ALS Cases Research Articles

Local and remote interactions between macrophages and microglia in neurological conditions.

In the central nervous system (CNS) parenchymal macrophages are called microglial cells and have a distinct developmental origin and can self-renew. However, during pathological conditions, when the blood-brain-barrier becomes leaky, including after injury, in multiple sclerosis or with glioblastoma, monocyte-derived macrophages (MDM) infiltrate the CNS and cohabit with microglia. In neurodegenerative diseases such as Alzheimer's disease or ALS, MDM mostly do not enter the CNS, and instead microglia take several identities. In the specific case of ALS, the affected motor neurons are even surrounded locally by microglia, while along the peripheral nerves, by MDM-derived macrophages. The specific functions and interactions of these different myeloid cells are only starting to be recognized, but hold high promise for more targeted therapies.

Reversible sub-acute motor neuron syndrome after mushroom intoxication masquerading as amyotrophic lateral sclerosis

A 56-year-old man presented with rapidly evolving/sub-acute upper and lower motor neuron syndrome in 2015 with significant weakness in the four limbs and the bulbar region. Amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-r) was rated 34/48. On electromyography, there was a diffuse and active denervation in the four limbs and the tongue. A diagnosis of definite ALS according to international criteria was made. Six months later the patient stopped worsening. In the following years he progressively recovered. ALSFRS-r score improved to reach 48/48 in 2021. His neurological examination is normal and electromyography shows no denervation. Inquiry revealed that he presented a few months and, again a few days before onset, a mushroom poisoning. He was used to eating false morels either crude or undercooked and developed muscles cramps, nausea and vertigo. The relationships between this reversible sub-acute motor neuron syndrome and mushroom intoxication are discussed in the light of the recently described cluster in the Alps with a high incidence of ALS cases. Epidemiological investigations showed that all patients, but not their spouses, used to eat crude or undercooked false morels. Such a mushroom contains hydrazines, a known neurotoxic agent. We are not aware of another case of ALS reversal in that cluster area. We propose that a potential mushroom poisoning be thoroughly searched for when facing with a patient with sub-acute or rapidly worsening ALS syndrome.

Alterations of the serum and CSF ferritin levels and the diagnosis and prognosis of amyotrophic lateral sclerosis.

BackgroundThe ALS diagnostic challenges necessitate more robust diagnostic and prognostic methods. A potential biomarker in this regard is the alterations of ferritin levels in the serum and CSF of patients compared to controls.MethodsThe CSF and serum ferritin levels were measured in 50 ALS cases and 50 control patients with predefined exclusion criteria. The ELISA method was utilized for laboratory measurement and was statistically analyzed using the SPSS.ResultsHeightened serum ferritin levels in cases were not statistically significant. However, CSF ferritin levels were significantly higher in ALS patients (P < 0.001). Serum ferritin levels were significantly negatively correlated with the disease duration (P = 0.015) and were significantly positively correlated with the disease progression rate (DPR) (P = 0.012).ConclusionHeightened CSF ferritin levels can be used for the diagnosis of ALS. The correlation between the serum ferritin levels with the DPR and its correlation with the disease duration suggests potential prognostic utilities.

Bone marrow involvement by ATTR amyloid is common in cardiac amyloidosis patients and may signal advanced-stage disease

