Underdiagnosis and diagnostic delay in chronic inflammatory demyelinating polyneuropathy

Background: The frequency and causes of underdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) are uncertain. We aimed to assess the frequency and electroclinical features of pre-referral CIDP underdiagnosis and the duration of delay prior to diagnosis and treatment initiation in a tertiary specialist clinic. Methods: We retrospectively investigated 60 consecutive patients attending our Inflammatory Neuropathy Service, between 2015 and 2019, with a final diagnosis of treatment-responsive definite/probable CIDP. We reviewed the clinical and electrophysiological data in light of European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines and determined the frequency, causes and delay in diagnosis of CIDP. Results: An initial alternative diagnosis to that of CIDP had been made in 68.3% (41/60) of patients. The commonest alternative diagnosis was of Guillain–Barré syndrome (GBS) in 23.3% (14/60) patients. Non-GBS underdiagnoses (27/60; 45%) mainly consisted of genetic neuropathy (8/27; 29.6%), diabetic neuropathy (5/27; 18.5%) and chronic idiopathic axonal polyneuropathy (4/27; 14.8%). Non-GBS underdiagnoses were predominantly due to non-recognition of proximal weakness (70.4%), multifocal deficits (18.5%) or proprioceptive loss (7.4%). Electrophysiological misinterpretation was contributory to pre-referral non-GBS underdiagnoses of CIDP in 85% of patients. Mean diagnostic delay in patients with non-GBS underdiagnoses of CIDP was of 21.3 months (range 2–132 months). Conclusion: Underdiagnosis of CIDP is frequent and may lead to significant diagnostic and treatment delay. We suggest that lack of comprehensive and precise attention to typical electroclinical features of CIDP and its diagnostic criteria at the time of initial evaluation are equally contributory to underdiagnoses

DETRIMENTAL EFFECTS OF PESTICIDES ON HEALTH AND ENVIRONMENT

Pesticides are toxic chemicals used for controlling of insects and pests which caused harms to plants or animals. Pesticides also effect the environment as well as human health. They play a vital role in securing of food but they require a number of risks and problems. Therefore, present study is designed to know the pesticide usage and its harmful effects on environment and health of cotton growers. There are 19 rural union councils out of which 4 were selected through simple random sampling. From each selected union council, 2 villages were selected at random and from each selected village, 20 cotton growers were selected randomly thus making a sample size of 160 respondents. A well planned pre-tested and validated interview schedule was prepared for the collection of data from the selected respondents. The collected data were examined by using Statistical Package for Social Sciences (SPSS) for illustration conclusions and making recommendations. A vast majority (90%) of the respondents selected the pesticides on better results, (83.1%) on behalf of multinational company and majority (76.3%) selected pesticides of national company and a significant of majority (70%) of respondents used the gloves whereas a huge majority (85.6%) of respondents weared the mask during pesticide application. It was found that a huge majority (81.9%) of respondents had headache effect, 67.1% had fatigue, and majority (68.8%) had dizziness while 68.1% had skin disorders. Govt. should promote the first aid training program for safety measurement regarding pesticide usage and enhance the protection techniques for environment and health of organisms regarding pesticides effect

Normative brain mapping using scalp EEG and potential clinical application

A normative electrographic activity map could be a powerful resource to understand normal brain function and identify abnormal activity. Here, we present a normative brain map using scalp EEG in terms of relative band power. In this exploratory study we investigate its temporal stability, its similarity to other imaging modalities, and explore a potential clinical application. We constructed scalp EEG normative maps of brain dynamics from 17 healthy controls using source-localised resting-state scalp recordings. We then correlated these maps with those acquired from MEG and intracranial EEG to investigate their similarity. Lastly, we use the normative maps to lateralise abnormal regions in epilepsy. Spatial patterns of band powers were broadly consistent with previous literature and stable across recordings. Scalp EEG normative maps were most similar to other modalities in the alpha band, and relatively similar across most bands. Towards a clinical application in epilepsy, we found abnormal temporal regions ipsilateral to the epileptogenic hemisphere. Scalp EEG relative band power normative maps are spatially stable across time, in keeping with MEG and intracranial EEG results. Normative mapping is feasible and may be potentially clinically useful in epilepsy. Future studies with larger sample sizes and high-density EEG are now required for validation

