Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Studies on tenecteplase have been yielding mixed results for several important outcomes at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses. METHODS: PubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systematically searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta-regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality. RESULTS: Ten randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04-1.26), and early neurological improvement (RR 1.53, 95% CI 1.03-2.26). There was no statistically significant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Meta-regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant. CONCLUSIONS: Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times.

Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Solitary and multiple thyroid nodules as predictors of malignancy: a systematic review and meta-analysis.

BACKGROUND: The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter (MNG) has been constantly present for the last few decades. With newer studies yielding mixed results, it was imperative to systematically compile all available literature on the topic. METHODS: PubMed/MEDLINE, Cochrane Central, ScienceDirect, GoogleScholar, International Clinical Trials registry, and reference lists of the included articles were systematically searched for article retrieval. No filter was applied in terms of time, study design, language or country of publication. Rigorous screening as per PRISMA guidelines was undertaken by 2 independent reviewers in order to identify the articles that were most relevant to the topic. RESULTS: Twenty-two studies spanning from 1992 to 2018 were included in this analysis and encompassed 50,321 patients, 44.2% of which belonged to the STN subgroup and 55.37% to the MNG subgroup. MNG was found to be associated with a significantly lower risk of thyroid cancer (OR = 0.76; 95% CI 0.61-0.96) when compared with STN. Papillary carcinoma was the most frequently occurring carcinoma across both groups, followed by follicular and medullary carcinomas. A subgroup analysis was performed to assess the efficacy of the two most commonly employed diagnostic tools i.e. surgery and fine needle aspiration cytology (FNAC), however it yielded nonsignificant results, indicating a comparable usefulness of the two. Another subgroup analysis run on the basis of the presumed iodine status of the participants also yielded nonsignificant results. CONCLUSION: There is a higher incidence of thyroid cancer among patients of STN, however, given the low quality of existing evidence on the topic, it is crucial to conduct larger studies that can establish association with a greater precision.

Aseptic meningitis in Kikuchi-Fujimoto Disease - Rare manifestation of a rare disease.

Kikuchi-Fujimoto Disease (KFD) is a rare disease marked by necrotizing lymphadenitis, often presenting as unilateral cervical lymphadenopathy, along with various extranodal manifestations such as fever, skin rash, hepatosplenomegaly, and arthritis, etc. KFD is thought to be secondary to either a viral infection or an autoimmune process, however, evidence in favor of both models is scarce and non-definitive. We report a case of a young female who presented with persistent high-grade fever, bilateral cervical and axillary lymphadenopathy, and leukopenia. Excisional biopsy of affected lymph nodes revealed well-circumscribed foci of necrosis with karyorrhectic debris and scattered fibrin deposits characteristic of KFD. The patient was promptly initiated on non-steroidal anti-inflammatory drugs (NSAIDs), however, despite an early improvement in symptoms, the patient soon developed aseptic meningitis, a rare neurological complication of KFD. Intravenous followed by oral corticosteroid therapy reported a good prognosis, with no observable residual neurological deficits. Knowledge of the disease and its complications significantly helped in the avoidance of unnecessary investigations and a delay in treatment.

Efficacy of mindfulness-based intervention for the treatment of chronic headaches: A systematic review and meta-analysis.

Background: Mindfulness-based stress reduction/cognitive therapy has attained popularity as an adjunctive treatment for a plethora of medical and psychiatric conditions, however, its impact on chronic headaches is inconclusive. This review aims to assess the impact of MBSR/MBCT in alleviating the symptoms of chronic headaches. Data sources and data selection: PubMed and Cochrane CENTRAL were searched from inception till 1st May 2021. Randomized Control Trials evaluating mindfulness-based stress reduction/cognitive therapy with either passive comparators (usual care) or active comparators (e.g., Health education or cognitive behavioral therapy) for chronic headaches (Migraine, Tension-type, or cluster headaches), which evaluated either headache frequency, pain intensity or headache duration as primary outcome were eligible for inclusion. The Risk of Bias was evaluated using the Cochrane Collaboration's Risk of Bias Tool. Results: A total of ten Randomized Controlled Trials (five on migraine; three on tension-type; two with mixed samples) were evaluated. In comparison to usual care, mindfulness-based stress reduction/cognitive therapy did not illustrate significant changes in headache frequency (MD = -0.14; 95% CI -1.26 to 0.97; P = 0.80; Moderate Certainty), headache duration (MD = -0.27; 95% CI -3.51 to 2.97, P = 0.87; Low Certainty) or pain intensity (MD = -0.19; 95% CI -0.46 to 0.07; P = 0.15; Moderate Certainty). Conclusion: The results found are insignificant for the three primary outcomes, which may be due to the low number of participants and often a high or unclear risk of bias in the randomized control trials included. Perhaps more aggressive clinical trials with a larger sample size effectively demonstrate differences in outcomes before and after therapy for MBSR/MBCT could provide a more significant change.

