Tag: pubmed

Cerebellum. 2022 Aug 20. doi: 10.1007/s12311-022-01458-5. Online ahead of print.

ABSTRACT

To the best of our knowledge, this is the first case to address episodic ataxia (EA) as a possible phenotypic feature of HECW2-related disorder. This single case study describes a 26-year-old female born at term with mild intellectual disability, neonatal hypotonia, and a history of febrile seizures who presented with paroxysmal events since the age of 2. These episodes include frequent falls due to imbalance, dilated pupils, vertigo, diaphoresis, nausea, vomiting, and nystagmus. Brain imaging was normal. A prolonged electroencephalogram (EEG) revealed interictal epileptiform discharges but failed to capture her clinical events. For several years, she was treated for presumed focal seizures with preserved awareness and trialed on adequate dosing of several antiepileptic medications without improvement. After 25 years, given the more prolonged nature of her episodes and the mild interictal cerebellar signs, empiric treatment with acetazolamide was initiated for a presumed diagnosis of EA. Acetazolamide treatment led to a dramatic reduction in event frequency and severity. The initial EA genetic panel was negative. Clinical exome sequence analysis revealed a novel pathogenic de novo missense variant in the HECW2 gene [c.3829 T > C;(p.Tyr1277His)], located in the HECT domain. HECW2 variants are associated with neurodevelopmental delay, hypotonia, and epilepsy. This study expands the genetic and clinical spectrum of HECW2-related disorder and adds EA to the phenotypic spectrum in affected individuals.

PMID:35987951 | DOI:10.1007/s12311-022-01458-5

J Neurooncol. 2022 Aug 20. doi: 10.1007/s11060-022-04116-2. Online ahead of print.

ABSTRACT

PURPOSE: Children diagnosed with craniopharyngioma are vulnerable to adverse health outcomes. Characterization of body mass index (BMI), physical function, and cardiopulmonary fitness in those treated with proton radiotherapy (PRT) will serve to design interventions to improve outcomes.

METHODS: Ninety-four children with craniopharyngioma completed physical function testing prior to PRT and annually for 5 years. For each outcome, age- and sex-specific z-scores were calculated using normative values. Participants with z-scores > 1.5 or < – 1.5 were classified as impaired. Those with z-scores > 2.0 or < – 2.0 were classified as significantly impaired. Descriptive statistics were used to describe study outcomes and change in prevalence of impairments from 2 to 5 years after treatment.

RESULTS: Nearly half of participants [45.2%, 95% confidence interval (CI) 39.4, 51.0] had mean BMI z-scores > 1.5 at baseline, with prevalence increasing to 66.7% (95% CI 61.5, 71.9) at 5 years. More than half of participants (54.2%, 95% CI 48.4, 60.0) had knee extension strength z-scores < – 1.5 at baseline, with prevalence increasing to 81.3% (95% CI 77.7, 84.9) at 5 years. BMI and knee extension strength had the largest proportion of participants impaired at both 2 and 5 years (53.2% and 62.3%, respectively). Resting heart rate had the highest proportion of participants not impaired at 2 years but became impaired at 5 years (26.6%).

CONCLUSIONS: Children with craniopharyngioma have BMI and fitness abnormalities at diagnosis and continue 5 years after treatment. This cohort may benefit from interventions designed to improve BMI, strength, and resting indicators of cardiopulmonary fitness.

PMID:35987949 | DOI:10.1007/s11060-022-04116-2

Ann Biomed Eng. 2022 Aug 20. doi: 10.1007/s10439-022-03046-4. Online ahead of print.