Mapping preictal and ictal haemodynamic networks using video-electroencephalography and functional imaging

Ictal patterns on scalp-electroencephalography are often visible only after propagation, therefore rendering localization of the seizure onset zone challenging. We hypothesized that mapping haemodynamic changes before and during seizures using simultaneous video-electroencephalography and functional imaging will improve the localization of the seizure onset zone. Fifty-five patients with ≥2 refractory focal seizures/day, and who had undergone long-term video-electroencephalography monitoring were included in the study. ‘Preictal' (30 s immediately preceding the electrographic seizure onset) and ictal phases, ‘ictal-onset'; ‘ictalestablished' and ‘late ictal', were defined based on the evolution of the electrographic pattern and clinical semiology. The functional imaging data were analysed using statistical parametric mapping to map ictal phase-related haemodynamic changes consistent across seizures. The resulting haemodynamic maps were overlaid on co-registered anatomical scans, and the spatial concordance with the presumed and invasively defined seizure onset zone was determined. Twenty patients had typical seizures during functional imaging. Seizures were identified on video-electroencephalography in 15 of 20, on electroencephalography alone in two and on video alone in three patients. All patients showed significant ictal-related haemodynamic changes. In the six cases that underwent invasive evaluation, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone for all patients. The most statistically significant haemodynamic cluster within the presumed seizure onset zone was between 1.1 and 3.5 cm from the invasively defined seizure onset zone, which was resected in two of three patients undergoing surgery (Class I post-surgical outcome) and was not resected in one patient (Class III post-surgical outcome). In the remaining 14 cases, the ictal-onset phase-related maps had a degree of concordance with the presumed seizure onset zone in six of eight patients with structural-lesions and five of six non-lesional patients. The most statistically significant haemodynamic cluster was localizable at sub-lobar level within the presumed seizure onset zone in six patients. The degree of concordance of haemodynamic maps was significantly better (P < 0.05) for the ictal-onset phase [entirely concordant/concordant plus (13/20; 65%) + some concordance (4/20; 20%) = 17/20; 85%] than ictal-established [entirely concordant/concordant plus (5/13; 38%) + some concordance (4/13; 31%) = 9/13; 69%] and late ictal [concordant plus (1/9; 11%) + some concordance (4/9; 44%) = 5/9; 55%] phases. Ictal propagation-related haemodynamic changes were also seen in symptomatogenic areas (9/20; 45%) and the default mode network (13/20; 65%). A common pattern of preictal changes was seen in 15 patients, starting between 98 and 14 s before electrographic seizure onset, and the maps had a degree of concordance with the presumed seizure onset zone in 10 patients. In conclusion, preictal and ictal haemodynamic changes in refractory focal seizures can non-invasively localize seizure onset at sub-lobar/gyral level when ictal scalp-electroencephalography is not helpfu

Impact of natural killer cells on outcomes after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.