Abstract Introduction/Objective Amyloidosis encompasses a heterogeneous group of disorders characterized by abnormal deposition of misfolded proteins leading to progressive organ failure. Accurate amyloid typing is essential for proper patient management, as treatment regimens vary dramatically across different types. Bone marrow (BM) biopsy, in conjunction with fat pad aspiration/biopsy, is often the first step in patients with suspected amyloidosis. Although BM involvement by AL amyloid has been previously characterized, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid in BM. Methods/Case Report We retrospectively identified 1469 BM biopsies by querying our reference laboratory database of 19,298 specimens from myriad anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS). These were reviewed for frequency of amyloid types (N=1469), distribution of amyloid deposits (N=139), and clinical phenotypes (N=345), with particular emphases on cardiac involvement. Results (if a Case Study enter NA) We identified the following amyloid types: AL (N=1172; 79.8%), ATTR (transthyretin) (N=240; 16.3%), AH (immunoglobulin heavy chain) (N=38; 2.6%), AA (serum amyloid A) (N=17; 1.2%), and Aβ2M (β2-microglobulin) (N=2; 0.1%). ATTR deposits showed striking predilection for periosteal soft tissue and/or periosteal vessels, and rarely involved BM stroma and/or interstitial vessels, while AL variably involved these compartments. AA primarily involved interstitial vessels. Both AL and ATTR cases commonly had a monoclonal gammopathy (AL: 92.9%; ATTR: 62.5%) with concomitant cardiac amyloidosis (AL: 91.6%; ATTR: 100%). Compared to AL, ATTR patients had higher stage cardiac amyloidosis and lower overall survival. Conclusion ATTR is common in BM, constituting16.3% of cases in our cohort. Rarer amyloid types, such as AA, AH and AB2M can also occur in BM. ATTR was frequently identified in patients with concomitant monoclonal gammopathy, in whom AL may have been suspected. Although ATTR deposits have distinctive morphologic distribution, primarily involving periosteal soft tissue and/or periosteal vessels and rarely involving BM stroma and/or interstitial vessels, there is considerable morphologic overlap with AL. Therefore, it is imperative to type BM amyloidosis, preferably by LC-MS/MS, to ensure proper patient management. Furthermore, BM involvement by ATTR may be a marker for advanced stage of disease.

Compound heterozygous P67S/D91A SOD1 mutations in an ALS family with apparently sporadic case

Objectives: To describe a family with heterozygous P67S and D91A SOD1 mutations. Methods: The ALS profile of the proband was described. SOD1 gene sequencing was performed in the proband and his children. Results: The affected individual presented with progressive left peripheral facial palsy and slow progression with late limb involvement. Unequivocal upper and lower motor neuron signs were present, together with diffuse denervation at myography. The absence of trigeminal involvement excluded a FOSMN syndrome. Pedigree analysis did not show any other ALS case in the family. Genetic analysis of this patient showed P67S and D91A SOD1 mutations. The genetic analysis of the children showed that the mutations were each one carried by a different chromosome. Conclusions: P67S SOD1 mutation has been described in several ALS cases, either with familial or apparently sporadic ALS. The mutation is located in a mutational hotspot and was predicted pathogenic by in silico prediction software. The study of phylogenetic data show that at this codon, the proline is highly conserved throughout species reinforcing causality. Conversely, the D91A variant is known to have a recessive influence. Unilateral motor facial involvement, even after several years, in an ALS patient is unusual. The present case with compound heterozygosity and unusual onset in a patient with apparently sporadic ALS, widens the clinical spectrum of the disease and adds further arguments to support the systematic genetic screening of all ALS cases in referral ALS clinics.

Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

Abstract Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods We included all patients diagnosed with amyloid light-chain or transthyretin (AL/ATTR) CA at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular (LV) endomyocardial biopsy (EMB). Results Patients (n=37) were more often male (92%), with a median age of 72 years (68–81). Lambda+ AL was found in 14/19 AL cases (38%) and kappa+ AL in 5/19 (14%), while TTR was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10–30%), without significant differences between AL and ATTR. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10–23%, range 5–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between ATTR and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance (CMR), the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (ECV; r=0.661, p=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (p=0.035) and N-terminal pro-B-type natriuretic peptide (p=0.002) serum levels. Conclusions Extracellular spaces in CA are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased ECV at CMR and circulating biomarkers than amyloid extent alone. Funding Acknowledgement Type of funding sources: None.

Case report of SOD1 ALS presenting with prominent hearing impairment

Amyotrophic lateral sclerosis is the neurodegenerative disease involving both upper and lower motor neurons. Familial amyotrophic lateral sclerosis (fALS) accounts for almost 10% of all cases of ALS. It is a gradually progressive disease with duration of more than 10 years and occurrence of atypical features such as pain, paraesthesia or urgency micturition. In case of ALS presenting with deafness, riboflavinopathies and madras motor neuron disease must be suspected from Indian subcontinent. Evaluating for ALS genes is important as SOD1 mutation can present with predominant deafness.

Do ecological factors influence the clinical presentation of amyotrophic lateral sclerosis?

ALS phenotype widely vary across patients. It is unclear if different etiologies could justify this variability. Spatial epidemiology could give some hints on the etiology of diseases by identifying clusters and looking for their genetic or environmental causes. The aim of the study was to perform a spatial analysis of ALS cases stratified by their clinical presentation.