Gradenigo's syndrome presenting as IX and X cranial nerve palsy without clinically apparent ear infection: A case report and review of literature.

Gradenigo's syndrome (GS) is a triad (otorrhea, abducens nerve palsy, and pain in the trigeminal nerve distribution) of clinical findings that are caused by contiguous spread of petrous apicitis to the nearby neurovascular structures. Petrous apicitis is usually secondary to otitis media but atypical etiologies and absence of the classical triad pose a diagnostic challenge for physicians. We report a rare case of GS in an afebrile 55-year-old male who presented with unilateral headache, dysphagia and hoarseness (IX and X cranial nerve involvement), and diplopia with lateral gaze palsy (VI nerve involvement) in the absence of trigeminal neuralgia or a history of otitis media. Magnetic Resonance Imaging (MRI) revealed hyperintense lesions in the right petrous apex indicating petrous apicitis, the hallmark of GS. Prompt initiation of broad-spectrum antibiotics led to a marked improvement in dysphagia and voice quality on the 4th post-admission day, and complete resolution of symptoms by the end of the fourth week. This shows that GS can present even in the absence of clinically apparent ear infection and cranial nerve palsies may not be limited to the V and VI nerve in all cases. Physicians should be aware of such atypical manifestations as prompt radiological assessment followed by early antibiotics can prevent life-threatening complications from developing.

Development of myocarditis and pericarditis after COVID-19 vaccination in adult population: A systematic review.

Objectives: A clear temporal relationship between myocarditis and pericarditis after COVID-19 vaccination has led to the belief that the vaccine may act as a trigger for these cardiologic complications. The aim of this systematic review is to explore the incidence, clinical presentation, management, and association between them. Methods: We conducted a systematic literature search on Cochrane, MEDLINE, and EMBASE as per guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews). A total of 41 case reports and case series describing 97 patients, and 5 original articles describing 15,585,309 participants were selected as part of this review. Results: Of the 97 reported cases describing vaccine-associated myocarditis/pericarditis, 67 (69%) patients received Pfizer-BioNTech and 25 (25.7%) received Moderna. The mean onset of symptoms after vaccine administration was 3.8 ± 4.5 days with three-quarters developing symptoms after the second dose. Chest pain (n = 88, 90%) and fever (n = 33, 34%) were the most common presenting complaints. Out of 97, 80 (82.5%) patients recovered while 4 (4.1%) patients expired. The pooled incidence of myocarditis and pericarditis extrapolated from original studies is 0.001% and 0.0004%, respectively. In the original studies, nearly all the cases of myocarditis and pericarditis were mild. Chest pain and fever were the most common presenting symptoms. Conclusion: Myocarditis and pericarditis after the COVID-19 vaccine have been reported more in young adult males and are most likely to occur after the second dose of mRNA vaccines. The presentation is mild and the majority of the patients recover either completely or partially.

Leukoencephalopathy due to inhalational and trans-conjunctival heroin abuse: First case report from Pakistan.

