Development and validation of a nomogram for tracheotomy decannulation in individuals in a persistent vegetative state: A multicentre study.

BACKGROUND: Decannulation for people in a persistent vegetative state (PVS) is challenging and relevant predictors of successful decannulation have yet to be identified. OBJECTIVE: This study aimed to explore the predictors of tracheostomy decannulation outcomes in individuals in PVS and to develop a nomogram. METHOD: In 2022, 872 people with tracheostomy in PVS were retrospectively enrolled and their data was randomly divided into a training set and a validation set in a 7:3 ratio. Univariate and multivariate regression analyses were performed on the training set to explore the influencing factors for decannulation and nomogram development. Internal validation was performed using 5-fold cross-validation. External validation was performed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) on both the training and validation sets. RESULT: Data from 610 to 262 individuals were used for the training and validation sets, respectively. The multivariate regression analysis found that duration of tracheostomy tube placement≥30 days (Odds Ratio [OR] 0.216, 95 % CI 0.151-0.310), pulmonary infection (OR 0.528, 95 %CI 0.366-0.761), hypoproteinemia (OR 0.669, 95 % CI 0.463-0.967), no passive standing training (OR 0.372, 95 % CI 0.253-0.547), abnormal swallowing reflex (OR 0.276, 95 % CI 0.116-0.656), mechanical ventilation (OR 0.658, 95 % CI 0.461-0.940), intensive care unit (ICU) duration>4 weeks (OR 0.517, 95 % CI 0.332-0.805), duration of endotracheal tube (OR 0.855, 95 % CI 0.803-0.907), older age (OR 0.981, 95 % CI 0.966-0.996) were risk factors for decannulation failure. Conversely, peroral feeding (OR 1.684, 95 % CI 1.178-2.406), passive standing training≥60 min (OR 1.687, 95 % CI 1.072-2.656), private caregiver (OR 1.944, 95 % CI 1.350-2.799) and ICU duration<2 weeks (OR 1.758, 95 % CI 1.173-2.634) were protective factors conducive to successful decannulation. The 5-fold cross-validation revealed a mean area under the curve of 0.744. The ROC curve C-indexes for the training and validation sets were 0.784 and 0.768, respectively, and the model exhibited good stability and accuracy. The DCA revealed a net benefit when the risk threshold was between 0 and 0.4. CONCLUSION: The nomogram can help adjust the treatment and reduce decannulation failure. REGISTRATION: Clinical registration is not mandatory for retrospective studies.

Conscientious Objection to Aggressive Interventions for Patients in a Vegetative State.

Some physicians refuse to perform life-sustaining interventions, such as tracheostomy, on patients who are very likely to remain permanently unconscious. To explain their refusal, these clinicians often invoke the language of "futility", but this can be inaccurate and can mask problematic forms of clinical power. This paper explores whether such refusals should instead be framed as conscientious objections. We contend that the refusal to provide interventions for patients very likely to remain permanently unconscious meets widely recognized ethical standards for the exercise of conscience. We conclude that conscientious objection to tracheostomy and other life-sustaining interventions on such patients can be ethical because it does not necessarily constitute a form of invidious discrimination. Furthermore, when a physician frames their refusal as conscientious objection, it makes transparent the value-laden nature of their objection and can better facilitate patient access to the requested treatment.

A practical model-based segmentation approach for improved activation detection in single-subject functional magnetic resonance imaging studies.

Functional magnetic resonance imaging (fMRI) maps cerebral activation in response to stimuli but this activation is often difficult to detect, especially in low-signal contexts and single-subject studies. Accurate activation detection can be guided by the fact that very few voxels are, in reality, truly activated and that these voxels are spatially localized, but it is challenging to incorporate both these facts. We address these twin challenges to single-subject and low-signal fMRI by developing a computationally feasible and methodologically sound model-based approach, implemented in the R package MixfMRI, that bounds the a priori expected proportion of activated voxels while also incorporating spatial context. An added benefit of our methodology is the ability to distinguish voxels and regions having different intensities of activation. Our suggested approach is evaluated in realistic two- and three-dimensional simulation experiments as well as on multiple real-world datasets. Finally, the value of our suggested approach in low-signal and single-subject fMRI studies is illustrated on a sports imagination experiment that is often used to detect awareness and improve treatment in patients in persistent vegetative state (PVS). Our ability to reliably distinguish activation in this experiment potentially opens the door to the adoption of fMRI as a clinical tool for the improved treatment and therapy of PVS survivors and other patients.