Confirmation of early non-bulbar onset of amyotrophic lateral sclerosis in Spanish league soccer players.

ObjectiveSports-related activity has been proposed as a risk factor for ALS, particularly among professionals playing American football and soccer, with a reported prevalence between two and forty times higher than the general population. Early onset (by two decades) was described among Italian soccer players as early as 2005. This study aims to characterise the phenotype of seven Spanish retired professional and semi-professional soccer players. MethodsThe cases were identified using the following sources: (i) personal archives from a leading ALS Unit, (ii) PubMed and specialised websites, and (iii) self-reports of patients in the media. Age and site of onset, survival time, history of trauma, playing position and time between retirement and first symptoms were investigated for soccer players in the Spanish league diagnosed between 2000 and 2020. ResultsSeven ALS cases were identified. The mean age at onset was 41.5 years (SD 9.2, median 45.5, range 31.5–51.2). Onset was bulbar in one individual, while six experienced spinal onset. Three patients had the flail arm syndrome variant. Two cases were goalkeepers, two defenders and three midfielders. Four had a history of trauma (two serious). Survival time for the two deceased patients was 71.8 months. Mean time between retirement and first symptoms was 9.4 years (SD 8.0, median 15.2, range 0.1–17.5). ConclusionsOur study has the largest sample size of non-Italian league soccer professionals and semi-professionals, and our results corroborate early onset (by 23.7 years). Unlike the Italian cohorts, bulbar onset is rare, and upper limb onset is most common.

Simultaneous Analysis of Telomere Lengthes and Cell Surface Antigen in Leukemia by Multicolor Flow-FISH

During the last decade telomere length (TL) and telomerase have been discovered as new biological markers and potential new targets of cancer including malignant hematopoietic disorders. A FLOW-FISH method, i.e. quantitative fluorescence in situ hybridization (Q-FISH) in combination with flow cytometry (FCM), has been developed recently. Most overseas studies detect TL by FLOW-FISH without combined analysis of cell immunophenotype. We analyzed TL and cell immunophenotype simultaneously in the same sample by FLOW-FISH in order to combine the two markers to found one generally applied method for monitoring disease conditions or predicting clinical outcome in leukemia.Methods:HL60, Raji, Molt4 cells were cultivated. Each step and the conditions of the FLOW-FISH procedure were optimized, standardized and validated. The relative TL (RTL) of the leukemic sample cells compared to the control cells(Molt4).BM samples were derived from 34 leukemia patients. 20 normal PB samples from healthy individuals were set as control group.The BM or PB MNC were collected and used for FLOW-FISH. Meanwhile, the RQ-PCR measurements in the same samples were performed to test the correlation of the two methods.Results:Using various cell lines, multicolor FLOW-FISH was also successfully established.The median of RTL in 24 AL patients was 0.240, 2 CLL was 0.235, 3 CML-BP was 0.249, 5 CML-CP was 0.435, while that in 20 normal controls was 0.408.(P=0.001). The TL was shorter in patients with AL, CLL, CML-BP than in normal controls, otherwise, the CML-CP cases had no difference with the controls. 14 AL patients had the significantly longer telomere with clinical remissions than at impetus stage (P=0.01), and no significant difference was found between the 12 cases with clinical remissions and the normal controls(P=0.363). A high degree of correlation between the RTL obtained from FLOW-FISH and TL estimation by RQ-PCR existed (P=0.000).There was a significant negative correlation between TL and age in 20 normal controls(P=0.001), and the female had longer telomere than the male(P=0.037). However no statistic difference between TL and age or gender existed in 34 de novo leukemia patients. The TL of 24 AL cases had a negative correlation with peripheral white cells counts(P=0.002). Within 23 follow-up AL patients, the CR rate in cases with TL above the median was 81.82%, and 58.23% in the rest. Among 5 CML-CP patients who received imatinib treatment, 2 cases with the shorter telomere occurred transformation to BP in less than 6 months, the other 3 cases obtained CHR within 3 months, CCyR at 6 months and no transformation to BP was observed in our follow-up of 10 months.14 AL patients who undergone simultaneous analysis of TL and immunophenotype show the coincidence with the convention immunology in cell differentiation antigen expression. TL combined with cell differentiation antigen of 5 cases were dynamically detected at different courses of disease. It showed that TL of 2 cases with continued CR restored after CR and remained at normal level during remission, and no specific antigen expressed highly. However, telomere of 3 relapsed cases were significantly shortened at impetus stage, prolonged after CR and shortened again after relapse. In 2 relapsed cases, the telomere of related antigen positive cells shortened before the whole cells, and ahead of cell morphology change.Conclusions:The TL was significantly shorter in 34 de novo leukemia patients than in normal controls except the CML-CP cases. Restored telomeres were found with clinical remissions in 14 AL cases. The two methods of FLOW-FISH and RQ-PCR generated the same results and showed notable correlated.There was a significant negative correlation between TL and age in normal controls, and the female had longer telomere than the male. However no statistic difference between TL and age or gender existed in de novo leukemia patients. The TL of 24 AL cases had a negative correlation with peripheral white cells counts. It seemed the shorter telomere mean the lower CR rates in 23 follow-up cases with AL and the shorter duration of CP before onset of BP in 5 cases with CML.Simultaneous analysis of TL and cell differentiation antigen by multicolor FLOW-FISH made for overall monitor for leukemia and might be a new generally applied method for monitoring MRD in leukemia.

