Cerebellar progressive multifocal leucoencephalopathy identified by the shrimp sign.

Progressive multifocal leucoencephalopathy (PML) is a demyelinating disease caused by the John Cunningham (JC) virus, which may get reactivated under certain immunosuppressive states such as AIDS, immunomodulatory therapy and haematological malignancies. PML has been reported rarely even in immunocompetent individuals where no immunodeficiency was present. PML characteristically involves periventricular and juxtacortical white matter. Isolated cerebellar or brainstem PML may be seen rarely. We present a case of a man in his 70s who presented with rapidly progressive cerebellar ataxia, ptosis and bipyramidal signs. Investigations excluded a direct viral cerebellar infection, acute disseminated encephalomyelitis, paraneoplastic cerebellar degeneration or any structural cerebellar lesion. MRI PET study revealed the classical shrimp sign which raised the possibility of cerebellar PML, and the same was confirmed by a positive JC virus PCR in the cerebrospinal fluid. Our patient had no known immune-compromising state, but further workup revealed a low CD4 count suggestive of idiopathic CD4 lymphopenia. The case illustrates the importance of the shrimp sign on MRI, the possibility of cerebellar involvement of PML as well as the need to consider a differential diagnosis of PML even in individuals with no obvious immunocompromised state.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Management of Chiari 1 Malformation and Hydrocephalus in Syndromic Craniosynostosis: A Review.

Chiari 1 malformation and hydrocephalus are frequent findings in multi-suture and syndromic craniosynostosis patients. In this article, we review the pathogenesis, clinical significance, and management options for these conditions with comments from our own experience. The role of premature fusion of skull base sutures leading to a crowded posterior fossa and venous outflow obstruction resulting in impaired cerebrospinal fluid (CSF) absorption is highlighted. Management options are unique in this group and we advocate early (prior to 6 months of age) posterior vault expansion by distraction osteogenesis (DO) in the management of Chiari 1 malformation. Foramen magnum decompression is recommended for a select few either as part of posterior vault expansion or at a later date. Treatment of hydrocephalus, utilizing a ventriculoperitoneal (VP) shunt with preferably a programmable high-pressure valve and anti-siphon device, is required in a small percentage of cases despite successful posterior vault expansion. Patients need to be carefully selected and managed as hydrocephalus often serves as an important cranial vault growth stimulus. Further, they require careful monitoring and thought to ensure the management of these conditions and the timing of any intervention provides the optimal long-term outcome for the patient.

Two Decades of Gla-100-Reflections from the Pivotal Clinical Trials.

The progressive nature of type 2 diabetes mellitus (T2DM) renders the shifting of patients from oral drugs to insulin therapy an inevitability in most patients especially in those with long duration of diabetes. At the turn of the last millennium, neutral protamine Hagedorn (NPH) insulin was still the only long-acting insulin available for people with diabetes. The advent of the first truly long-acting basal insulin, i.e. insulin glargine 100 U/mL (Gla-100) brought to the table a remarkably long duration of action and a very minimal risk of hypoglycemia by due to less pronounced peaks in their action profile. Further, in trying to achieve fasting normoglycemia, Gla-100 has demonstrated remarkably more holistic glucose-lowering efficacy in several pivotal trials compared to other insulin formulations, such as premixed insulin and coformulations-apart from NPH insulin. This article delineates clinical data on the effectiveness of Gla-100 vs. other insulin formulations in the context of T2DM.

Blood pressure intervention levels in preterm infants: pilot randomised trial.

OBJECTIVE: To examine the feasibility of a trial allocating different blood pressure (BP) intervention levels for treatment in extremely preterm infants. DESIGN: Three-arm open randomised controlled trial performed between February 2013 and April 2015. SETTING: Single tertiary level neonatal intensive care unit. PATIENTS: Infants born <29 weeks' gestation were eligible to participate, if parents consented and they did not have a major congenital malformation. INTERVENTIONS: Infants were randomised to different levels of mean arterial BP at which they received cardiovascular support: active (<30 mm Hg), moderate (

Comparison between ropivacaine and bupivacaine in deep topical fornix nerve block anesthesia in patients undergoing cataract surgery by phacoemulsification.