ABSTRACT

Frequently, biomedical researchers need to choose between multiple candidate statistical models. Several techniques exist to facilitate statistical model selection including adjusted R², hypothesis testing and p-values, and information criteria among others. One particularly useful approach that has been slow to permeate the biomedical literature is the notion of posterior model probabilities. A major advantage of posterior model probabilities is that they quantify uncertainty in model selection by providing a direct, probabilistic comparison among competing models as to which is the “true” model that generated the observed data. Additionally, posterior model probabilities can be used to compute posterior inclusion probabilities which quantify the probability that individual predictors in a model are associated with the outcome in the context of all models considered given the observed data. Posterior model probabilities are typically derived from Bayesian statistical approaches which require specialized training to implement, but in this paper we describe an easy-to-compute version of posterior model probabilities and inclusion probabilities that rely on the readily-available Bayesian information criterion. We illustrate the utility of posterior model probabilities and inclusion probabilities by re-analyzing data from a published gait study investigating factors that predict required coefficient of friction between the shoe sole and floor while walking.

PMID:35987947 | DOI:10.1007/s10439-022-03046-4

Commun Biol. 2022 Aug 20;5(1):851. doi: 10.1038/s42003-022-03796-w.

ABSTRACT

Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using a statistical framework to decouple transcriptional and post-transcriptional effects in RNA-seq data, we uncover the mRNA stability changes that accompany tumour development and progression. Analysis of 7760 samples across 18 cancer types suggests that mRNA stability changes are ~30% as frequent as transcriptional events, highlighting their widespread role in shaping the tumour transcriptome. Dysregulation of programs associated with >80 RNA-binding proteins (RBPs) and microRNAs (miRNAs) drive these changes, including multi-cancer inactivation of RBFOX and miR-29 families. Phenotypic activation or inhibition of RBFOX1 highlights its role in calcium signaling dysregulation, while modulation of miR-29 shows its impact on extracellular matrix organization and stemness genes. Overall, our study underlines the integral role of mRNA stability in shaping the cancer transcriptome, and provides a resource for systematic interrogation of cancer-associated stability pathways.

PMID:35987939 | DOI:10.1038/s42003-022-03796-w

Drugs R D. 2022 Aug 20. doi: 10.1007/s40268-022-00399-y. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Irinotecan sometimes causes lethal septic shock but the risk factors remain unclear. This retrospective case-control study explored the potential risk factors for septic shock following irinotecan treatment.

METHODS: All women who received irinotecan-containing chemotherapy for gynecologic malignancies at Shizuoka General Hospital from October 2014 to September 2020 were investigated. The clinical backgrounds and blood test results of those who developed septic shock after irinotecan-containing chemotherapy were compared with those who did not. Odds ratios (ORs) for developing septic shock after receiving irinotecan were calculated with 95% confidence intervals (CIs), using univariable logistic regression analysis.

RESULTS: During the study period, 147 women received irinotecan-containing chemotherapy. Three women developed septic shock due to neutropenic enterocolitis after irinotecan treatment, and 144 did not. The three patients with septic shock had recurrent cervical cancer, heterozygous variants in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene (two patients had *1/*6, one had *1/*28 variants), a history of concurrent chemoradiation therapy, 50-60 Gy of pelvic irradiation, and platinum-combined chemotherapy. A history of pelvic irradiation was identified as a possible risk factor for developing septic shock after irinotecan-containing chemotherapy (OR 63.0, 95% CI 5.71-8635; p < 0.001). The OR of UGT1A1 polymorphism for septic shock was 9.09 (95% CI 0.86-1233; p = 0.070) in the complete case analysis.

CONCLUSION: Medical personnel involved in cancer therapy should consider the possible risk of septic shock developing due to neutropenic enterocolitis when administering irinotecan-containing chemotherapy in patients with a history of pelvic irradiation.

PMID:35987938 | DOI:10.1007/s40268-022-00399-y

J Cancer Res Clin Oncol. 2022 Aug 20. doi: 10.1007/s00432-022-04184-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard treatment for younger patients with newly diagnosed multiple myeloma (MM). However, due to restrictive exclusion criteria, more than half of eligible patients are usually excluded from transplant studies.

METHODS: This retrospective monocentric analysis included 540 patients with MM who received an ASCT between 1996 and 2019.

