Radiologically Inserted Gastrostomy Tube Placement Guided by the Assessment and Primary Palliative Care Provided by an Amyotrophic Lateral Sclerosis Multidisciplinary Clinic: A Single-Arm Retrospective Clinical Study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a median survival of about 3 years. An ALS multidisciplinary team can provide primary palliative care and improve outcomes and quality of life for patients. Feeding tube insertion may be considered for patients with significant weight loss, or respiratory insufficiency. While radiologically inserted gastrostomy (RIG) tube placement may be an option, further studies are required to determine its best timing and appropriateness. This study's objectives were to evaluate the feasibility and outcomes of RIG tube placement in ALS patients over a 90-day follow-up period through the assessment and primary palliative care provided by the multidisciplinary team. This retrospective study reviewed the placement of 16 or 18 French RIG-tube without intubation or endoscopy for 36 ALS patients at a single center between April 2019 and December 2021. Measures included ALS Functional Rating Scale-Revised (ALSFRS-R) scores to determine the ALS stage. Demographic, clinical, procedural, and follow-up data were reviewed. Results showed that the RIG tube placement had a low rate of minor adverse events (11%) and no major procedure-related adverse events. The mean ALSFRS-R score at the time of procedure in subjects who died within 90 days was lower than of those alive beyond 90 days (P = .04). This study found that RIG-tube placement is a safe and effective way to manage dysphagia in ALS patients and highlights the importance of educating members of the multidisciplinary clinic in palliative care principles to determine the appropriateness of RIG tube placement.

Clinical and electrophysiological findings in C9ORF72 ALS.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disorder of motor neurons in which the cause is mostly unknown. Early identification of genetic ALS cases, of which C9ORF72 (C9ALS) is the most frequent, can have important implications for evaluation, prognosis, and therapeutics. Here, we aimed to characterize the clinical and electrophysiological hallmarks of C9ALS and investigate differences from C9ORF72 negative ALS (non-C9ALS). METHODS: We retrospectively reviewed clinical and electrodiagnostic (EDX) data for all genetically confirmed C9ALS cases seen between 1/1/2012 and 10/1/2020 who met Gold Coast criteria and compared them 1:1 with non-C9ALS patients within the same time frame. RESULTS: A total of 99 C9ALS and 99 non-C9ALS cases were identified. Compared to non-C9ALS, C9ALS demonstrated higher prevalence in women, lesser racial variability, stronger family history of ALS, and higher frequency of upper motor neuron signs. EDX testing of C9ALS showed higher median sensory nerve and lower fibular compound muscle action potential amplitudes. DISCUSSION: Although the differences between C9ALS and non-C9ALS reached statistical significance in certain nerve conduction parameters, they were not sufficient to discriminate between groups on a case-by-case basis. Genetic testing is required to identify C9ALS patients.

Comparative Performance of Different Respiratory Test Parameters for Detection of Early Respiratory Insufficiency in Patients With ALS.

BACKGROUND AND OBJECTIVES: To compare the performance of different respiratory function testing parameters in a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic. METHODS: Demographics, clinical data, and respiratory testing parameters were abstracted from the medical records of patients who attended a multidisciplinary ALS clinic from 2008 to 2016. We compared the performance of the 3 primary respiratory test parameters used by Medicare for the initiation of noninvasive ventilation (NIV) (forced vital capacity [FVC] < 50% predicted, maximum inspiratory pressure [MIP] < 60 cm H2O, and abnormal overnight pulse oximetry [OvOx]) on how they related to several clinically relevant attributes. RESULTS: Four hundred seventy-six patients were identified who underwent at least 1 respiratory test. Abnormalities of OvOx, MIP, and FVC occurred at a median of 1.6, 1.5, and 3.8 years from disease onset, respectively (p < 0.00001). Patients with bulbar-onset ALS exhibited earlier abnormalities in MIP and FVC than in spinal-onset ALS (p < 0.005). The median survival after an abnormal OvOx, MIP, or FVC test was 1.4, 1.4, and 0.9 years, respectively (p < 0.0001). Using the ALS Functional Rating Score respiratory subscales, at the time of reported respiratory symptoms there were abnormalities in OvOx (60%), MIP (69%), and FVC (19%). Conversely, when respiratory parameter abnormalities preceded reported respiratory symptoms, this occurred with frequencies in OvOx (79%), MIP (42%), or FVC (24%). Four hundred forty-three patients (93.1%) developed at least 1 abnormal respiratory measure meeting Medicare criteria for NIV consideration, but fewer than 50% in our cohort demonstrated NIV use. Improved survival in subjects using NIV was statistically significant in patients with bulbar-onset ALS. DISCUSSION: Abnormalities in OvOx and MIP perform better than FVC at early detection of neuromuscular respiratory weakness in ALS. Initiation of NIV in patients with respiratory insufficiency may improve the overall survival in ALS. In the setting of the COVID-19 pandemic, FVC and MIP have not been routinely performed because of infectious aerosol generation. OvOx, which we now routinely mail to patients' homes, has been used exclusively during the COVID-19 pandemic and allows for continued remote monitoring of the respiratory status of patients with ALS. CLASSIFICATION OF EVIDENCE: This cohort study provides Class III evidence that in people with ALS, OvOx and MIP are valuable respiratory parameters for the detection of early respiratory insufficiency.

