN = 9-borabicyclo[3.3.1]nonane, C8H15B), used by Brown. The new entropy terms resulted in improved accuracy vs traditional techniques (∼2 kcal mol(-1)), but this accuracy was not sufficient to resolve the mechanism in the Pasto case.

Folie a trois: atypical presentation as shared transient psychotic episode.

Shared psychotic disorder or induced delusional disorder can occur in different clinical settings and profile and is not uncommon. A case of Folie a trois with atypical clinical presentation as shared acute transient episode in a bereavement setting is reported. Suggestibility, close association and intimacy of the affected persons and major stress as psychological trigger act as psychopathological factors.

Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.

OBJECTIVE: Titin gene (TTN) mutations have been described in eight families with hereditary myopathy with early respiratory failure (HMERF). Some of the original patients had features resembling myofibrillar myopathy (MFM), arguing that TTN mutations could be a much more common cause of inherited muscle disease, especially in presence of early respiratory involvement. METHODS: We studied 127 undiagnosed patients with clinical presentation compatible with MFM. Sanger sequencing for the two previously described TTN mutations in HMERF (p.C30071R in the 119th fibronectin-3 (FN3) domain, and p.R32450W in the kinase domain) was performed in all patients. Patients with mutations had detailed review of their clinical records, muscle MRI findings and muscle pathology. RESULTS: We identified five new families with the p.C30071R mutation who were clinically similar to previously reported cases, and muscle pathology demonstrated diagnostic features of MFM. Two further families had novel variants in the 119th FN3 domain (p.P30091L and p.N30145K). No patients were identified with mutations at position p.32450. CONCLUSIONS: Mutations in TTN are a cause of MFM, and titinopathy is more common than previously thought. The finding of the p.C30071R mutation in 3.9% of our study population is likely due to a British founder effect. The occurrence of novel FN3 domain variants, although still of uncertain pathogenicity, suggests that other mutations in this domain may cause MFM, and that the disease is likely to be globally distributed. We suggest that HMERF due to mutations in the TTN gene be nosologically classified as MFM-titinopathy.

Kimura's Disease: A Case Report.

Kimura's disease is a rare, benign, slow-growing chronic inflammatory swelling with a predilection for the head and neck region and almost always with peripheral blood eosinophilia and elevated serum IgE levels. Here, we report a 14-year-old male patient with left-sided cheek swelling. It was painless swelling situated anterior to left ear, of 1 year duration, without any other symptoms. Routine investigations were inconclusive. Excision biopsy revealed the diagnosis of Kimura's disease.

Clinical profiles and symptoms of childhood depression.

The identification of depression poses significant clinical challenges to physicians, parents and teachers. Symptoms of depression may differ from those of the adult depression. Clinical depression varies in the nature and intensity of its presenting symptoms. It may present with the cardinal symptoms of major depressive disorder. It often goes unidentified and undiagnosed when it presents as masked depression or depressive equivalents.

Boundary crossings and violations in clinical settings.

Principles of beneficence, autonomy, and nonmaleficence, compassion along with fiduciary partnership are the core concepts in the doctor-patient relationship in therapeutic settings. There are varieties of reasons for boundary problems. Physicians ignorance, exploitative character, emotional vulnerability moral weakness and similar factors may pave the way for boundary issues resulting in nonsexual or sexual boundary crossings and violations.

Altered interictal saccadic reaction time in migraine: a cross-sectional study.

AIMS: The underlying mechanisms of migraine remain poorly understood, partly because we lack objective methods for quantitative analysis of neurological function. To address this issue, we measured interictal saccadic latency in migraineurs and controls. METHODS: In a cross-sectional study, we compared interictal saccadic latency distributions of 12,800 saccades in 32 migraineurs with 32 age- and sex-matched controls. RESULTS: The variability of migraineurs' reaction time distributions was significantly smaller (σ = 1.01 vs. 1.13; p < 0.05) compared with controls. In addition, a smaller proportion of migraineurs generated 'early' saccades (31% vs. 56%: p < 0.05). Sensitivity/specificity analysis demonstrated the potential benefit of this technique to diagnostic discrimination. CONCLUSIONS: The migraineur's brain behaves significantly differently from that of a control during the interictal period. By analysing whole distributions, rather than just means, data can be related directly to current neurophysiological models: specifically, the observed decrease in variability suggests a functional deficit in the noradrenergic systems influencing the cerebral cortex. From a clinical perspective, this novel method of characterising neurological function in migraine is more rapid, practicable, inexpensive, objective and quantitative than previous methods such as evoked potentials and transcranial magnetic stimulation, and has the potential both to improve current diagnostic discrimination and to help guide future research into the underlying neural mechanisms.

Wilson's disease--a rare psychiatric presentation.

The development of extrapyramidal syndrome characterised by rigidity, bradykinesia, dysphagia and dysarthria in a male individual with four distinct episodes of (mania like) behavioural disturbances with fairly good remission in a time frame of five years, in a male individual, was suspected to develop the neurological manifestations of Wilson's disease and was investigated. In the absence of Kayser-Fleischer ring by slit-lamp examination and with normal copper and ceruloplasmin serum levels, the diagnosis was possible because of the positive findings of the magnetic resonance imaging (MRI) studies and increased 24 hours urinary copper levels with the penicillamine challenge test. The findings and its implications are highlighted and discussed.

Pediatric bipolar disorder.

Clinicians are less sensitive in considering the diagnosis of mania in children because of the variations in clinical presentation and because of the high comorbidity with other psychiatric disorders. More often than the elated and expansive mood, irritability and significant aggression may be the presenting symptoms in these cases. One such case report is discussed highlighting the clinical aspects of pediatric bipolar disorder.