RESULTS: Up to 2005, induction therapy consisted mainly of conventional chemotherapies, e.g. vincristine/doxorubicin/dexamethasone (VAD). In the following years, the triple-combinations based on bortezomib coupled with doxorubicin/dexamethasone (PAD), melphalan/prednisolone (VMP), cyclophposphamide/dexamethasone (VCD) or bendamustine/prednisolone (BPV) became the most popular treatment options. A progressive improvement in PFS was observed in patients treated with the two current induction therapies BPV (47 months) or VCD (54 months) compared to VAD (35 months, p < 0.03), PAD (39 months, p < 0.01 and VMP (36 months, p < 0.01). However, there was no significant difference in median OS (VAD 78, PAD 74, VMP 72, BPV 80 months and VCD not reached). In our analysis, we also included 139 patients who do fulfill at least one of the exclusion criteria for most phase 3 transplant studies (POEMS/amyloidosis/plasma cell leukemia, eGFR < 40 mL/min, severe cardiac dysfunction or poor general condition). Outcome for these patients was not significantly inferior compared to patients who met the inclusion criteria for most of the transplant studies with PFS of 36 vs 41 months (p = 0.78) and OS of 78 vs 79 months (p = 0.34).

CONCLUSIONS: Our real-world data in unselected pts also stress the substantial value of ASCT during the first-line treatment of younger MM pts.

PMID:35987926 | DOI:10.1007/s00432-022-04184-x

Bone Marrow Transplant. 2022 Aug 20. doi: 10.1038/s41409-022-01770-y. Online ahead of print.

ABSTRACT

HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) and umbilical cord blood transplantation (UCBT) are alternative to HLA-matched stem cell transplantation. We conducted a matched-pair analysis of PTCy-haplo and UCBT using the Japanese registry data. We identified 136 patients aged between 16 and 69 years who received PTCy-haplo as their first transplantation for acute leukemia or myelodysplastic syndromes. Control group included 408 UCBT recipients selected to match the PTCy-haplo group. Overall and relapse-free survival probabilities at 2 years were comparable between the PTCy-haplo and UCBT groups: 55% vs. 53% for overall survival (p = 0.46), and 47% vs. 48% for relapse-free survival (p = 0.79), respectively. The cumulative incidence of relapse was significantly higher (43% vs. 29%, respectively, p = 0.006), while the cumulative incidence of non-relapse mortality (NRM) was significantly lower (9% vs. 23%, respectively, p < 0.001) in the PTCy-haplo group. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was lower in the PTCy-haplo group compared to the UCBT group (29% vs. 41%, respectively, p = 0.016), while those of grade III-IV acute GVHD and chronic GVHD were not statistically different between the two groups. Our results suggest that both PTCy-haplo and UCBT are viable alternatives to HLA-matched stem cell transplantation.

PMID:35987912 | DOI:10.1038/s41409-022-01770-y

Am J Cardiol. 2022 Aug 17:S0002-9149(22)00715-9. doi: 10.1016/j.amjcard.2022.06.032. Online ahead of print.

ABSTRACT

In the absence of risk factors like bicuspid aortic valve, connective tissue disorder, or family history of aortic dissections, degenerative thoracic aortic aneurysm appears to be an indolent disease. Most American and European societies recommend yearly or biannual imaging of the thoracic aorta with computed tomographic (CT) imaging, magnetic resonance (MRI) imaging, and transthoracic echocardiographic (TTE) examination. We aimed to identify the rate of progression and predictors of early degenerative aortic root dilatation (ARD) and ascending aortic dilatation (AAD) over a period of 10 years on the basis of echocardiographic measurements. A retrospective chart analysis was performed on 340 patients (mean age 67.4 ± 11.6 years; 85.6% men; 83.8% White) with known ARD and AAD. Aortic root and ascending aorta measurements were followed by serial echocardiograms from the time of the first diagnosis for a total of 10 years. During this time, the mean change in ARD was 0.28 ± 0.71 mm and AAD was 0.15 ± 0.18 mm. On multivariate regression after adjusting for baseline demographics, risk factors, and medication use, there was no statistically significant increase in their unit change in mean ARD or AAD. In conclusion, mild to moderate degenerative thoracic aortic aneurysm has a minimal change in dimensions over time, and current guidelines recommending yearly surveillance imaging of ARD and AAD need to be revisited to allow a more liberal follow-up interval.