Purpose: In this study, we intend to analyze ropivacaine and bupivacaine in various parameters during phacoemulsification under deep topical fornix nerve block (DTFNB), a known form of nerve block for phacoemulsification. Methods: This prospective randomized study was conducted on 100 patients undergoing elective cataract surgery by phacoemulsification under DTFNB. Patients were divided into two equal groups of fifty patients each, Groups B (bupivacaine) and Group R (ropivacaine). Two sponges, approximately 2 mm × 3 mm dimensions, saturated with either 0.5% bupivacaine or 0.75% ropivacaine were placed deep in the conjunctival fornices to perform the deep topical block. Both groups were evaluated for magnitude of pain and discomfort at various stages of phacoemulsification using a simple pain scoring system. The level of surgeon satisfaction, requirement for supplementary anesthesia, and surgical complications were also evaluated. Quantitative variables between the two groups were compared using unpaired t-test. Qualitative variables were correlated using Chi-square test. Results: Overall demographic parameters of patients were similar in both groups. Similar mean pain scores were found in the ropivacaine and bupivacaine groups, with no statistical significance. Surgical satisfaction and the need for supplemental anesthesia were also statistically insignificant. Conclusion: Ropivacaine is a good alternative for deep topical anesthesia as it has a better safety margin and lesser toxic effect than other comparable local anesthetic agents.

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

OBJECTIVE: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. DESIGN AND METHODS: Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. RESULTS: Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. CONCLUSIONS: The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability.

Newborn infants with bilious vomiting: a national audit of neonatal transport services.

OBJECTIVE: The precautionary approach to urgently investigate infants with bilious vomiting has increased the numbers referred to transport teams and tertiary surgical centres. The aim of this national UK audit was to quantify referrals and determine the frequency of surgical diagnoses with the purpose to inform the consequent inclusion of these referrals in the national 'time-critical' data set. METHODS: A prospective, multicentre UK-wide audit was conducted between 1 August, 2015 and 31 October, 2015. Term infants aged ≤7 days referred for transfer due to bilious vomiting were included. Data at the time of transport and outcomes at 7 days after transfer were collected by the local teams and transferred anonymously for analysis. RESULTS: Sixteen teams contributed data on 165 cases. Teams that consider such transfers as 'time-critical' responded significantly faster than those that do not classify bilious vomiting as time-critical. There was a surgical diagnosis in 22% cases, and 7% had a condition where delayed treatment may have caused bowel loss. Most surgical problems could be predicted by clinical and/or X-ray findings, but two infants with normal X-ray features were found to have a surgical problem. CONCLUSION: The results support the need for infants with bilious vomiting to be investigated for potential surgical pathologies, but the data do not provide evidence for the default designation of such referrals as 'time-critical.' Decisions should be made by clinical collaboration between the teams and, where appropriate, swift transfer provided.

Management of difficult airway in penetrating cervical spine injury.

Management of airway in trauma victim with penetrating cervical/thoracic spine injury has always been a challenge to the anaesthesiologist. Stabilisation of spine during airway manipulation, to prevent any further neural damage, is of obvious concern to the anaesthesiologist. Most anaesthesiologists are not exposed to direct laryngoscopy and intubation in lateral position during their training period. Tracheal intubation in the lateral position may be unavoidable in some circumstances. Difficult airway in an uncooperative patient compounds the problem to secure airway in lateral position. We present a 46-year-old alcoholic, hypertensive, morbidly obese person who suffered a sharp instrument (screwdriver) spinal injury with anticipated difficult intubation; the case was managed successfully.

Acute myocardial infarction due to blunt chest trauma.

We report a case of blunt chest injury following a road accident leading to damage of the left main and left anterior descending coronary arteries causing acute myocardial infarction in a young person.