Long-term clinical evolution of patients with prolonged disorders of consciousness due to severe anoxic brain injury: A meta-analytic study.

BACKGROUND AND PURPOSE: The prognosis of prolonged (28 days to 3 months post-onset) disorders of consciousness (pDoC) due to anoxic brain injury is uncertain. The present study aimed to evaluate the long-term outcome of post-anoxic pDoC and identify the possible predictive value of demographic and clinical information. METHOD: This is a systematic review and meta-analysis. The rates of mortality, any improvement in clinical diagnosis, and recovery of full consciousness at least 6 months after severe anoxic brain injury were evaluated. A cross-sectional approach searched for differences in baseline demographic and clinical characteristics between survivors and non-survivors, patients improved versus not improved, and patients who recovered full consciousness versus not recovered. RESULTS: Twenty-seven studies were identified. The pooled rates of mortality, any clinical improvement and recovery of full consciousness were 26%, 26% and 17%, respectively. Younger age, baseline diagnosis of minimally conscious state versus vegetative state/unresponsive wakefulness syndrome, higher Coma Recovery Scale Revised total score, and earlier admission to intensive rehabilitation units were associated with a significantly higher likelihood of survival and clinical improvement. These same variables, except time of admission to rehabilitation, were also associated with recovery of full consciousness. CONCLUSIONS: Patients with anoxic pDoC might improve over time up to full recovery of consciousness and some clinical characteristics can help predict clinical improvement. These new insights could support clinicians and caregivers in the decision-making on patient management.

Effects of high-frequency repetitive transcranial magnetic stimulation on the nutritional status of patients in a persistent vegetative state: A pilot study.

Purpose: This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated. Methods: Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects' stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects' serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up. Results: (1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05). Conclusion: The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota-gut-brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.

Unlocking Hidden Awareness: Repurposing fMRI to Detect Levels of Consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging task because for someone to be deemed conscious, both wakefulness and awareness are required. Awareness has traditionally been assessed by examining physical responsiveness but in 2010, Monti et al. explored how using fMRI to measure brain activity in humans could help reclassify the state of consciousness in these patients. The findings, published in The New England Journal of Medicine, show that some brain regions are active when patients respond to an imagery or communication task. This is a seminal study because it demonstrates that patients who behaviourally appear to be in a vegetative or minimally conscious state may still have residual brain functions that would not be apparent from a clinical examination alone. Notably, it exemplified how fMRI can be repurposed as a communication tool for this subset of aware, but 'locked in', patients who appear unresponsive. From an educator's perspective, this paper is valuable because it is relevant to a broad audience, both introductory and advanced level undergraduate students. It introduces key concepts in cognitive and clinical neuroscience and encourages students to consider the connections between social issues and technology development in neuroscience. Finally, educators may use this paper to discuss and debate the nature of consciousness and the ethical implications that the use of fMRI for determining consciousness may have on medical ethics.

Case report: Tongdu Xingshen acupuncture for a patient with persistent vegetative state after herpes simplex virus encephalitis.

Introduction: A persistent vegetative state (PVS) can be caused by traumatic or non-traumatic brain injury. PVS is a complex clinical condition with numerous complications. Nursing care, medical treatment, and comprehensive rehabilitation are necessary to improve the outcomes of PVS. However, the prognosis remains unsatisfactory. Acupuncture therapy has been used as a rehabilitation strategy to treat patients with PVS in China, showing better results in the recovery of consciousness, intellectual capability, and motor function. Case description: We present the case of a 4-month-long PVS after herpes simplex virus encephalitis (HSVE) in a 3.5-year-old boy who underwent Tongdu Xingshen acupuncture integrated with Western medicine and rehabilitation. The patient regained consciousness post-treatment. His intelligence and motor function gradually recovered after seven treatment sessions. Conclusion: Tongdu Xingshen acupuncture is a potential complementary therapy to optimize clinical outcomes in PVS.

Behavioral effects in disorders of consciousness following transcranial direct current stimulation: A systematic review and individual patient data meta-analysis of randomized clinical trials.