INTRODUCTION: and importance: Heroin-induced leukoencephalopathy (HLE) is a rare illness that causes diffuse white matter destruction, leading to acute or subacute development of neurological signs and symptoms. Physicians must be aware of the likely clinical presentation to properly evaluate and diagnose this clinical entity. CASE PRESENTATION: We report the case of a young gentleman who presented with acute stupor following his first instance of heroin vapor inhalation. He later confessed to trans-conjunctival application of the drug as well. His Glasgow Coma Scale (GCS) score improved within four days of admission, however, the neurologic sequalae such as cognitive impairment, spastic paraparesis and urge incontinence only partially resolved at three months. Abnormal white matter hyperintensities with restricted diffusion on brain magnetic resonance imaging and history of heroin abuse led to diagnosis of toxic leukoencephalopathy. CLINICAL DISCUSSION: Leukoencephalopathy with heroin is mostly observed after inhalation (i.e., "chasing the dragon") but other routes of abuse have also been reported. Although a large spectrum of presentations exists, altered mental status, cerebellar dysfunction and fecal/urinary incontinence are the most commonly seen presenting features. Anti-oxidant therapy has shown promising results in terms of treatment. CONCLUSION: The growing rates of opioid use disorders require physicians to be aware of and counsel the patients regarding dangerous neurological sequelae of these drugs.

Perceptions of oncology as a career choice among the early career doctors in Pakistan.

BACKGROUND: Lack of oncologists is a growing global concern. With the rise in cancer burden across the world, the supply-demand mismatch of the oncology workforce is projected to increase. Furthermore, oncology is a low-ranked field of choice among medical students, and without understanding the perceptions and concerns of early-career doctors regarding oncology, any investments made in cancer care will be futile. This study aims to determine the opinions of young doctors and the factors most affecting their preferences in order to devise focused strategies to attract more doctors into oncology. METHODS: A cross-sectional study was conducted on 300 early-career doctors across various public and private hospitals in Pakistan, from March to November 2019. A close-ended, self-administered questionnaire was used to assess their opinions in terms of the workplace environment, scope, and the emotional and financial aspects of oncology. Data was analyzed using SPSS version 23 and the influence (positive or negative) of the perceptions on the choice of oncology as a career was determined by binary logistic regression analysis. RESULTS: Almost three-quarters of the participants did not want a career in oncology. The top positive perceptions about oncology in descending order were: progressive field, gender-neutral, stable working hours, financially healthy, and work-family balance. Top negative perceptions were: lack of oncologic facilities in hospitals, radiation exposure, need for private practice, poor patient prognosis, high patient load, and depressing environment. Participants who attended private medical school (p < 0.10), planned to live abroad (p < 0.10), had an oncologist (p < 0.05), cancer survivor or death due to cancer in the family (p < 0.05), were more likely to adopt oncology as a career. Those who believed that poor patient prognosis can have an impact on career choice were less likely to prefer oncology (p < 0.05). CONCLUSION: Despite the rising cancer burden, early career doctors are reluctant to join oncology. Curricular, infrastructural and policy changes are needed at the level of medical school, oncology training and practice to recruit more young doctors and minimize the existing paucity of the oncologic workforce.

The pathogenesis of COVID-19-induced IgA nephropathy and IgA vasculitis: A systematic review.

OBJECTIVE: IgA nephropathy (IgAN) and IgA vasculitis (IgAV) are part of a similar clinical spectrum. Both clinical conditions occur with the coronavirus disease 2019 (COVID-19). This review aims to recognize the novel association of IgAN and IgAV with COVID-19 and describe its underlying pathogenesis. METHODS: We conducted a systematic literature search and data extraction from PubMed, Cochrane, ScienceDirect, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Our search identified 13 cases reporting IgAV and IgAN associated with COVID-19 infection and 4 cases of IgAN following COVID-19 vaccination. The mean, mode, and median ages of patients were 23.8, 4, and 8 years, respectively. Most cases associated with COVID-19 infection were reported in males (77%). Rash and purpura (85%) were the most common clinical features, followed by gastrointestinal symptoms (62%). In symptomatic cases, skin or renal biopsy and immunofluorescence confirmed the diagnosis of IgAN or IgAV. Most patients were treated with steroids and reported recovery or improvement; however, death was reported in two patients. CONCLUSION: There is a paucity of scientific evidence on the pathogenesis of the association of IgAN and IgAV with COVID-19, which thus needs further study. Current research suggests the role of IgA-mediated immune response, evidenced by early seroconversion to IgA in COVID-19 patients and the role of IgA in immune hyperactivation as the predominant mediator of the disease process. Clinicians, especially nephrologists and paediatricians, need to recognize this association, as this disease is usually self-limited and can lead to complete recovery if prompt diagnosis and treatment are provided.

How common are taste and smell abnormalities in COVID-19? A systematic review and meta-analysis.

