Traumatic Brain Injury Induced Hypopituitarism: The Need and Hope of Rehabilitation

Traumatic brain injury is a leading cause of death and disability in developed countries. Damage caused by focal and diffuse lesions produces symptoms involving most major medical systems as well as symptoms of neurological and psychological origin. The severity of a traumatic brain injury is difficult to assess, and therefore, an initial accurate prognosis is difficult as well. Present treatments focus on relieving symptoms without adequately addressing the underlying cause of those symptoms. Recent studies have shown anterior pituitary deficiencies to be common amongst survivors of TBI. As many symptoms ascribed to a TBI are similar to the symptoms of hypopituitarism, it is possible that treatment of these deficiencies will improve functioning and the quality of life for survivors of traumatic brain injuries.     

High Risk of Hypogonadism After Traumatic Brain Injury: Clinical Implications

Several recent studies have convincingly documented a close association between traumatic brain injury (TBI) and pituitary dysfunction. Post-traumatic hypogonadism is very common in the acute post-TBI phase, though most cases recover within six to twelve months following trauma. The functional significance of early hypogonadism, which may reflect adaptation to acute illness, is not known. Hypogonadism persists, however, in 10–17% of long-term survivors. Sex steroid deficiency has implications beyond psychosexual function and fertility for survivors of TBI. Muscle weakness may impair functional recovery from trauma and osteoporosis may be exacerbated by immobility secondary to trauma. Identification and appropriate and timely management of post-traumatic hypogonadism is important in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated sex steroid deficiency.     

Improving motor and cognitive recovery following severe traumatic brain injury using advanced emotional audio-video stimulation: Lessons from a case report

Rationale:It is estimated that about 6 million people suffer from severe traumatic brain injury (TBI) each year (73 cases per 100,000 people). TBI may affect emotional, sensory-motor, cognitive, and psychological functions with a consequent worsening of both patient and his/her caregiver''s quality of life. In recent years, technological innovations allowed the development of new, advanced sensory stimulation systems, such as Neurowave, to further stimulate residual cognitive abilities and, at the same time, evaluate residual cognition.Patient concern:An 69-year-old Italian man entered our neurorehabilitation unit with a diagnosis of minimally conscious state following severe TBI. He breathed spontaneously via tracheostomy and was fed via percutaneous gastrostomy. At the neurological examination, the patient showed severe tetraparesis as he showed fluctuating alertness and responsiveness to external stimuli and opened the eyes without stimulation.Diagnosis:Patient was affected by subarachnoid hemorrhage and frontotemporal bilateral hematoma, which were surgically treated with decompressive craniotomy and subsequent cranioplasty about 6 months before.Interventions:The patient underwent a neuropsychological and clinical evaluation before (T0) and after a conventional rehabilitation cycle (T1), and after a Neurowave emotional stimulation-supported rehabilitative cycle (T2).Outcomes:Following conventional rehabilitation (T1), the patient achieved a partial improvement in behavioral responsiveness; there was also a mild improvement in the caregiver''s distress. Conversely, Neurowave emotional stimulation session determined (at T2) a significant improvement of the patient''s behavioral responsiveness, cognition, and in the caregiver''s distress. The P300 recording in response to the NES showed a significant change of P300 magnitude and latency.Discussion:Our data suggest that emotional-integrated sensory stimulation using adequate visual stimuli represents a beneficial, complementary rehabilitative treatment for patients in minimally conscious state following a severe TBI. This may occur because stimuli with emotional salience can provide a reliable motivational resource to stimulate motor and cognitive recovery following severe TBI.     

The Consequences of Traumatic Brain Injury on Cerebral Blood Flow and Autoregulation: A Review

In this decade, the brain argueably stands as one of the most exciting and challenging organs to study. Exciting in as far as that it remains an area of research vastly unknown and challenging due to the very nature of its anatomical design: the skull provides a formidable barrier and direct observations of intraparenchymal function in vivo are impractical. Moreover, traumatic brain injury (TBI) brings with it added complexities and nuances. The development of irreversible damage following TBI involves a plethora of biochemical events, including impairment of the cerebral vasculature, which render the brain at risk to secondary insults such as ischemia and intracranial hypertension. The present review will focus on alterations in the cerebrovasculature following TBI, and more specifically on changes in cerebral blood flow (CBF), mediators of CBF including local chemical mediators such as K⁺, pH and adenosine, endothelial mediators such as nitric oxide and neurogenic mediators such as catecholamines, as well as pressure autoregulation. It is emphasized that further research into these mechanisms may help attenuate the prevalence of secondary insults and therefore improve outcome following TBI.     