Background: In patients with Disorders of Consciousness (DoC), recent evidence suggests that transcranial direct current stimulation (tDCS) can be a promising intervention for them. However, there has been little agreement on the treatment effect and the optimal treatment strategy for the tDCS in patients with DoC. Objective: In this meta-analysis of individual patient data (IPD), we assess whether tDCS could improve DoC patients' behavioral performance. We also determine whether these treatment effects could be modified by patient characteristics or tDCS protocol. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials until 7 April 2022 using the terms "persistent vegetative state," "minimally conscious state," "disorder of consciousness," or "unresponsive wakefulness syndrome," and "transcranial direct current stimulation" to identify Randomized Controlled Trials (RCTs) in English-language publications. Studies were eligible for inclusion if they reported pre- and post-tDCS Coma Recovery Scale-Revised (CRS-R) scores. From the included studies, patients who had incomplete data were excluded. We performed a meta-analysis to assess the treatment effect of the tDCS compared with sham control. Additionally, various subgroup analyses were performed to determine whether specific patient characteristics could modify the treatment effect and to find out the optimal tDCS protocol. Results: We identified 145 papers, but eventually eight trials (including 181 patients) were included in the analysis, and one individual data were excluded because of incomplete data. Our meta-analysis demonstrated a mean difference change in the CRS-R score of 0.89 (95% CI, 0.17-1.61) between tDCS and sham-control, favoring tDCS. The subgroup analysis showed that patients who were male or with a minimally conscious state (MCS) diagnosis were associated with a greater improvement in CRS-R score. We also found that patients who underwent five or more sessions of tDCS protocol had a better treatment effect than just one session. Conclusion: The result shows that tDCS can improve the behavioral performance of DoC patients. The heterogeneity of the treatment effect existed within the patients' baseline conditions and the stimulation protocol. More explorative studies on the optimal tDCS protocol and the most beneficial patient group based on the mechanism of tDCS are required in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022331241.

The Critical Role of Spreading Depolarizations in Early Brain Injury: Consensus and Contention.

BACKGROUND: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. METHODS: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. RESULTS: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. CONCLUSIONS: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.

Hydrogen inhalation promotes recovery of a patient in persistent vegetative state from intracerebral hemorrhage: A case report and literature review.

BACKGROUND: Persistent vegetative state (PVS) is a devastating and long-lasting clinical condition with high morbidity and mortality; currently, there are no available effective interventions. CASE SUMMARY: We report the case of an 11-year-old boy with PVS caused by severe intracerebral bleeding in the left hemisphere following anticoagulation treatment. The patient's PVS severity showed no notable improvement after 2-mo neuroprotective treatment and rehabilitation, including nerve growth factor and baclofen, hyperbaric oxygen, and comprehensive bedside rehabilitation therapies. Daily inhalation treatment (4-6 h) of high-concentration hydrogen (H2) gas (66.6% H2 + 33.3% O2) was provided. Surprisingly, the patient's orientation, consciousness, ability to speak, facial expressions, and locomotor function were significantly restored, along with improvements in essential general health status, after H2 gas inhalation treatment, which was consistent with stabilized neuropathology in the left hemisphere and increased Hounsfield unit values of computed tomography in the right hemisphere. The patient finally recovered to a near normal conscious state with a Coma Recovery Scale-Revised Score of 22 from his previous score of 3. CONCLUSION: Phase 1 clinical trials are needed to explore the safety and efficacy of H2 gas inhalation in patients with PVS.

Questioning Glutamate Excitotoxicity in Acute Brain Damage: The Importance of Spreading Depolarization.

BACKGROUND: Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s METHODS: Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. RESULTS: Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. CONCLUSIONS: Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate.

Tracheostomy Decannulation and Disorders of Consciousness Evolution.

BACKGROUND: Tracheostomy is a frequent surgical procedure in subjects with chronic disorders of consciousness (DOC). There is no consensus about safety of tracheostomy decannulation in this population.The aim of our study was to estimate if DOC improvement is a predictor for tracheostomy decannulation. Secondary outcomes include mortality rate and discharge destination. METHODS: We conducted an observational, retrospective, case-control study at a weaning and rehabilitation center (WRC). We included tracheostomized subjects with DOC admitted between August 2015 and December 2017. We matched groups based on the consciousness level at admission assessed withthe coma recovery scale revised (CRS-R). Subjects who were later decannulated formed the cases, while those that remained tracheostomized at the end of follow-up formed the controls. Improvement of DOC was defined as a progress in the categories of the CRS-R. RESULTS: 22 subjects were included in each group. No significant differences were found in clinical and demographic variables, except that controls had longer neurologic injury evolution (65.5 vs 51 days, P = .047), more tracheostomy days at admission to ourinstitution (53 vs 33.5, P = .02), and higher prevalence of neurological comorbidities (12 vs 4, P = .03). Subjects who improved their DOC had more chances of being decannulated (OR 11.28, 95% CI 1.96-123.08). Tracheostomy decannulation could not be achieved in most subjects who did not improve from vegetative state (VS) (OR 0.13, 95% CI 0.02-0.60). 8 subjects, however, could be decannulated in VS, with only one decannulation failure and no deaths. Mortality was higher in controls (0 vs 6, P = .02), especially among VS (0 vs 5, P = .049). No significant differences were found in discharge destination between groups. CONCLUSIONS: Subjects who improve their DOC are more likely to achieve tracheostomy decannulation. Some subjects in VS were decannulated, with lower mortality than those who remained tracheostomized.

