Influence of Time to Achieve Target Systolic Blood Pressure on Outcome After Intracerebral Hemorrhage: The Blood Pressure in Acute Stroke Collaboration.

OBJECTIVE: To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage. METHODS: We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect. RESULTS: A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events. CONCLUSIONS: Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

Reducing Tourniquet Pressures in Hand Surgery: Are Lower Pressures as Effective?

Background Pneumatic tourniquets are widely used in hand surgery. Elevated pressures can be associated with complications, and thus, guidelines based on patient-specific tourniquet pressures have been recommended. The primary aim of this study was to determine whether lower tourniquet values based on systolic blood pressure (SBP) could be effectively applied in upper extremity surgery. Methods A prospective case series of 107 consecutive patients undergoing upper extremity surgery with use of a pneumatic tourniquet was performed. Tourniquet pressure used was based on the patient's SBP. The tourniquet was inflated based on our predetermined guidelines: 60 mm Hg was added for SBP < 130 mm Hg, 80 mm Hg for SBP between 131 and 190 mm Hg, and 100 mm Hg for SBP > 191 mm Hg. The outcome measures included intraoperative tourniquet adjustment, surgeon-rated quality of bloodless operative field and complications. Results The mean tourniquet pressure was 183 ± 26 mm Hg with a mean tourniquet time of 34 minutes (range: 2-120 minutes). There were no instances of intraoperative tourniquet adjustment. The surgeon-rated quality of bloodless operative field was excellent in all patients. No complications were associated with the use of a tourniquet. Conclusion Tourniquet inflation pressure based on SBP is an effective method to provide a bloodless surgical field in upper extremity surgery at significantly lower inflation pressures than are the current standards.

A study on the clinical and electrographic profile of Nonconvulsive Status Epilepticus (NCSE) in comatose ICU patients using portable electroencephalography (EEG).

Background: Coma is one of the frequently encountered clinical conditions in any intensive care unit (ICU), which is responsible for considerable morbidity and mortality. Therefore, this study was designed to look at the clinical and EEG profile of Nonconvulsive Status Epilepticus (NCSE) in comatose ICU patients using portable electroencephalography (EEG). Methods: In all 102 patients of unresponsive coma (GCS ≤ 8), who remained in poor sensorium despite 48 h of optimum treatment in ICU, were included in the study. All patients underwent 1 h of electroencephalography (EEG) monitoring with a portable EEG machine. All EEGs were screened according to Salzburg Consensus Criteria (SCC) for Nonconvulsive Status Epilepticus (NCSE). Patients with evidence of NCSE were administered parenteral Antiepileptic Drugs (AED). A repeat EEG was done after 24 h of baseline to ascertain the effect of AED. The primary outcome was the recognition of patients with NCSE on the basis of established EEG criteria. The secondary outcome measure was the Glasgow outcome scale (GOS) at the time of discharge. Results: Out of 102 cases enrolled, 12 (11.8%) cases were detected to have NCSE on portable EEG. The mean age of patients with NCSE was 52.2 years. In terms of gender distribution, 2/12 (17%) were female, and 10/12 (83%) were male (M: F = 5:1). Median GCS was 6 (range 3-8). Looking at CNS infections, 4/12 (33.3%) had evidence of some form of CNS infection in the NCSE group, compared to 16/90 (18%) in the group without NCSE. This difference was statistically significant (P-value < 0.05). The EEG recordings of patients with NCSE showed dynamicity with fluctuating rhythms and ictal-EEG patterns associated with spatiotemporal evolution. All twelve cases showed reversal of EEG changes with AED administration. In 5 out of 12, transient improvement in GCS (>2 points) after administration of AED' was noted with good clinical outcomes (GOS 5). In five of these 12 cases, death was the final outcome (GOS 1). Conclusions: NSCE should be considered in the differential diagnosis of all unresponsive comatose ICU patients. In resource-limited settings, where continuous EEG monitoring may not be feasible, bedside portable EEG testing can be used to diagnose patients with NCSE. Treating NCSE reverses epileptiform EEG changes and improves clinical outcomes in a subset of comatose ICU patients.

Two unusual cases of Guillain-Barre syndrome after snake bite: the rare immune mediated complication of Elapid venom.

In this report, we present a series of two unusual cases of elapid snakebite with acute neuroparalysis, that after initial response to standard anti-snake venom therapy, developed recurrence of disabling quadriparesis with dysautonomia, that on detailed evaluation turned out to be immune-mediated polyradiculoneuropathy (GB syndrome). Both the cases then responded to therapy with intravenous immunoglobulins. These cases bring out the rare immune-mediated late complication of snake venom, which if recognized and treated in time, can significantly reduce the morbidity and mortality.