Dexamethasone for the treatment of traumatic brain injured patients with brain contusions and pericontusional edema: Study protocol for a prospective,randomized and double blind trial

Background:Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated.Methods:The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4 mg/6 h (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6 months after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12 days of treatment; results of the neuropsychological tests one month and 6 months after TBI. The main analysis will be on an “intention-to-treat” basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1–6) and favorable outcome (GOSE 7–8). Efficacy will also be analyzed using the ''sliding dichotomy’. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alpha = 5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery.Discussion:This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients.Trial Registration:eudraCT: 2019–004038–41; Clinical Trials.gov: {"type":"clinical-trial","attrs":{"text":"NCT04303065","term_id":"NCT04303065"}}NCT04303065.     

Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study

BackgroundBrain metastases (BMs) develop in 20–65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.MethodsThis trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18–75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).ResultsFrom July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1–37.4 months]. The median OS was 26 months (95% CI: 17.0–54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.ConclusionsApatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.     

The impact of treatment on 3 years' outcome for heroin dependence: findings from the Australian Treatment Outcome Study (ATOS)

AIM: To examine the impact of treatment for heroin dependence on drug use, injection-related risk-taking, health problems, criminality and general physical and mental health over 3 years among heroin-dependent Australians. DESIGN: Longitudinal prospective cohort study. PARTICIPANTS: A total of 615 heroin users enrolled in the Australian Treatment Outcome Study; 94.5% of the sample completed at least one follow-up interview over 36-month follow-up. FINDINGS: The proportion who reported using heroin in the preceding month continued to decrease significantly from baseline to 24-month follow-up (99% versus 35%), with this rate remaining stable to 36-month follow-up. The reduction in heroin use was accompanied by reductions in other drug use. There were also substantial reductions in risk-taking, crime, injection-related health problems and improvements in general physical and mental health. Positive outcomes were associated with more time in maintenance therapies and residential rehabilitation and fewer treatment episodes. Time spent in detoxification was not associated with positive outcomes. Major depression was also associated consistently with poorer outcome. CONCLUSIONS: At 3 years, there were impressive reductions in drug use, criminality, psychopathology and injection-related health problems following treatment exposure.     

The development of hepatocellular carcinoma from liver cirrhosis during a follow-up study

A prospective study was carried out in 126 cases with liver cirrhosis attending the outpatient clinic of Hepatology of the Department of Internal Medicine, Dr. Cipto Mangunkusmo Hospital Jakarta, between August 1,1982 and Dec. 31, 1985. The patients consisted of 82 men and 44 women and there were 45 HBsAg positive cases (36.7%). HBeAg was posotive in 35.6% (16/45) and 40.0% were antiHBe positive while both markers were negative in 24.4%. During the follow-up study 27 cases died. The cause of death was due to variceal bleeding in 9 cases (33.3%) and hepatic failure in 9 cases (33.3%). In 6 cases (22.2%) hepatocellular carcinoma (HCC) was the cause of death. Nine cases out of 94 traceable cases (13.7%) were developed HCC. They consisted of 4 cases out of 29 cases (13.8%) with HBsAg positive and 5 cases out of 65 cases (7.7% ). But no significant difference was observed between both groups. The length of observation period from the first time of diagnosis until development of HCC was from 1 to 6 years with an average of 2.9 years. Financial support from Japan Society for Promotion Science is acknowledged.     