¿Es proporcionado suspender la nutrición e hidratación artificial en pacientes con pronóstico incierto? Perspectiva nutricional y bioética

para llevar a cabo esta investigación, se revisó la literatura sobre el caso de Terri Schiavo, paciente que se encontraba en estado vegetativo persistente y quien falleció luego de dos semanas, después de que se le suspendiera su alimentación e hidratación; se validó su diagnóstico y se indagó si fue una paciente terminal, así como también se verificó la evidencia disponible, en relación con la hidratación y nutrición artificial en este tipo de pacientes, para determinar la concordancia de estas medidas. Esta información fue analizada desde la perspectiva nutricional y bioética; en la búsqueda bibliográfica se consultaron las bases de datos Scopus, Scielo y PubMed, con los criterios de búsqueda nutrición e hidratación artificial en pacientes terminales y de pronóstico incierto. Estos hallazgos fueron analizados con el modelo de proporcionalidad terapéutica de Calipari. Por lo anterior, se determinó que la nutrición e hidratación artificial configuraban tratamientos de carácter obligatorio u optativo para Terri. Sin embargo, pese a que no existe información concluyente sobre la nutrición e hidratación artificial en pacientes terminales, ni de pronóstico incierto, se recomienda la evaluación caso a caso de parte del equipo médico, para determinar la proporcionalidad de estos procedimientos en conjunto con el paciente y su familia. Cabe resaltar que son necesarios más estudios para proporcionar mejor evidencia que permita contar con elementos objetivos para una mejor toma de decisiones.

to carry out this research, the literature was reviewed on the case of Terri Schiavo, a patient who was in a persistent vegetative state and who died after two weeks, after her nutrition and hydration were suspended; her diagnosis was validated, and it was investigated whether she was a terminal patient, as well as the available evidence, was verified, in relation to artificial hydration and nutrition in this type of patients to determine the concordance of these measures. This information was analyzed from the nutritional and bioethical perspective; in the bibliographic search, the Scopus, Scielo, and PubMed databases were consulted with the search criteria nutrition and artificial hydration in terminal patients and patients with uncertain prognosis; these findings were analyzed with Calipari's therapeutic proportionality model. Therefore, it was determined that artificial nutrition and hydration are mandatory or optional treatments for Terri. However, there is no conclusive information on artificial nutrition and hydration in terminally ill patients, nor is the prognosis uncertain, and a case-by-case evaluation by the medical team is recommended to determine the proportionality of artificial nutrition and hydration, together with the patient and family. It should be emphasized that more studies are needed to provide better evidence to provide objective elements for better decision-making.

Para realizar esta pesquisa, foi revisada a literatura sobre o caso de Terri Schiavo, paciente que se encontrava em estado vegetativo persistente e que faleceu após duas semanas depois de sua alimentação e hidratação terem sido suspensas. Foi avaliado seu diagnóstico e questionado se foi uma paciente terminal, bem como verificada a evidência disponível quanto à hidratação e à nutrição artificiais nesse tipo de pacientes para determinar a concordância dessas medidas. Essa informação foi analisada sob a perspectiva nutricional e bioética; na busca bibliográfica, foram consultadas as bases de dados Scopus, SciELO e PubMed, com os critérios de busca "nutrição e hidratação artificiais em pacientes terminais e de prognóstico incerto". Esses achados foram analisados com o modelo de proporcionalidade terapêutica de Calipari. Assim, foi determinado que a nutrição e a hidratação artificiais configuram tratamentos de caráter obrigatório ou opcional para Terri. Contudo, não existe informação conclusiva sobre a nutrição e a hidratação artificiais em pacientes terminais, nem em pacientes com prognóstico incerto. É recomendada a avaliação por parte da equipe médica caso a caso para determinar a adequação da nutrição e da hidratação artificiais em conjunto com o paciente e sua família. Cabe ressaltar que mais estudos são necessários para proporcionar melhor evidência que permita contar com elementos objetivos para uma melhor tomada de decisões.