Incidence, temporal trends and potential risk factors for aseptic loosening following primary unicompartmental knee arthroplasty: A meta-analysis of 96,294 knees

BackgroundAseptic loosening (AL) is among the major reasons for revision of failed primary unicompartmental knee arthroplasty (UKA). There is an ongoing temporal increase in the use of UKA with a resultant increase in the revision burden. We aimed to evaluate the incidence of, temporal trends and risk factors for AL. MethodsLongitudinal studies reporting the incidence of AL following primary UKA were sought from MEDLINE, Embase, Web of Science and Cochrane Library up to 6th April 2020. Incidence and relative risks (RR) (with 95% confidence intervals) were calculated. ResultsWe identified 62 studies for inclusion. Overall, 96,294 primary UKA procedures accounting for 1752 AL cases were included. AL incidence ranged from 0.00% to 22.70% over a 7.7 year weighted mean follow-up. The pooled random effects incidence (95% CI) was 1.77% (1.34–2.25) in the same follow-up period. The annual rate of AL was 0.10% (0.02–0.22). AL incidence increased with length of follow-up, but there was a temporal decrease from the 1970s onwards. Tibial loosening was more common than femoral component loosening: incidence (95% CI) of 1.63% (0.96–2.44) and 0.58% (0.20–1.09) respectively over a weighted follow-up of 6.6 years. Fixed bearing implant design and cemented fixation were both associated with increased AL risk, whereas robotic-assisted surgery was associated with decreased risk. ConclusionThe overall incidence of AL following primary UKA is primarily driven by tibial component loosening and there is a temporal decline in rates. The use of mobile bearing, uncemented implants inserted with robotic assisted surgery may reduce the risk of AL.

Novel Optineurin Frameshift Insertion in a Family With Frontotemporal Dementia and Parkinsonism Without Amyotrophic Lateral Sclerosis.

Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), granulin precursor (GRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with four members harboring a novel frameshift insertion at OPTN (Chr 10:13166090 G>GA) p.Lys328GluTer11, three of whom presented with FTD-related phenotypes. Additionally, one sibling heterozygous for the frameshift insertion had a predominantly parkinsonian phenotype resembling corticobasal syndrome, but it remains to be determined if this phenotype is related to the frameshift insertion. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.

A novel splice site FUS mutation in a familial ALS case: effects on protein expression

Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 − 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA analysis revealed the skipping of exon 15 and a premature stop codon at c.228. RT-PCR showed reduced FUS mRNA by more than half compared to a healthy control (HC) and an ALS patient without genetic mutations (wtALS). In WI FUS band intensity in the proband was 30–50% compared to HC and wtALS. An antibody expected to detect only the wild-type protein did not reveal any reduction of FUS band intensity compared to the other antibodies. IF showed no difference among HC, wtALS, and the proband. Discussion: The reduction of FUS mRNA and protein in PBMC suggests the absence of the truncated protein, probably due to nonsense-mediated decay, leading to loss of function.