Of Eagle's Syndrome and Finding Some Clarity on Its Management.

Eagle's Syndrome is a much discussed yet controversial and debatable diagnosis of exclusion which is treated by many specialities with often unsatisfactory results. Due to entrapment/impingement on surrounding neurovascular structures by elongated styloid process patient may present with multitude of symptoms. Treatment is controversial and opinions are divided on choice of conservative and surgical management. Aim was to study outcomes of conservative and surgical modalities of treatment of Eagle's Syndrome and bring some clarity on management, what to offer, to whom and when. This prospective observational descriptive study included 15 patients of Eagle's Syndrome, 7 were treated with conservative method and 8 underwent resection of styloid process with intraoral approach. With objectives in mind to study efficacy of both management modalities, pain visual analogue scale (VAS) scores were recorded pre-intervention, post-intervention and during follow up on 1, 3 and 6 months and compared. Conservative management resulted in up to 70% reduction in pain VAS scores till 3 months of therapy (mean pre-intervention score being 3.71, 3 months-1, 6 months-1.29), while surgical modality resulted in nearly 99% reduction in mean pain VAS scores up to 3 months and even improved after 6 months (mean pre-intervention score being 6.75, 3 months-0.5, 6 months-0.13). With this we can conclude that conservative management provide satisfactory short-term (up to 3 months) results but recurrences are known, while surgical resection of elongated styloid process gives better long-term results (6 months and beyond).

Frequency of Missed Findings on Chest Radiographs (CXRs) in an International, Multicenter Study: Application of AI to Reduce Missed Findings.

BACKGROUND: Missed findings in chest X-ray interpretation are common and can have serious consequences. METHODS: Our study included 2407 chest radiographs (CXRs) acquired at three Indian and five US sites. To identify CXRs reported as normal, we used a proprietary radiology report search engine based on natural language processing (mPower, Nuance). Two thoracic radiologists reviewed all CXRs and recorded the presence and clinical significance of abnormal findings on a 5-point scale (1-not important; 5-critical importance). All CXRs were processed with the AI model (Qure.ai) and outputs were recorded for the presence of findings. Data were analyzed to obtain area under the ROC curve (AUC). RESULTS: Of 410 CXRs (410/2407, 18.9%) with unreported/missed findings, 312 (312/410, 76.1%) findings were clinically important: pulmonary nodules (n = 157), consolidation (60), linear opacities (37), mediastinal widening (21), hilar enlargement (17), pleural effusions (11), rib fractures (6) and pneumothoraces (3). AI detected 69 missed findings (69/131, 53%) with an AUC of up to 0.935. The AI model was generalizable across different sites, geographic locations, patient genders and age groups. CONCLUSION: A substantial number of important CXR findings are missed; the AI model can help to identify and reduce the frequency of important missed findings in a generalizable manner.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

A Comparative Analysis of Clinical and Imaging Features of Aquaporin 4 (AQP4) Antibody Positive, Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Positive and Double Seronegative Subtypes of Neuro Myelitis Optica Spectrum Disorder (NMOSD).

Objectives: Study was conducted with aim of comparing subtypes types of NMOSD based on serology. Methods: In this retrospective study, patients ≥18 years were included satisfying IPND 2015 criteria. Three groups were created based on seropositivity for AQP4 antibody, MOG antibody or double seronegative. Demographic, clinical and imaging were compared using regression analysis. Results: Forty-six patients, 28 (60.9%) AQP4+, 11 (23.9%) MOG + and remaining 7 (15.2%) double seronegative were included. Thirty-seven patients (80.4%) had presenting symptoms localized to optic nerve and/or cord [AQP4 + 22 (78.5%), MOG + 9 (81.8%) and double seronegative 6 (85.7%)]. Presentation with bilateral optic neuritis was more common in AQP4- patients. Twenty (86.8%) out of the 23 patients who had relapsing disease localized to optic nerve and/or spinal cord [AQP4 + 13/14 (92.8%), MOG + 3/5 (60%) and double seronegative 4/4 (100%)]. Relapses were more common in AQP4+ (77% vs 12% vs10%). In AQP4 negative group disability (EDSS 4.2 vs 3.3) and progression index was relatively less (1.6 vs 1.1). CSF pleocytosis (38.8% vs 17.9%) and raised proteins (66.6% vs 32.1%) were also more common. Optic nerve MRI (>50% optic nerve and chiasma involvement) was more commonly abnormal in AQP4 negative (52.9% vs 31.2%). Regression analysis revealed females to be significantly higher in AQP4 positive NMOSD (89.3%) when compared to MOG positive (36.4%) and double seronegative (42.9%). Conclusion: Gender was the only significant difference between the three groups. There was trend towards greater disability and more relapses in AQP4 + groups.