Background: Natural killer (NK) cells play a vital role in early immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT). Methods: A literature search was performed on PubMed, Cochrane, and Clinical trials.gov through April 20, 2022. We included 21 studies reporting data on the impact of NK cells on outcomes after HSCT. Data was extracted following the PRISMA guidelines. Pooled analysis was done using the meta-package (Schwarzer et al.). Proportions with 95% confidence intervals (CI) were computed. Results: We included 1785 patients from 21 studies investigating the impact of NK cell reconstitution post-HSCT (8 studies/1455 patients), stem cell graft NK cell content (4 studies/185 patients), therapeutic NK cell infusions post-HSCT (5 studies/74 patients), and pre-emptive/prophylactic NK cell infusions post-HSCT (4 studies/77 patients). Higher NK cell reconstitution was associated with a better 2-year overall survival (OS) (high: 77%, 95%CI 0.73-0.82 vs low: 55%, 95%CI 0.37-0.72; n=899), however, pooled analysis for relapse rate (RR) or graft versus host disease (GVHD) could not be performed due to insufficient data. Higher graft NK cell content demonstrated a trend towards a better pooled OS (high: 65.2%, 95%CI 0.47-0.81 vs low: 46.5%, 95%CI 0.24-0.70; n=157), lower RR (high: 16.9%, 95%CI 0.10-0.25 vs low: 33%, 95%CI 0.04-0.72; n=157), and lower acute GVHD incidence (high: 27.6%, 95%CI 0.20-0.36 vs low: 49.7%, 95%CI 0.26-0.74; n=157). Therapeutic NK or cytokine-induced killer (CIK) cell infusions for hematologic relapse post-HSCT reported an overall response rate (ORR) and complete response (CR) of 48.9% and 11% with CIK cell infusions and 82.8% and 44.8% with NK cell infusions, respectively. RR, acute GVHD, and chronic GVHD were observed in 55.6% and 51.7%, 34.5% and 20%, and 20.7% and 11.1% of patients with CIK and NK cell infusions, respectively. Pre-emptive donor-derived NK cell infusions to prevent relapse post-HSCT had promising outcomes with 1-year OS of 69%, CR rate of 42%, ORR of 77%, RR of 28%, and acute and chronic GVHD rates of 24.9% and 3.7%, respectively. Conclusion: NK cells have a favorable impact on outcomes after HSCT. The optimal use of NK cell infusions post-HSCT may be in a pre-emptive fashion to prevent disease relapse

Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis

BackgroundWe conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).MethodsWe performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsWe analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively.ConclusionCAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion

Allopurinol-Induced Granulomatous Hepatitis: A Case Report and Review of Literature

Liver enzyme elevation is a common reason for referral to a gastroenterologist. Drugs are one of the most common reasons for asymptomatic elevation of liver enzymes. We present here a case of granulomatous hepatitis (GH) secondary to long-term use of allopurinol. An 83-year-old male with a history of chronic gout and hypertension was evaluated for elevation of liver enzymes. He denies any complaints of abdominal pain, nausea, fever, chills, weight loss, night sweats, or yellowness of skin. He denies any use of herbal medications. He was on losartan and allopurinol for years. No new medications reported. Physical examination was unremarkable. Labs showed aspartate transaminase 101 U/L, alanine transaminase 81 U/L, and alkaline phosphatase 645 U/L. Ultrasound of the abdomen showed coarse liver texture. Liver biopsy was done that showed mixed GH. Given negative autoimmune and viral serologies, allopurinol-induced GH was suspected. Allopurinol was held, and repeat liver enzymes were checked in 3 months, which showed improvement in transaminase and alkaline phosphatase levels. This case highlights the importance of reviewing medications carefully when evaluating a patient with liver enzymes elevation, as stopping the offending drug can normalize the abnormalities in liver chemistries and can prevent subsequent expensive testing

Association of Autoimmune Hepatitis and Celiac Disease: Role of Gluten-Free Diet in Reversing Liver Dysfunction

Autoimmune hepatitis (AIH) is a chronic inflammation of liver with unclear etiology. It is frequently associated other autoimmune diseases, and its association with celiac disease (CD) is well established. In this article, we describe the case of a 50-year-old male with long-standing AIH taking azathioprine for 10 years, evaluated for flares in transaminases. Despite adding high-dose corticosteroids, his transaminases and bilirubin remained high. Serology for CD was ordered, which revealed elevated tissue transglutaminase antibody IgG and endomysial IgA, which was further confirmed by endoscopic biopsy. Strict gluten-free diet was advised and now for over 2 years he is in remission with azathioprine and budesonide. This emphasizes the role of gluten-free diet in reversing liver dysfunction in patients with AIH, and clinicians should consider screening for CD in patients with AIH with persistent elevation of liver enzymes despite immunosuppressant treatment