PMID:35987908 | DOI:10.1016/j.amjcard.2022.06.032

J Cardiothorac Surg. 2022 Aug 20;17(1):194. doi: 10.1186/s13019-022-01940-5.

ABSTRACT

OBJECTIVE: To evaluate the serum D-dimer level and its diagnostic and prognostic predictive value in patients with different types of aortic dissection.

METHODS: Eighty-four aortic dissection patients who were diagnosed clinically in our hospital from January 2017 to January 2021 were selected for the study. All patients were divided into Stanford type A (39 cases) and Stanford type B (45 cases) groups. The serum D-dimer level was detected at 1 h, 6 h, 12 h, 24 h, and 72 h after admission to the hospital, and its expression level with different types of aortic dissection was analyzed. The relationship between D-dimer and the prognosis of patients was also analyzed.

RESULTS: The serum D-dimer levels of patients in group A were significantly higher than those in group B at 6 h, 12 h, 24 h, and 72 h after admission, and the differences were statistically significant. In group A, 16 patients died, and 23 patients survived, while in group B, 18 patients died, and 27 patients survived. The serum D-dimer level of the dead and surviving patients in group A was significantly higher than that of group B, and the serum D-dimer level of dead patients in groups A and B was significantly higher than that of surviving patients. For diagnostic value, the AUC was 0.89, sensitivity was 76.92%, specificity was 90.00% in group A, and the AUC was 0.82, sensitivity was 71.11%, and specificity was 85.00% in group B. For the prognostic predicted value, the AUC was 0.74 in group A, while the AUC was 0.69 in group B.

CONCLUSIONS: D-dimer has different serum levels in different types of aortic dissection patients, with higher levels in Stanford A. Serum D-dimer levels may be used as a better biomarker to diagnose the two types of aortic dissection and play an important role in patient prognostic prediction, especially Stanford type A.

PMID:35987892 | DOI:10.1186/s13019-022-01940-5

Eur Geriatr Med. 2022 Aug 20. doi: 10.1007/s41999-022-00686-6. Online ahead of print.

ABSTRACT

PURPOSE: Frailty is a common clinical syndrome affecting hip fracture patients. Recognising and accurately assessing frailty status is important in clinical and research settings. The Rockwood Clinical Frailty Scale (CFS) is a commonly used instrument and demonstrates a strong correlation with mortality and length of hospital admission following hip fracture. What is not understood, however, is the validity of retrospectively assigned CFS scores in hip fracture patients. The aim of this study was to assess the validity of retrospective non-orthogeriatrician assigned CFS scores in hip fracture patients.

METHODS: Hip fracture patients from a single major trauma centre were assessed and CFS scores were assigned prospectively by non-orthogeriatric clinicians (n = 57). A subset of these patients were also assigned a prospective CFS score by a specialist orthogeriatrician (n = 27). Two separate blinded observers (non-orthogeriatric clinicians) assigned CFS scores retrospectively using electronic patient records alone. Agreement and precision was examined using the Bland-Altman plot, accuracy was assessed using R² statistic and inter-rater reliability was assessed using quadratic weighted Cohen’s kappa.

RESULTS: Seventy percent of the cohort were female with an average age of 83. Agreement was high between prospective non-orthogeriatrician assigned CFS scores and retrospective non-orthogeriatrician assigned CFS scores, with a low bias (0.046) and good accuracy (R² = 73%). Good agreement was also seen in comparisons between prospective orthogeriatrician assigned CFS scores versus retrospective non-orthogeriatrician assigned scores, with a low bias (0.23) and good accuracy (R² = 78%). Good inter-rater reliability was seen between blinded observers with a quadratic weighted Cohen’s kappa of 0.76.

CONCLUSIONS: Retrospective CFS scores assigned by non-orthogeriatricians are a valid means of assessing frailty status in hip fracture patients. However, our results suggest a tendency for non-orthogeriatricians to marginally overestimate frailty status when assigning CFS scores retrospectively.

PMID:35987870 | DOI:10.1007/s41999-022-00686-6