OBJECTIVE: Olfactory and gustatory dysfunction (OGD) are important early clinical symptoms of COVID-19. We aim to calculate the pooled prevalence of these symptoms and discuss the likely implications on clinical practice such as their use as screening tools and potential prognosis indicators. METHODS: Using a combination of keywords and medical subject headings, we searched for observational studies in the following five databases: Medline/PubMed, Scopus, Cochrane Library, Web of Science, and Google Scholar. Two authors independently screened and selected the final articles according to the inclusion criteria. Two investigators independently assessed the risk of bias in individual studies using the Newcastle-Ottawa Scale. Heterogeneity and publication bias were also assessed. The reported outcome of the pooled analysis was the prevalence of OGD calculated using a random-effect model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to report results. RESULTS: Seventeen studies with a total sample size of 4149 were included in this meta-analysis. Out of these, 2106 and 2676 patients reported some degree of olfactory and/or gustatory dysfunction with COVID-19, respectively. The reported outcomes were in terms of pooled prevalence, with gustatory dysfunction being 57.33% and olfactory dysfunction being 59.69%, a significantly high occurrence. CONCLUSION: There is a high occurrence of smell and taste impairment in COVID-19. Given the lack of objective testing for detecting OGD in most studies, the high prevalence found is likely to be an underestimation of the true prevalence. This implies that physicians must use them as reliable early indicators of COVID-19 and employ them before using expensive tests.

The association of posterior reversible encephalopathy syndrome with COVID-19: A systematic review.

The rise in Coronavirus disease 2019 (COVID-19) cases is revealing its unique neurological manifestations. In light of the emerging evidence, a possible association with Posterior Reversible Encephalopathy Syndrome (PRES) is being consistently reported. We conducted a systematic literature search on four databases namely Pubmed/MEDLINE, Cochrane, Google Scholar, and Science Direct. After rigorous screening as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a total of 34 articles describing 56 cases were selected as a part of this review. The mean age of the patients was 56.6 ± 15.3 years. The most common clinical presentation of PRES was altered mental status (58.9%) followed by seizures (46.4%) and visual disturbances (23.2%) while hypertension and diabetes mellitus were the most commonly reported comorbidities. 91.1% of the cases reported Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) findings suggestive of PRES in the brain. Symptomatic management was employed in most of the cases to control seizures and blood pressure, and 44 patients (78.5%) fully or partially recovered. The most likely underlying mechanism involves COVID-19 mediated cytokine storm syndrome that leads to endothelial damage and increased permeability of the cerebral vessels, thus causing the characteristic edema of PRES. High neuronal and glial cell expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors also suggests the possibility of direct viral damage. Since timely diagnosis and treatment reports a good prognosis, it is vital for physicians and neurologists to be well-versed with this association.

The Association of Subacute Thyroiditis with COVID-19: a Systematic Review.

The multisystem effects of SARS-CoV-2 encompass the thyroid gland as well. Emerging evidence suggests that SARS-CoV-2 can act as a trigger for subacute thyroiditis (SAT). We conducted a systematic literature search using PubMed/Medline and Google Scholar to identify cases of subacute thyroiditis associated with COVID-19 and evaluated patient-level demographics, major clinical features, laboratory findings and outcomes. In the 21 cases that we reviewed, the mean age of patients was 40.0 ± 11.3 years with a greater female preponderance (71.4%). Mean number days between the start of COVID-19 illness and the appearance of SAT symptoms were 25.2 ± 10.1. Five patients were confirmed to have ongoing COVID-19, whereas the infection had resolved in 16 patients before onset of SAT symptoms. Fever and neck pain were the most common presenting complaints (81%). Ninety-four percent of patients reported some type of hyperthyroid symptoms, while the labs in all 21 patients (100%) confirmed this with low TSH and high T3 or T4. Inflammatory markers were elevated in all cases that reported ESR and CRP. All 21 cases (100%) had ultrasound findings suggestive of SAT. Steroids and anti-inflammatory drugs were the mainstay of treatment, and all patients reported resolution of symptoms; however, 5 patients (23.8%) were reported to have a hypothyroid illness on follow-up. Large-scale studies are needed for a better understanding of the underlying pathogenic mechanisms, but current evidence suggests that clinicians need to recognize the possibility of SAT both in ongoing and resolved COVID-19 infection to optimize patient care.