Prevalence of Gastrointestinal Symptoms, Severity of Dysphagia, and Their Correlation with Severity of Amyotrophic Lateral Sclerosis in a Mexican Cohort.

OBJECTIVES: Our study aimed to identify the prevalence and severity of gastrointestinal (GI) symptoms and dysphagia in patients with amyotrophic lateral sclerosis (ALS) and to assess whether a correlation exists between these symptoms and the severity of ALS progression. METHODS: The presence and severity of GI symptoms and dysphagia were identified by means of the Gastrointestinal Symptom Rating Scale (GSRS) and the Functional Outcome Swallowing Scale (FOSS). The Revised ALS Functional Rating Scale (ALSFRS-R) was utilized to determine the severity of ALS. Analysis of data was performed with Spearman correlations in semi-qualitative variables of clinical scales. ALSFRS-R scores were divided into 2 categories: those with mild to moderate ALS (≥40-30 points) and patients with moderate to advanced ALS (29-≤20 points). RESULTS: We studied 43 patients with definite ALS. The most frequent GI symptoms were constipation (60.5%), rectal tenesmus (57.5%), hard stools (55.0%), and borborygmus (42.5%). The moderate to advanced ALS stage was correlated with constipation (r = 0.334; p = 0.028), acid regurgitation (r = 0.384; p = 0.013), eructation (r = 0.334; p = 0.032), rectal tenesmus (r = 0.498; p = 0.001), and functional dysphagia (r = 0.656; p = <0.001). CONCLUSIONS: Early detection of these GI symptoms can guide timely therapeutic decisions to avoid weight loss, a predictor for worse prognosis. This study highlights the relevance of the detection of these symptoms in ALS patients who score ≤29 points in the ALSFRS-R scale to establish an appropriate treatment, prevent systemic complications, provide more comfort, and improve quality of life.

3D bioprinting of glioblastoma models.

The most common and malignant primary brain tumor in adults is glioblastoma (GBM). In vitro 3D brain models are needed to better understand the pathological processes underlying GBM and ultimately develop more efficient antineoplastic agents. Here, we describe the bioprinting methods that have been used to fabricate volumetric GBM models. We explain several factors that should be considered for 3D bioprinting, including bioinks, cells and construct designs, in relation to GBM modeling. Although 3D-bioprinted brain models are still to be improved, they have the potential to become a powerful tool for drug screening.

Improving Bioprinted Volumetric Tumor Microenvironments In Vitro.

Despite the great breakthroughs in the past few decades in illuminating the pathological mechanisms of cancer and in developing new anticancer drugs, it remains extremely challenging to cure most cancers. Therefore, it is imperative to develop more sophisticated and more biomimetic preclinical cancer models. 3D models combined with dynamic culture techniques show great potential to accurately emulate the volumetric tumor microenvironment (TME). Here we introduce advances in bioprinting technologies for in vitro cancer modeling and their applications. Finally, we look ahead to the remaining challenges associated with current bioprinting strategies for achieving faithful cancer modeling.

Inferior vena cava filters in pulmonary embolism: A historic controversy / Filtros de vena cava inferior en tromboembolia pulmonar: Una controversia histórica

Abstract: Objective: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. Methods: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. Results: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. Conclusion: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.

Resumen: Objetivo: Racionalidad para no utilizar en forma rutinaria filtros de vena cava inferior (FVCI) en pacientes con tromboembolia pulmonar (TEP). Métodos: Analizamos mecanismos de trombosis relacionados con la colocación o retiro de estos dispositivos médicos, incluyendo la importancia del polifosfato inorgánico en la vía de activación de contacto. Analizamos evidencia clínica de estudios aleatorizados controlados en pacientes con y sin cáncer. Mediante tablas de frecuencia estimamos de cada estudio reducción del riesgo absoluto (RRA) y relativo (RRR) y el número necesario a tratar (NNT). Finalmente, examinamos la evolución de nuestros pacientes con TEP llevados a trombolisis con seguimientos a corto y largo plazo. Resultados: FVCI inducen trombosis por diferentes mecanismos: colocación y retiro, adsorción rápida de proteínas y activación de superficie inducida en la vía de activación de contacto. El polifosfato inorgánico es un procoagulante importante para la anticoagulación. Estudios aleatorizados controlados incluyeron 904 pacientes con TEP con y sin cáncer. En términos de RRA, RRR y NNT no existe evidencia para el uso rutinario. En 290 pacientes con TEP probada, importante carga de trombo y disfunción del ventrículo derecho llevados a trombolisis y anticoagulación observamos una evolución favorable en seguimientos a corto y largo plazo. En estos pacientes los FVCI se utilizaron solo en el 5%. Conclusión: Considerando los mecanismos complejos de trombosis relacionados con los FVCI, la evidencia obtenida de los estudios aleatorizados y controlados, así como la RRA, RRR y NNT en pacientes con tromboembolismo venoso con y sin cáncer, no recomendamos el uso rutinario de FVCI.

Inferior vena cava filters in pulmonary embolism: A historic controversy.

OBJECTIVE: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. METHODS: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. RESULTS: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. CONCLUSION: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.