Recruitment of population-based controls for ALS cases from the National ALS Registry

Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases (n = 280). Here we report our recruitment methods for controls and the associated response rates and costs. Methods: Eligible ALS cases had complete risk factor survey data, DNA analysis, and blood concentrations of persistent organic pollutants (POPs). Age, sex, and county-matched controls were identified from commercial/consumer databases using a targeted landline phone sample. Eligible controls were consented, surveyed, and mailed the POPs’ blood analysis consent form. Once consented, phlebotomy was scheduled. Results: We mailed 3760 recruitment letters for 181 potential case-matches across 42 states between 9/2018 and 3/2020. After making phone contact and determining eligibility, 146 controls agreed to participate (response rate = 11.4%, cooperation rate = 22.8%). To date, 127 controls completed the survey and bloodwork. Though controls were matched to cases on age, sex, and county, unmatched characteristics (e.g. smoking) did not differ statistically. Interviewing and incentive costs are estimated at $211.85 per complete participation. Conclusions: Recruiting matched population-based controls for comparison to cases from the Registry for a study involving completion of a detailed survey and blood specimen provision is relatively feasible and cost effective. This recruitment method could be useful for case-control studies of other rare disorders.

Northeast ALS Consortium National COVID-19 ALS Case Rate Census Survey – 2nd Qtr 2020 (4861)

Northeast ALS Consortium National COVID-19 ALS Case Rate Census Survey – 2nd Qtr 2020 (4861)

Subclinical upper motor neuron involvement at the diagnosis may predict disease progression in a cohort of lower motor neuron syndromes from Southern Italy

BackgroundOnly few epidemiological studies on survival of Lower Motor Neuron (LMN) phenotype (LMNP) are available and with controversial results. AimsTo prospectively evaluate a cohort of LMNP patients and assess the possible contribute on survival or disease's progression according to the presence of subclinical Upper Motor Neuron (UMN) impairment at the diagnosis. MethodsForty LMNP among 176 consecutive incident ALS cases observed in our tertiary center from the ALS-Apulia Register were enrolled in the study. Each patient underwent to a neurophysiological study with transcranial magnetic stimulation (TMS) at diagnosis. The primary outcome was the impact of abnormalities at TMS on survival time (from symptoms onset or diagnosis to death, tracheostomy or 30 June 2020, as censoring time). Secondary outcome was time to reach the King's 4 stage. ResultsApproximately one half of LMNP reached the primary outcome during the study period. No difference was found in median survival times and 4 years survival rates according to the presence of TMS impairment. On the other hand, a shorter median time to reach the King's 4 from onset was observed in the group of LMNP with TMS abnormalities (16 months versus 50 months; p = 0.008). Consistently, TMS abnormalities were associated with a 3.5 times higher risk for reaching King's 4 stage (Hazard Ratio: 3.5; 95% Confidence Interval: 1.1–10.9; p = 0.03). ConclusionOur data suggest a role of TMS abnormalities as potential indicator of disease progression and multidistrectual involvement in patients with pure clinical LMN phenotype at the diagnosis.

The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment

We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500–526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2–27, 400–450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.

Clinicopathological Evaluation of Acute Leukemias in a Tertiary Care Hospital: A Cross-Sectional Study.

Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are clinically and biologically diverse phenotypic diseases amongst hematological malignancies. The current study objectives were to diagnose and classify cases of AL as per revised 4th edition of WHO 2016 classification of AL's and study their clinicopathological profiles. This cross-sectional, observational study included 68 patients, diagnosed with AL were recruited. Diagnosis was based on peripheral blood smear examination, bone marrow aspiration, flowcytometry, and cytogenetic and molecular studies. Sixty-eight cases of AL were diagnosed in a period of 2 years, where 25 cases were of ALL and 43 cases were of AML. In the subclassification of AML as per WHO 2016, 20 cases were of AML, RGA, 21 cases were of AML, NOS, and 2 cases were of AML, MRC. In AML, RGA, APL with PML-RARA positive cases were 10 out of 20 cases, AML with (8;21) RUNX1-RUNX1T1 were 7/20 cases; there were two cases of AML with mutated NPM1 gene and one case of AML with biallelic mutation of CEBPA. In AML, NOS subcategory AML with maturation was more common with 9/21cases. In subcategory of ALL, B-ALL was more common than T-ALL. B-ALL, NOS was more common than B-ALL, RGA and we had 1 case of NK cell Leukemia. The application of revised 4th edition WHO 2016 classification confers uniformity in reporting acute leukemia cases that aids in the treatment by using targeted therapies and helps in the prediction of prognosis. The WHO classification for acute leukemias is very objective, therapy oriented and the need of the hour.