Development and reliability and validity testing of the assessment scale for patients with persistent vegetative state or minimally conscious state discharge from the anesthesia recovery room / 中国实用护理杂志

Objective:To develop and test the reliability and validity of the assessment scale for patients with persistent vegetative state (PVS) or minimally conscious state (MCS) discharge from the anesthesia recovery room after operation.Methods:From September 2018 to October 2020, three dimensions and 17 item pools were determined through literature review and discussion among the project members. Two rounds of expert consultation were conducted to determine the respiratory (R), circulatory (C), oxygenation (O), bispectral index (B) and neuromuscular monitoring (N) scale (RCOBN scale), the reliability and validity were tested. 87 patients with PVS or MCS after operation Affiliated Sichuan Bayi Rehabilitation Center of Chengdu University of Traditional Chinese Medicine were selected to verify the effectiveness.Results:In the first round, 23 questionnaires were distributed. The total score of experts was 50 ± 3, F=9.24, CV were 0.00-0.43. The Cronbach α coefficient of each dimension was 0.782-0.846, and the Cronbach α coefficient of the total scale was 0.813. In the second round, 10 questionnaires were distributed. The item-level content validity index was 0.7-1.0, the probability of random consistency ( Pc) was 0.001-0.117, the adjusted kappa value ( k*) was 0.567-1.000, and the sum of the index scores corresponding to k* > 0.74 was 8. The scale-level content validity index of the overall consistency was 0.87. The ratio of patients transferred out of PACU by two rounds of evaluation method was 100 : 96.55, and the difference was not statistically significant ( χ2=3.05, P>0.05). The time of the first round of assessment was significantly longer than that of the second round, which were (197 ± 52) s and (58 ± 14) s respectively. The difference was statistically significant ( t=26.52, P < 0.01). Conclusions:The RCOBN scale has high reliability and validity. It can be used as an assessment scale for patients with PVS or MCS to transfer out of PACU after surgery, and those with a total score of 8 can be transferred out of PACU.

Effects of acupuncture on nutritional status in patients in a persistent vegetative state: a prospective randomized controlled study / 针灸推拿医学（英文版）

Objective: To explore the effects of acupuncture on nutritional status in patients in a persistent vegetative state. Methods: A prospective randomized controlled trial was designed. A total of 66 patients in a persistent vegetative state were randomized into a control group and an observation group, with 33 cases in each group. The control group was given conventional treatment plus enteral nutrition support. The observation group was treated with additional Tiao Shen Jian Pi acupuncture therapy (acupuncture for spirit-regulating and spleen-invigorating) based on the same interventions in the control group. Both groups were treated for 8 weeks. The levels of total protein (TP), prealbumin (PA), albumin (Alb), and hemoglobin (Hb) were measured before and after treatment. The upper arm circumference and skinfold thickness of triceps brachii were measured. And the intestinal flora and fecal short-chain fatty acids contents were determined.Results: After treatment, the levels of TP, PA, Alb, and Hb in the control group were decreased (P<0.05), while in the observation group, compared with those before treatment, the levels of TP, PA, Alb, and Hb had no statistical differences (P>0.05), and the levels were all higher than those in the control group (P<0.05). The upper arm circumference and skinfold thickness of triceps brachii in both groups decreased (P<0.05), and the values of these two items in the observation group were higher than those in the control group (P<0.05). In the control group, the contents of Bifidobacterium and Lactobacillus in feces decreased (P<0.05), and the content of Enterococcus increased (P<0.05). In the observation group, the contents of Bifidobacterium and Lactobacillus in feces increased (P<0.05), and the content of Enterococcus decreased (P<0.05). The differences between the two groups were statistically significant (P<0.05). In the control group, the total content of fecal short-chain fatty acids and the contents of acetic acid and butyric acid in feces decreased (P<0.05). In the observation group, the total content of fecal short-chain fatty acids and the contents of acetic acid and butyric acid in feces increased (P<0.05) and were all higher than those in the control group (P<0.05). Conclusion: Acupuncture can improve nutrition-related blood indicators in patients in a persistent vegetative state and delay the decrease of upper arm circumference and skinfold thickness of triceps brachii, which may be related to the regulation of intestinal flora and fecal short-chain fatty acids contents.

Letter to the editor: COVID in patients with brain injury with a disorder of consciousness: a pathogenetic theory.