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

The effect of loneliness and change in loneliness on self-rated health (SRH): a longitudinal study among aging people

The association between adverse health and loneliness among aging people is known, but most of the studies are cross-sectional. In addition, the associations between changes in loneliness with health are less well known, especially in the case of aging people. The present study examined whether absence of loneliness in 2005 predicted subsequent good SRH in 2008, and whether changes in loneliness were associated with SRH in 2008. Longitudinal, questionnaire-based data were collected from three age cohorts (born in 1926-30, 1936-40, and 1946-50) living in southern Finland. Baseline data was collected in 2002 (n = 2815, 66%); the follow-ups were done in 2005 (n = 2476, 60%) and 2008 (n = 2064, 73%). Logistic regression analyses were used to derive the results. Never or seldom experiencing loneliness was a strong predictor for good SRH. In addition, good health was common among those who never felt lonely. Among men the group experiencing decreasing loneliness had the highest OR of good health. Thus, loneliness is a significant contributor to poor SRH among aging people. In addition, favorable SRH is indicated not only by the absence of loneliness at both measurement points, but also by decreased loneliness. Preventing loneliness is important for health promotion.     

The short-term outcomes of nonintubated anesthesia compared with intubated anesthesia in single-port video-assisted lung surgery in enhanced recovery after thoracic surgery: results from a single-center retrospective study

BackgroundNonintubated anesthesia avoids invasive tracheal intubation operations and reduces trauma. in addition, it has advantages in lung surgery in some patients with poor lung function, in line with the concept of rapid recovery. However, few studies have discussed the clinical significance of Enhanced recovery after surgery (ERAS) combined with nonintubated anesthesia in single-port video-assisted thoracoscopic surgery (VATS). We conducted a retrospective study to examine the safety and availability of nonintubated anesthesia single-port video-assisted lung surgery (NI-SP-VALS) combined with ERAS programs in patients.MethodsThis was a single-center retrospective study. All patients were preoperatively diagnosed with lung nodules and underwent NI-SP-VALS or intubated anesthesia SP-VALS (I-SP-VALS) combined with ERAS programs between July 2021 and March 2022. Short-term postoperative outcomes were compared in 2 cohorts.ResultsIn total, 272 patients were included. Among them, 91 patients received NI-SP-VALS combined with ERAS programs (observation group), and 181 underwent intubation anesthesia (control group). Baseline data were statistically different between the two groups, and 1:1 propensity score matching (PSM) matching was used. A total of 73 patients remained in each group after PSM, and baseline characteristics were not significantly different between the 2 cohorts. The time of hospital stay [4.00 (4.00–5.00) vs. 44.50 (0.00–5.75) d; P=0.029] and catheter stay [0.50 (0.20–2.00) vs. 2.00 (2.00–2.00) d; P<0.001] were significantly shorter, the white blood cell count (WBC) [9.45 (8.08–11.30) vs. 11 (8.50–12.80)/L; P=0.009] and the lowest SpO₂ in operation [96.00 (94.00–97.50) vs. 97.00 (95.00–98.50); P=0.035] were also lower in the nonintubated group than those of the intubated group. No differences were observed in variables of intraoperation, other routine blood indexes, postoperative drainage, postoperative medicine use, postoperative symptoms, complications, hospitalization expenses, postoperative follow-up index, or self-assessment of anxiety.ConclusionsThe data after PSM shows that compared with intubated anesthesia, NI-SP-VALS combined with ERAS programs is safe and effective. Nonintubated anesthesia promotes rapid recovery of patients and reduces postoperative inflammatory reactions. Hence, nonintubated anesthesia may conform to the idea of ERAS and has application value in thoracic surgery.     

Electrophysiologic Characteristics of Wide QRS Complexes during Pharmacologic Termination of Sustained Supraventricular Tachycardias with Verapamil and Adenosine: Observations from Electrophysiologic Study