Efficacy and Safety of Edaravone in Amyotrophic Lateral Sclerosis Patients in Indian Population.

Amyotrophic lateral sclerosis (ALS), is a progressive fatal neurodegenerative disease. It leads to scarring or hardening of Motor neurons. The cause of ALS remains unknown. Oxidative stress caused by free radicals might be an essential factor in the progression of the disease. Edaravone, is a free-radical scavenger, it has been shown to inhibit motor neuron death in animal models by reducing oxidative stress & it has shown efficacy in a small subset of people with ALS. This study was planned to see the efficacy and safety of Edaravone in Indian population. MATERIAL: This study was a single centric observational study, on use of Edaravone in ALS patients. Who were more than 18 years of age and diagnosed to have possible, probable or definite ALS as per the El Escorial Criteria 2014. Total 30 patients were included. All patients had their Revised ALSFRS-R recorded & SFEMG was done at the time of diagnosis then after 6 months of completion of treatment protocol. They were given Edaravone as per as per defined treatment protocol. The treatment protocol consists of 24 weeks (6 cycles). In cycle 1, the study drug was administered for 14 consecutive days followed by a 2 week drug-free period. In cycle 2 and thereafter, the study drug was administered for first 10 days, followed by 18 days drug-free period. The primary efficacy endpoint was a difference in ALSFRS-R score of at least 20% from base line. Secondary endpoints were change in increase in jitter by 10%. Safety endpoints was include the incidence of adverse drug reactions. OBSERVATION: Total of 30 patients were included in the study and 23 patients completed the treatment protocol. 93.3% of patients reported with weakness of limbs while 80% suffered from atrophy of limbs. 96.7% of patients was having fasciculation.2 patients (6.6%) of subjects receiving Edaravone therapy reported with adverse side-effects.After completing the treatment protocol in the study group. On comparing the mean values of ALSFRS-R score at different end-points, no statistical significance was obtained. CONCLUSION: This study failed to demonstrate efficacy of Edaravone to delay the progression of ALS. While the primary desired endpoint was not achieved but there was small improvement in SF-EMG jitter difference of the patients that was not significant statistically. We consider that the study with large sample size results can be helpful to identify the patient population in which Edaravone could be expected to show efficacy.

Clinical Explainability Failure (CEF) & Explainability Failure Ratio (EFR) - Changing the Way We Validate Classification Algorithms.

Adoption of Artificial Intelligence (AI) algorithms into the clinical realm will depend on their inherent trustworthiness, which is built not only by robust validation studies but is also deeply linked to the explainability and interpretability of the algorithms. Most validation studies for medical imaging AI report the performance of algorithms on study-level labels and lay little emphasis on measuring the accuracy of explanations generated by these algorithms in the form of heat maps or bounding boxes, especially in true positive cases. We propose a new metric - Explainability Failure Ratio (EFR) - derived from Clinical Explainability Failure (CEF) to address this gap in AI evaluation. We define an Explainability Failure as a case where the classification generated by an AI algorithm matches with study-level ground truth but the explanation output generated by the algorithm is inadequate to explain the algorithm's output. We measured EFR for two algorithms that automatically detect consolidation on chest X-rays to determine the applicability of the metric and observed a lower EFR for the model that had lower sensitivity for identifying consolidation on chest X-rays, implying that the trustworthiness of a model should be determined not only by routine statistical metrics but also by novel 'clinically-oriented' models.

Early lowering of blood pressure after acute intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

OBJECTIVE: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH). METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect. RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth. INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent. PROSPERO REGISTRATION NUMBER: CRD42019141136.

Validation of expert system enhanced deep learning algorithm for automated screening for COVID-Pneumonia on chest X-rays.

SARS-CoV2 pandemic exposed the limitations of artificial intelligence based medical imaging systems. Earlier in the pandemic, the absence of sufficient training data prevented effective deep learning (DL) solutions for the diagnosis of COVID-19 based on X-Ray data. Here, addressing the lacunae in existing literature and algorithms with the paucity of initial training data; we describe CovBaseAI, an explainable tool using an ensemble of three DL models and an expert decision system (EDS) for COVID-Pneumonia diagnosis, trained entirely on pre-COVID-19 datasets. The performance and explainability of CovBaseAI was primarily validated on two independent datasets. Firstly, 1401 randomly selected CxR from an Indian quarantine center to assess effectiveness in excluding radiological COVID-Pneumonia requiring higher care. Second, curated dataset; 434 RT-PCR positive cases and 471 non-COVID/Normal historical scans, to assess performance in advanced medical settings. CovBaseAI had an accuracy of 87% with a negative predictive value of 98% in the quarantine-center data. However, sensitivity was 0.66-0.90 taking RT-PCR/radiologist opinion as ground truth. This work provides new insights on the usage of EDS with DL methods and the ability of algorithms to confidently predict COVID-Pneumonia while reinforcing the established learning; that benchmarking based on RT-PCR may not serve as reliable ground truth in radiological diagnosis. Such tools can pave the path for multi-modal high throughput detection of COVID-Pneumonia in screening and referral.