We recently published in this journal (Caronni and colleagues, Brain Injury, 2021-04-16) the first description of the spread of the SARS-CoV-2 infection in a cohort of brain injured patients with a disorder of consciousness (DOC). Surprisingly enough we showed that, in these patients, the COVID was moderate and did not result in fatalities. The pathogenesis of the COVID is characterized by the profound dysregulation of the immune system. To explain our findings, we speculated that the immunosuppression due to the brain injury could be protective against the development of the COVID in patients with DOC. More recently, a second group of authors (Marino and colleagues, PLoSOne, 2021-06-30) described the course of the COVID in an independent cohort of patients with DOC. Since our results were quite unexpected, we have been very comforted by the data reported by Marino and colleagues. Moreover, these data also offer a unique opportunity to further evaluate our theory regarding the COVID pathogenesis in patients with DOC. In the current Letter to the Editor it is shown that the independent data presented by Marino and colleagues do support our theory. Waiting for larger cohorts to further test it (and in case falsify it), our interpretation seems to remain valid.

Cranioplasty for patients with disorders of consciousness.

BACKGROUND: Cranioplasty (CP) is necessary for patients with disorders of consciousness (DOC) and skull defects. However, due to the complexity of these conditions, the surgical indications are conservative, and there are few published reports. This study aimed to assess the outcomes and complications of CP in patients with DOC, and to optimize the management of transcalvarial herniation (TCH) and hydrocephalus. METHODS: A total of 87 patients with DOC who underwent CP at our center between December 2016 and April 2019 were selected. The patients were divided into traumatic brain injury (TBI) and non-TBI groups, and the complications, outcomes, and costs were compared. Factors associated with prognosis and surgical complications were identified using multivariate logistic regression analysis. RESULTS: Postoperative complications occurred in 18 patients (20.7%). The complication rate was higher in the TBI group than in the non-TBI group (P=0.031). Preoperative ventriculoperitoneal shunt (VPS) was identified as a risk factor for incision complication (P=0.032), and non-traumatic cause tended to be a protective factor against postoperative hydrocephalus (P=0.055). One year after CP, 25 patients (28.7%) regained full consciousness [Extended Glasgow Outcome Scale (GOSE) ≥3] and 10 patients (11.5%) achieved partial self-care (GOSE =4). Multivariate analyses revealed that minimally conscious state (MCS) vs. vegetative state/unresponsive wakefulness syndrome (VS/UWS) (P=0.000) and early CP (P=0.023) were potential indicators for the recovery of consciousness. CONCLUSIONS: Our findings suggest that CP is safe in patients with DOC and may be beneficial for the recovery of consciousness. Early surgery and surgery for MCS provide better results. Timely CP in patients with TCH can help to reduce preoperative VPS, control incision complications, and detect and intervene in potential hydrocephalus.

Patient Outcomes in Disorders of Consciousness Following Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Individual Patient Data.

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC), such as minimally conscious and persistent vegetative state (MCS and PVS). Objective: In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) as a treatment in DoC to determine patient and protocol-specific factors associated with improved outcomes. Methods: We conducted a systematic review of PubMed, Ovid Medline, and Clinicaltrials.gov through April 2020 using the following terms: "minimally conscious state," or "persistent vegetative state," or "unresponsive wakefulness syndrome," or "disorders of consciousness" and "transcranial magnetic stimulation." Studies utilizing TMS as an intervention and reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores and subscores were included. Studies utilizing diagnostic TMS were excluded. We performed a meta-analysis at two time points to generate a pooled estimate for absolute change in CRS-R Index, and performed a second meta-analysis to determine the treatment effect of TMS using data from sham-controlled crossover studies. A linear regression model was also created using significant predictors of absolute CRS-R index change. Results: The search yielded 118 papers, of which 10 papers with 90 patients were included. Patients demonstrated a mean pooled absolute change in CRS-R Index of 2.74 (95% CI, 0.62-4.85) after one session of TMS and 5.88 (95% CI, 3.68-8.07) at last post-TMS CRS-R assessment. The standardized mean difference between real rTMS and sham was 2.82 (95% CI, -1.50 to 7.14), favoring rTMS. The linear regression model showed that patients had significantly greater CRS-R index changes if they were in MCS, had an etiology of stroke or intracranial hemorrhage, received 10 or more sessions of TMS, or if TMS was initiated within 3 months from injury. Conclusions: TMS may improve outcomes in MCS and PVS. Further evaluation with randomized, clinical trials is necessary to determine its efficacy in this patient population.

Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.