Strategy to Avoid Anastomotic Leakage in Laparoscopic Colorectal Resection Using the Indocyanine Green Fluorescence System

Purpose Anastomotic leakage (AL) in colorectal resections is often caused by insufficient blood flow to the stump. Injecting indocyanine green can help detect blood flow intraoperatively. In this study, we evaluated our original strategy using an indocyanine green fluorescence system to avoid AL. Methods We retrospectively evaluated 79 patients who underwent laparoscopic colorectal resection for colon cancer using a double-stapling technique. Blood flow in oral stumps was evaluated by measuring indocyanine green fluorescence time (FT). We investigated AL cases in detail and analyzed correlations between FT and risk factors for AL. Results Of the 79 patients, 7 (8.9%) developed AL. We divided patients by FTs: &amp;gt;60 seconds, 50 to 60 seconds, and &amp;lt;50 seconds. The AL rates were FT &amp;gt;60 seconds, 60%; FT 50 to 60 seconds, 10.3%; and FT &amp;lt;50 seconds, 2.2%. The AL rate of high-risk cases (with more than 2 risk factors) were calculated and we made our original strategy to avoid AL as the following. Further resection or diverting stomas were needed by the FT &amp;gt;60 seconds group, and by members of the FT 50 to 60 seconds group with ≥3 risk factors. The FT &amp;lt;60 seconds group needed no additional management. Conclusions Patients with delayed FT (&amp;gt;60 seconds, or 50–60 seconds with ≥3 risk factors) may need revision of the anastomosis (diverting stoma or additional resection) to avoid AL. Our original strategy may contribute to reduce AL in colorectal operations.

The Importance of Diagnostic and Prognostic Biomarker Identification and Classification Towards Understanding ALS Pathogenesis.

ALS is increasingly perceived as a multisystem neurodegenerative disorder, and the identification of a panel of biomarkers that accurately reflect features of pathology is a priority, not only for diagnostic purposes but also for prognostic or predictive applications [1]. Thus, as a multisystemic disease, it is likely that a panel of biomarkers will be needed to fully capture the features of ALS pathology. Taking also into consideration the fact that its causes remain unknown to their majority, it remains a complex disease driven by a combination of several systemic parameters [2]. Beyond the monogenic causes, representing the 15% of the ALS cases, which list up to 30 gene mutations with the most frequent being C9orf72, SOD1, FUS, and TARDBP/TDP43 [3-5], much research is being done to identify and associate possible causes for the 80% of ALS cases (sALS and fALS combined) which at the moment are not explained by a known mutation [2, 4]. ALS sporadic cases are related to a multigenic component, and/or involve epigenetic modification, and/or result from DNA damage, environmental risk factors, behavioural factors, oxidative stress or viral infections leading to cellular dysfunctions [4, 6-10]. ALS diagnosis is lengthy and there is a typical diagnostic delay of 9-15months from onset to diagnostic confirmation based on clinical and electrophysiological criteria as well as the exclusion of diseases with similar behaviour to ALS. Three major exclusion criteria are involved in the diagnosis process: the Revised El Escorial Criteria (REEC), the Airlie House Criteria (AHC) and the Awaji Criteria [11, 12]. Taking into consideration that the average survival is 2-4years, it makes it urgent for the researchers to improve diagnostic speed and accuracy for ALS [13, 14]. In the absence of a reliable diagnostic test for ALS, biomarkers are a strong weapon not only for its diagnosis but also for understanding the pathomechanism as well as a basis for the development of therapeutics. Recent global research has accepted the fact that biomarkers will facilitate the combination of therapeutics with diagnostics and will thus play an important role in the development of personalized medicine [15]. This paper proposes a combination of diagnostic and prognostic biomarkers to meet the scope of global research. Thus, biomarkers specific to ALS pathology need to be identified towards the development of a reliable fast diagnostic test, while at the same time prognostic biomarkers should also be identified to monitor the status of the pathology as various candidates may serve both purposes. Finally, since different sub-cohorts of ALS patients respond differently to treatments [16], the identification of ALS biomarkers will contribute to a better understanding of the disease pathogenesis and permit targeted drug development and patient stratification leading to more efficient clinical trials.