Background: In this study we evaluate wide QRS complexes observed during pharmacologic termination of supraventricular tachycardias. Methods: Patients with supraventricular tachycardia, undergoing electrophysiologic study were enrolled. 12 mg of adenosine or 10 mg of verapamil were administered during tachycardia, under continuous monitoring of intaracardiac and surface electrocardiograms. Electrocardiographic features of ventricular ectopy were noted. Results: Seventy‐four patients were enrolled. 48 patients were randomized to adenosine and 26 to verapamil. Five different appearance patterns of ventricular ectopy were observed during termination of tachycardias. All wide QRS complexes were of ventricular origin and all of them were observed during the termination of tachycardia. Adenosine more frequently resulted in appearance of ventricular beats (15.4% vs 41.7%, P = 0.003), and this was more frequently observed in patients with atrioventricular nodal reentrant tachycardia. Patients with ventricular beats were younger than those without, in both, verapamil (47.5 ± 15.6 vs 65.0 ± 8.8 years, P = 0.04) and adenosine (40.9 ± 13.8 vs 49.7 ± 16.8, P = 0.03) groups. Left bundle branch block (LBBB)/superior axis morphology was most frequent morphology in adenosine group (55%). Two of 4 patients in verapamil group displayed LBBB/inferior axis QRS morphology and another 2 patients displayed LBBB/superior axis morphology. Conclusions: Noncatheter induced, five different appearance patterns and four distinct morphologies of ventricular origin were observed. Most of them do not directly terminate tachycardia, but are associated with its termination and are not observed in ongoing tachycardia.     

The Impact of Catheter Ablation on the Dynamic Function of the Left Atrium in Patients with Atrial Fibrillation: Insights from Four‐Dimensional Computed Tomographic Images

Functional Evaluation of the LA by Dynamic CT. Introduction: Elucidating the functional properties and remodeling process of the entire left atrium (LA) is important not only for offering the mechanistic insight into atrial fibrillation (AF) but also for assessing the effectiveness of catheter ablation. Methods: We included 65 patients with paroxysmal AF and 29 controls. Baseline multidetector computed tomography (MDCT) was acquired in all subjects and a follow‐up MDCT was available in 48 patients after pulmonary vein and LA ablation. The 3‐dimensional images at atrial end‐diastole (ED) and end‐systole (ES) were analyzed. Results: The LA volume (ED: 61.11 ± 15.94 vs 54.12 ± 8.94 mL/m², P = 0.03; ES: 45.29 ± 17.64 vs 33.38 ± 7.78 mL/m², P < 0.001) was increased, and ejection fraction (EF) (26.93 ± 13.40 vs 38.09 ± 11.62%, P < 0.001) decreased in AF patients as compared to controls. After ablation, the ES LA volume (44.73 ± 14.93 vs 38.04 ± 11.51 mL/m², P = 0.04) decreased and the LA EF (25.04 ± 13.13 vs 30.82 ± 7.85%, P = 0.03) increased in patients without any AF recurrence. The wall motion (WM) analysis of the 18 segments of LA revealed increased motional magnitudes of entire LA except for the anterior roof. In contrast, the volume, EF, and WM of LA remained similar in patients with recurrence. Conclusion: Dilated LA with global hypokinesia was noted in AF patients. Improved LA transport function was demonstrated in patients without any recurrence after ablation. However, the anatomic and functional reverse remodeling was not significant in patients with AF recurrence. (J Cardiovasc Electrophysiol, Vol. 21, pp. 270–277, March 2010)     

Novel RT-PCR Using Sugar Chain-Immobilized Gold-Nanoparticles Correlates Patients’ Symptoms: The Follow-Up Study of COVID-19 Hospitalized Patients

Background: The transmissible capacity and toxicity of SARS-CoV-2 variants are continually changing. We report here the follow-up study of hospitalized COVID-19 patients from 2020 to 2022. It is known that the PCR diagnosis for hospitalized patients sometimes causes confusion because of the incompatibility between their diagnosis and symptoms. We applied our sugar chain-immobilized gold-nanoparticles for the extraction and partial purification of RNA from specimens for quantitative RT-PCR assay and evaluated whether the results correlate with patients’ symptoms. Methods and Results: Saliva specimens were taken from hospitalized patients with mild or moderate symptoms every early morning. At the time of RT-PCR diagnosis, two methods for the extraction and partial purification of RNA from the specimen were performed: a commonly used Boom (Qiagen) method and our original sugar chain-immobilized gold nanoparticle (SGNP) method. For symptoms, body temperature and oxygen saturation (SpO₂) of patients were monitored every 4 h. Conclusions: It was clear that patients infected with the Delta variant needed more time to recover than those with the Omicron variant, and that the SGNP method showed more realistic correlation with the symptoms of patients compared with the common Qiagen method.