Clinical profile and outcome of non-COVID strokes during pandemic and the pre pandemic period: COVID-Stroke Study Group (CSSG) India.

BACKGROUND: As the health systems around the world struggled to meet the challenges of COVID-19 pandemic, care of many non-COVID emergencies was affected. AIMS: The present study examined differences in the diagnosis, evaluation and management of stroke patients during a defined period in the ongoing pandemic in 2020 when compared to a similar epoch in year 2019. METHODS: The COVID stroke study group (CSSG) India, included 18 stroke centres spread across the country. Data was collected prospectively between February and July 2020 and retrospectively for the same period in 2019. Details of demographics, stroke evaluation, treatment, in-hospital and three months outcomes were collected and compared between these two time points. RESULTS: A total of 2549 patients were seen in both study periods; 1237 patients (48.53%) in 2019 and 1312 (51.47%) in 2020. Although the overall number of stroke patients and rates of thrombolysis were comparable, a significant decline was observed in the month of April 2020, during the initial period of the pandemic and lockdown. Endovascular treatment reduced significantly and longer door to needle and CT to needle times were observed in 2020. Although mortality was higher in 2020, proportion of patients with good outcome were similar in both the study periods. CONCLUSIONS: Although stroke admissions and rates of thrombolysis were comparable, some work flow metrics were delayed, endovascular stroke treatment rates declined and mortality was higher during the pandemic study period. Reorganization of stroke treatment pathways during the pandemic has likely improved the stroke care delivery across the globe.

Open-label randomized control trial of hydroxychloroquine in patients with moderate to severe coronavirus disease 2019 infection.

BACKGROUND: At onset of coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) was repurposed for treatment of patients based on reports that it had in vitro activity. The aim of this study was to find out if HCQ reduces number of days of hospitalization when given to patients with moderate to severe COVID-19 infections who require hospitalized care. METHODS: This was an open-label randomized control trial of HCQ administered 400 mg twice on day 1, then 400 mg once daily from day 2 to day 5 in patients with moderate to severe COVID-19 infection. Assessment was not blinded. Standard of care was given to both arms.Primary outcome was number of days of hospitalization till discharge or death. RESULT: One hundred ten patients (55 in each arm) were included. Mean age was 58 years. Baseline characteristics were well matched. There was no difference in the primary outcome (13.67 vs 13.89; p = 0.98). Number of deaths were more in HCQ arm (RR: 1.81; 95% CI: 1.13-2.93; p = 0.03). There was no difference in number of days on oxygen or normalization of oxygen saturation, number who needed ventilator, days to ventilator requirement and days on ventilator. Twenty-nine patients in control arm received remdesivir. When adjusted analysis was done after removal of these patients, there was no difference in primary or secondary outcomes. Number of deaths in adjusted analysis were not significant (RR: 1.28; 95% CI: 0.87-1.88; p = 0.37). CONCLUSION: HCQ does not change the number of days of hospitalization when compared with control.

Myositis in a patient with coronavirus disease 2019: A rare presentation.

The world is presently struggling with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A patient with COVID-19 typically presents with fever, non-productive cough, dyspnea, and myalgia. A 49-year-old female presented with complaints of subacute onset and progressive symmetrical proximal muscle weakness of both upper limbs and lower limbs with no sensory, cranial nerve deficit. She had elevated creatine phosphokinase levels of 906 U/L, an aspartate aminotransferase level of 126 IU/L, a lactate dehydrogenase level of 354 U/L, and an erythrocyte sedimentation rate of 68 mm/1 hr, and magnetic resonance imaging of the pelvis and thigh revealed muscle edema suggestive of myositis. Her reverse transcriptase-polymerase chain reaction result for SARS-CoV-2 was positive. Her evaluation for other causes of myositis was negative. She was managed with intravenous immunoglobulins and supportive care. She showed rapid improvement in symptoms and motor weakness. To our knowledge, this is the first reported case of COVID-19 related disabling myositis in India.

Association of SUMOylation Pathway Genes With Stroke in a Genome-Wide Association Study in India.

OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker-based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10-8. The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p lowest = 1.74 × 10-58) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10-9) and 18-carbon fatty acid metabolism (p = 7.36 × 10-12). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10-6. Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke.