Nevin Manimala

J Neurosurg. 2022 Sep 9:1-10. doi: 10.3171/2022.7.JNS22314. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the long-term outcomes after resection of brainstem cavernous malformations (BSCMs) and to assess the usefulness of the Lawton grading system in these cases.

METHODS: This retrospective study analyzed 46 consecutive patients with BSCMs operated on between July 1990 and December 2020. Outcomes at the last follow-up were defined as favorable (modified Rankin Scale [mRS] score 0-2) or unfavorable (mRS score > 2).

RESULTS: The study cohort comprised 24 men (52%) and 22 women (48%), ranging in age from 8 to 78 years old (median 37 years). In 19 patients (41%), the preoperative mRS score was > 2. All patients had hemorrhagic BSCM. There were 12 (26%) mesencephalic, 19 (41%) pontine, 7 (15%) medullary, and 8 (17%) cerebellar peduncle lesions, with a maximal diameter ranging from 5 to 40 mm (median 15 mm). In total, 24 BSCMs (52%) had bilateral extension crossing the brainstem midline. Lawton grades of 0, I, II, III, IV, V, and VI were defined in 3 (7%), 2 (4%), 10 (22%), 11 (24%), 8 (17%), 7 (15%), and 5 (11%) cases, respectively. Total resection of BSCMs was attained in 43 patients (93%). There were no perioperative deaths. Excluding the 3 most recent cases, the length of follow-up ranged from 56 to 365 months. The majority of patients demonstrated good functional recovery, but regress of the preexisting oculomotor nerve deficit was usually incomplete. No new hemorrhagic events were noted after total resection of BSCMs. In 42 patients (91%), the mRS score at the time of last follow-up was ≤ 2 (favorable outcome), and in 18 (39%), it was 0 (absence of neurological symptoms). Forty-four patients (96%) demonstrated clinical improvement and 2 (4%) had no changes compared with the preoperative period. Multivariate analysis revealed that only lower Lawton grade had a statistically significant independent association (p = 0.0280) with favorable long-term outcome. The area under the receiver operating characteristic curve for prediction of favorable outcome with 7 available Lawton grades of BSCM was 0.93.

CONCLUSIONS: Resection of hemorrhagic BSCMs by an experienced neurosurgeon may be performed safely and effectively, even in severely disabled patients. In the authors’ experience, preexisting oculomotor nerve palsy represents the main cause of permanent postoperative neurological morbidity. The Lawton grading system effectively predicts long-term outcome after surgery.

PMID:36087317 | DOI:10.3171/2022.7.JNS22314

Eur J Heart Fail. 2022 Sep 10. doi: 10.1002/ejhf.2677. Online ahead of print.

ABSTRACT

AIMS: Empagliflozin reduces cardiovascular death (CVD) or heart failure hospitalization (HHF) in patients with HF and preserved ejection fraction (HFpEF). Treatment effects and safety in relation to resting heart rate (RHR) have not been studied.

METHODS AND RESULTS: The interplay of RHR and empagliflozin effects in EMPEROR-Preserved was evaluated. We grouped patients (n=5988) according to their baseline RHR [<70 bpm (n=2650), 70-75 bpm (n=967), >75 bpm (n=1736)] and explored the influence of RHR on CVD or HHF (primary outcome) and its components in sinus rhythm or atrial fibrillation/flutter (AF) and adverse events. We studied the efficacy of empagliflozin across the RHR spectrum. Compared to placebo, empagliflozin did not change heart rate over time. The primary outcome (p trend = 0.0004) and its components CVD (p trend = 0.0002), first HHF (p trend = 0.0099) and all-cause death (p=0.0001) increased with RHR only in sinus rhythm but not AF. The risk increase with RHR was similar in patients with HFmrEF (LVEF 40-49%) and HFpEF (LVEF >=50%). Baseline RHR had no influence on the effect of empagliflozin on the primary outcomes (p trend = 0.20), first HHF (p trend = 0.49). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the RHR groups.

CONCLUSION: RHR associates with outcomes only in sinus rhythm but not in AF. Empagliflozin reduced outcomes over the entire RHR spectrum without increase of adverse events. This article is protected by copyright. All rights reserved.

PMID:36087309 | DOI:10.1002/ejhf.2677

Int J Gynaecol Obstet. 2022 Sep 10. doi: 10.1002/ijgo.14453. Online ahead of print.

ABSTRACT

AIM: To analyze the effects of substituting the National Diabetes Data Group (NDDG) criteria with the International Association of Diabetes and Pregnancy Study Groups (IADPSG) or American Diabetes Association (ADA) criteria for the diagnosis of early-onset gestational diabetes mellitus (Early-GDM) or first trimester abnormal glucose tolerance (1t-AGT).

METHODS: A retrospective cohort study was conducted of 3200 women: 400 with Early-GDM, 800 with GDM, and 2000 with Non-GDM, according to the NDDG criteria. Rates of women with missed and new Early-GDM according to the IADPSG or ADA criteria were calculated. Multivariate logistic regression analysis was used to compare perinatal outcomes between groups.

RESULTS: Using the IADPSG criteria, 61.6% of women with Early-GDM according to the NDDG were undiagnosed (Missed-Early-GDM group), and 25.9% of women with GDM and 15.7% of women with Non-GDM were diagnosed with Early-GDM (New-Early-GDM groups). Perinatal outcomes were worse in Missed-Early-GDM than in Non-GDM and better in New-Early-GDM groups than in the Early-GDM group. According to the ADA recommendations, only 11.8% of women with Early-GDM according to the NDDG criteria were diagnosed.

CONCLUSION: Replacing the NDDG recommendations for the diagnosis of Early-GDM with the IADPSG or ADA criteria would mean depriving a large number of women with AGT and higher risk of adverse perinatal outcomes from early treatment and treating others with lower risk.

PMID:36087278 | DOI:10.1002/ijgo.14453

J Oral Pathol Med. 2022 Sep;51(8):721-729. doi: 10.1111/jop.13341. Epub 2022 Aug 17.

ABSTRACT

BACKGROUND: Atypical/unbalanced rearrangement in salivary secretory carcinoma was observed and its incidence, patterns, and clinical significance remain unknown.

METHODS: One hundred and ninety-six cases of diagnosed secretory carcinoma were retrospectively reviewed. Fluorescence in situ hybridization for NTRK3/ETV6::NTRK3 was conducted on cases carrying the atypical ETV6 fluorescence in situ hybridization signals. Cases without ETV6::NTRK3 were selected for next-generation sequencing to reveal novel partner. Immunohistochemistry and follow-up were performed.

RESULTS: Twenty-seven cases were confirmed to carry the atypical ETV6 fluorescence in situ hybridization signal patterns. The most common type of abnormality was the duplication of ETV6 5′ end (1Y1GnR, n ≥ 2) with the incidence of 81.5% (22/27). Seventeen of 19 were identified with ETV6::NTRK3 and 2 with ETV6::RET. The immunophenotype was similar to the typical secretory carcinoma group. TrkC exhibited 68.8% sensitivity and 100% specificity for NTRK3 fusion. Microscopically, 5 out of 21 were accompanied by necrosis and 3 out of 21 showed neural invasion. Four out of 19 patients showed local relapse, 2 developed distant metastasis, and 1 died of disease. The patients with distant metastasis and even dead were both harbored ETV6::RET rearrangement. Statistical analysis revealed that there were no significant differences in disease-free survival, relapse-free survival, and distant metastasis-free survival between atypical and typical groups.

CONCLUSION: Gene rearrangement can be identified although the fluorescence in situ hybridization signals were atypical, which was instructive for secretory carcinoma diagnosis in clinical practice. The signals of partners were also always atypical which may have an impact to the efficacy of targeted drugs. There was no statistical evidence that this group possessed worse prognosis. However, secretory carcinomas with ETV6::RET have dismal prognosis than those with ETV6::NTRK3.

PMID:36087274 | DOI:10.1111/jop.13341

Mol Biol Rep. 2022 Sep 10. doi: 10.1007/s11033-022-07707-4. Online ahead of print.

ABSTRACT

BACKGROUND: Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters.

METHODS AND RESULTS: Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal-Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers.

CONCLUSION: We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options.

PMID:36087249 | DOI:10.1007/s11033-022-07707-4

Clin Pharmacol Ther. 2022 Sep 10. doi: 10.1002/cpt.2745. Online ahead of print.

ABSTRACT

High saturated fat diets have been shown to raise blood levels of cholecystokinin (CCK) and induce nonalcoholic steatohepatitis (NASH). CCK receptors are expressed on stellate cells and responsible for hepatic fibrosis when activated. The purpose of this study was to test the safety and dose of a CCK receptor antagonist, proglumide, in human subjects with NASH. An open-labeled single ascending dose study was conducted in 18 subjects with clinical NASH based upon steatosis by liver ultrasound, elevated hepatic transaminases, and a component of the metabolic syndrome. Three separate cohorts (N=6 each) were treated with oral proglumide for 12 weeks in a sequential ascending fashion with 800 (cohort-1), 1200 (cohort-2), and 1600 (cohort-3) mg/day, respectively. Blood hematology, chemistries, proglumide levels, a biomarker panel for fibrosis, and symptom surveys were determined at baseline and every four weeks. Abdominal ultrasounds and transient elastography utilizing FibroScan® were obtained at baseline and at week-12. Proglumide was well tolerated at all doses without any serious adverse events. There was no change in body weight from baseline to week-12. For Cohorts-1, -2, and -3, the median percent change in alanine aminotransferase was 8.42, -5.05, and -22.23 and median percent change in fibrosis score by FibroScan® was 8.13, -5.44, and -28.87 (kPa), respectively. Hepatic steatosis as measured by CAP score significantly decreased with proglumide, (P<0.05). Blood microRNA biomarkers and serum 4-hydroxyproline were consistent with decreased fibrosis at week-12 compared to baseline. These findings suggest proglumide exhibits anti-inflammatory and anti-fibrotic properties and this compound is well tolerated in subjects with NASH.

PMID:36087237 | DOI:10.1002/cpt.2745

Clin Rheumatol. 2022 Sep 10. doi: 10.1007/s10067-022-06370-1. Online ahead of print.

ABSTRACT

OBJECTIVES: Although most of the autoinfammatory disorders have a confirmed genetic cause, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome still has an unknown genetic background. However, familial cases of PFAPA syndrome have been reported suggesting a genetic its basis. PFAPA syndrome may also be considered an infammasome disorder as variants in infammasome-associated genes such as CARD8, NLRP3, and MEFV have been reported to contribute to the disease.

METHODS: Polymerase chain reaction (PCR)/Sanger sequencing analysis was performed for the detection of the variations in 71 PFAPA patients and 71 healthy controls. NLRP3 concentrations in serum were measured in 71 PFAPA patients and 71 healthy controls.

RESULTS: No statistically significant differences were observed in the allele or genotype frequencies of the NLRP3 polymorphisms between the controls and patients (P > 0.05). We found no significant differences for NLRP3 serum levels between PFAPA patients and controls (p > 0.05). Mutations in the MEFV gene were detected in 32.5% of our patients (13/40).

CONCLUSIONS: It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome. For this reason, it may be useful to examine the presence of mutations in genes such as NLRP3, MEFV, and CARD8 together while investigating the genetics of PFAPA syndrome. Key points • Familial cases of PFAPA syndrome have been reported suggesting a genetic basis for this syndrome. • Elevated serum or plasma levels of IL-1β, IL-6, and IL-18 have been demonstrated during PFAPA flares in several studies. • It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome.

PMID:36087224 | DOI:10.1007/s10067-022-06370-1

J Nephrol. 2022 Sep 10. doi: 10.1007/s40620-022-01448-0. Online ahead of print.

ABSTRACT

BACKGROUND: People with kidney failure treated with dialysis are at increased risk of SARS-CoV-2 infection, and severe COVID-19 outcomes such as hospitalization and death. Though there are well-defined sex differences in outcomes for the general population with COVID-19, we do not know whether this translates into kidney failure populations. We aimed to estimate the differences in COVID-19 symptoms and clinical outcomes between males and females treated with maintenance dialysis.

METHODS: In this prospective observational cohort study, we included adults treated with maintenance dialysis in Southern Alberta, Canada that tested positive for COVID-19 between March 2020 and February 2022. We examined the association between sex (dichotomized as male and female) with COVID-19 symptoms including fever, cough, malaise, shortness of breath, muscle joints/aches, nausea and/or vomiting, loss of appetite, diarrhea, headache, sore throat, and loss of smell/taste using chi-square or Fisher’s exact tests. Secondary outcomes included 30-day hospitalization, ICU admission, and death.

RESULTS: Of 1,329 cohort participants, 246 (18.5%) tested positive for SARS-CoV-2 and were included in our study, including 95 females (39%). Of 207 participants with symptoms assessed, females had less frequent fever (p = 0.003), and more nausea or vomiting (p = 0.003) compared to males, after correction for multiple testing. Males exhibited no symptoms 25% of the time, compared with 10% of females (p = 0.01, not significant when corrected for multiple testing). We did not identify statistically significant differences in clinical outcomes between the sexes, though vaccinated patients had lower odds of hospitalization.

CONCLUSIONS: Sex differences in COVID-19 symptoms were identified in a cohort of patients treated with maintenance dialysis, which may inform sex-specific screening strategies in dialysis units. Further work is necessary to examine mechanisms for identified sex differences.

PMID:36087218 | DOI:10.1007/s40620-022-01448-0

Methods Mol Biol. 2022;2574:309-366. doi: 10.1007/978-1-0716-2712-9_16.

ABSTRACT

Paired- and single-chain T cell receptor (TCR) sequencing are now commonly used techniques for interrogating adaptive immune responses. TCRs targeting the same epitope frequently share motifs consisting of critical contact residues. Here we illustrate the key features of tcrdist3, a new Python package for distance-based TCR analysis through a series of three interactive examples. In the first example, we illustrate how tcrdist3 can integrate sequence similarity networks, gene-usage plots, and background-adjusted CDR3 logos to identify TCR sequence features conferring antigen specificity among sets of peptide-MHC-multimer sorted receptors. In the second example, we show how the TCRjoin feature in tcrdist3 can be used to flexibly query receptor sequences of interest against bulk repertoires or libraries of previously annotated TCRs based on matching of similar sequences. In the third example, we show how the TCRdist metric can be leveraged to identify candidate polyclonal receptors under antigenic selection in bulk repertoires based on sequence neighbor enrichment testing, a statistical approach similar to TCRNET and ALICE algorithms, but with added flexibility in how the neighborhood can be defined.

PMID:36087210 | DOI:10.1007/978-1-0716-2712-9_16

Environ Sci Pollut Res Int. 2022 Sep 10. doi: 10.1007/s11356-022-22903-2. Online ahead of print.

ABSTRACT

Global warming in the twenty-first century has gradually made high temperatures a major threat to the global population. Health problems associated with extreme temperatures have become a growing public health concern worldwide. This study aimed to estimate road injuries stratified by sex, age, geographic location, and sociodemographic status attribute to high, low, and non-optimal temperatures in 21 regional and global. We used the Global Burden of Disease (GBD) Study Results Tool to examine the age-standardized death rates (ASDR) and disability-adjusted life years (DALYs) due to road injuries in 2019 by Joinpoint regression. In addition, we reported high, low, and non-optimal temperature exposures for road injuries across different groups by gender, age, region, and disease. Moreover, we examined temporal trends in the burden of road disease caused by high, low, and non-optimum temperatures from 1990 to 2019. Trend analyzes were conducted for five sociodemographic index (SDI) regions. Globally, both ASDR and DALY declined from 1990 to 2019, with average annual percent change (AAPC) values of – 1.3% and – 1.2%, respectively. In 2019, the indicators (death and DALYs) steadily declined, while SDI quintile increased in most regions. Road injuries related to death and DALYs rate attributed to high temperatures were 0.17 and 8.50, respectively, in 2019. From 1990 to 2019, DALYs for road injuries caused by low temperatures showed the most significant upward trend in most regions, especially in low-latitude countries. This study provides a comprehensive understanding of the road injury burden caused by high, low, and non-optimum temperatures, which remains high in regions with low SDI. Therefore, special attention should be paid to road injuries in poor countries or in areas with extreme temperatures.

PMID:36087177 | DOI:10.1007/s11356-022-22903-2