Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.

In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47-0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.

Functional MRI evaluation of hyperbaric oxygen therapy effect on hand motor recovery in a chronic post-stroke patient: a case report and physiological discussion.

Introduction: Impairments in activities of daily living (ADL) are a major concern in post-stroke rehabilitation. Upper-limb motor impairments, specifically, have been correlated with low quality of life. In the current case report, we used both task-based and resting state functional MRI (fMRI) tools to investigate the neural response mechanisms and functional reorganization underlying hyperbaric oxygen therapy (HBOT)-induced motor rehabilitation in a chronic post-stroke patient suffering from severe upper-limb motor impairment. Methods: We studied motor task fMRI activation and resting-state functional connectivity (rsFC) in a 61-year-old right-handed male patient who suffered hemiparesis and physical weakness in the right upper limb, 2 years after his acute insult, pre- and post-treatment of 60 daily HBOT sessions. Motor functions were assessed at baseline and at the end of the treatment using the Fugl-Meyer assessment (FMA) and the handgrip maximum voluntary contraction (MVC). Results: Following HBOT, the FMA score improved from 17 (severe impairment) to 31 (moderate impairment). Following the intervention during trials involving the affected hand, there was an observed increase in fMRI activation in both the supplementary motor cortex (SMA) and the premotor cortex (PMA) bilaterally. The lateralization index (LI) decreased from 1 to 0.63, demonstrating the recruitment of the contralesional hemisphere. The region of interest, ROI-to-ROI, analysis revealed increased post-intervention inter-hemispheric connectivity (P = 0.002) and a between-network connectivity increase (z-score: 0.35 ± 0.21 to 0.41 ± 0.21, P < 0.0001). Seed-to-voxel-based rsFC analysis using the right SMA as seed showed increased connectivity to the left posterior parietal cortex, the left primary somatosensory cortex, and the premotor cortex. Conclusion: This study provides additional insights into HBOT-induced brain plasticity and functional improvement in chronic post-stroke patients.

Impact of high-resolution intracranial vessel wall magnetic resonance imaging on diagnosis in patients with embolic stroke of unknown source.

BACKGROUND: The mechanism responsible for stroke in patients with embolic stroke of unknown source (ESUS) often remains unknown despite extensive investigations. We aimed to test whether high-resolution intracranial vessel wall MR imaging (icVWI) can add to the diagnostic yield in these patients. PATIENTS AND METHODS: Patients with ESUS were prospectively included into an ongoing registry. Patients that underwent icVWI as part of their diagnostic workup were compared to those that did not have an icVWI. Patients with icVWI positive for intracranial vulnerable plaques were than compared to those without evidence of plaque vulnerability on VWI. RESULTS: A total of 179 patients with ESUS were included and 48 of them (27%) underwent icVWI. Patients that had an icVWI scan were significantly younger, had lower rates of ischemic heart disease and prior disability as well as significantly lower stroke severity. On regression analysis the only factor that remained associated with not obtaining an icVWI scan was increasing age (Odds ratio [OR] 0.97/year, 95% confidence intervals [CI] 0.95-0.97). Among patients that had an icVWI scan 28 (58%) had evidence of plaque enhancement on VWI in the same distribution of the stroke and the remaining 20 studies were negative. The relative proportion of stroke presumed to be secondary to intracranial non-stenotic atheromatous disease increased from 15% in patients without icVWI scans to 58% among patients with icVWI scans (p = 0.001). On regression analysis the only factor that was associated with vulnerable plaques on icVWI was smoking (OR 11.05 95% CI 1.88-65.17). CONCLUSIONS: icVWI can add significant information relevant to stroke pathogenesis and treatment in patients with ESUS and a negative initial exhaustive diagnostic workup.

Diagnostic Yield of High-Resolution Vessel Wall Magnetic Resonance Imaging in the Evaluation of Young Stroke Patients.

(1) Background: The mechanism responsible for stroke in patients younger than 50 often remains unknown. This study was designed to assess whether high-resolution intracranial vessel wall MR imaging (icVWI) may be instrumental in determining stroke cause. (2) Methods: Young stroke patients with and without an identified cause of stroke despite an exhaustive investigation were prospectively included. Patients who underwent icVWI were compared to those who did not. We next compared patients with and without intracranial vulnerable plaques on icVWI. (3) Results: Overall, 47 young stroke patients were identified over the span of 2 years and included in this study. Of those, 20 (42%) underwent intracranial icVWI. Cancer prevalence was higher among patients who did not have an icVWI study (19% vs. 0% p = 0.042) but there were no other significant differences between patients who had an icVWI study and those who did not have an icVWI. Among patients who had an icVWI, 11 (55%) had vulnerable plaques and the remaining nine studies were negative. Patients with positive icVWI scans had significantly higher stroke severity at admission (mean ± SD NIHSS score 5.5 ± 3.5 vs. 1.7 ± 2.3, p = 0.012). Patients with positive icVWI scans were more often treated with antiplatelets upon discharge (100% vs. 67%, p = 0.038). (4) Conclusions: icVWI can add significant information relevant to stroke pathogenesis and secondary prevention among young stroke patients with a negative exhaustive diagnostic workup.

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial.

INTRODUCTION: Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. METHODS: In this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n = 37) or sham treatment (n = 36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. RESULTS: The ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p < 0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F = 7.81, P = 0.007). The efficacy measure had significant group-by-time interactions (F = 5.98, p = 0.017) in the amygdala circuit. CONCLUSIONS: This study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Variable phenotype of Knobloch syndrome due to biallelic COL18A1 mutations in children.

PURPOSE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele. Our aim is to report the clinical and genetic findings of four Israeli children affected by Knobloch syndrome. METHODS: Retrospective study of four patients diagnosed with Knobloch syndrome, who underwent full ophthalmic examination, electroretinography, and neuroradiologic imaging. Genetic analysis included whole exome sequencing (WES) and Sanger sequencing. RESULTS: The four patients included in this study had high myopia and nystagmus at presentation. Ocular findings included vitreous syneresis, macular atrophy, macular coloboma, and retinal detachment. One child had iris transillumination defects and an albinotic fundus, initially leading to an erroneous clinical diagnosis of albinism. Electroretinography revealed a marked cone-rod pattern of dysfunction in all four children. Brain imaging demonstrated none to severe occipital pathology. Cutaneous scalp changes were present in three patients. WES analysis, confirmed by Sanger sequencing revealed COL18A1 biallelic null mutations in all affected individuals, consistent with autosomal recessive inheritance. CONCLUSIONS: This report describes variable features in patients with Knobloch syndrome, including marked lack of eye pigment similar to albinism in one child, macular coloboma in two children as well as advanced cone-rod dysfunction in all children. One patient had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of this syndrome, with its variable phenotype may aid early diagnosis, monitoring for potential complications, and providing appropriate genetic counseling.

Unconscious defensive medicine: The case of erythrocyte sedimentation rate.

BACKGROUND: We investigated physician rationale for and against performing routine erythrocyte sedimentation rate (ESR) tests during hospital admissions. METHODS: A comparative, descriptive, prospective study among 82 physicians in 15 departments of internal medicine from two University Medical Centers - A and B - in Israel was conducted between July and August 2004. Reasons for physicians' use of ESR were examined using a confidential questionnaire. A panel of four experts reviewed the need to perform an ESR test in 100 patients' files from center B. The main outcome measures were the use of ESR in routine hospital admissions and reasons for use. RESULTS: Forty-four vs. zero physicians from medical centers B and A, respectively, routinely perform ESR tests for all admitted patients (p<0.001). According to the experts, in only 10-30% of the 67 new patients could ESR tests have been of some value. Reasons for performing ESR routinely were as follows: to identify severe and "hidden" diseases (21/44, 47.7%); because it is crucial for all patients, both new and returning (10/44, 22.7%); because it is a guideline from department head (6/44, 13.6%); it is recommended in the literature (5/44, 11.4%); don't know why (2/44, 4.5%); defensive medicine (1/44, 2.3%); and other (6/44, 13.6%). CONCLUSION: Routine use of ESR tests on admission can be explained by old habits and by an unconscious concern about liability, i.e., unconscious defensive medicine.

State-of-the-art pathology: new WHO classification, implications, and new developments.

To keep up with advances in central nervous system (CNS) tumor diagnosis and discovery of new entities, the classification of these tumors requires periodic review and revision. Since the initial 1979 publication from the World Health Organization (WHO) of Histological Typing of Tumours of the Central Nervous System, 3 further editions have been published, cataloging the advances in CNS tumor classification and diagnosis over the past 3 decades. In this article, we discuss select new additions to the current classification, including new diagnostic tools, differential diagnoses, and management implications.

The aortic root: comparison of measurements from ECG-gated CT angiography with transthoracic echocardiography.

PURPOSE: The purpose of this study was to compare the measurements of the aortic root obtained from electrocardiographically (ECG)-gated computed tomography (CT) angiography (CTA) to the measurements obtained from transthoracic echocardiography (TTE). MATERIALS AND METHODS: This was a retrospective study in a patient population scanned at our institution between December 2005 and January 2007 with retrospectively ECG-gated CTA. ECG-gated CTA was performed with a 64-section helical CT scanner (Light speed, VCT, GE, Milwaukee, WI). Sixty-eight patients; 51 men and 17 women were included in this study. Aortic root diameters were measured by using double oblique reconstruction from axial source images. The TTE measurements of the aortic root were obtained from the reports that were performed within 2 months of CTA. RESULTS: The average aortic root diameter measured by TTE was 33+/-4.1 mm; on CTA it was 36.9+/-3.8 mm. The median difference between the 2 measurements was 3.9 mm which was significant (P<0.0001). In patients whose aortic root measurements with CTA were normal, the TTE measurements were also normal. However, in the group of patients with dilated aortic roots by CTA, TTE measurements were significantly lower and many were normal. In the group of patients with dilated aortic root by TTE, the CTA measurements of the aortic root were similarly increased. CONCLUSIONS: Retrospective comparison of TTE and CTA measurements of the aortic root reveal that TTE measurements are substantially lower or even normal in patients found to have dilated aortic root by CTA.

Detection of recurrence in patients with rectal cancer: PET/CT after abdominoperineal or anterior resection.

PURPOSE: To assess diagnostic accuracy of combined positron emission tomography (PET) and computed tomography (CT) in detection of pelvic recurrence in patients with rectal cancer who underwent abdominoperineal or anterior resection. MATERIALS AND METHODS: Sixty-two patients were enrolled; 37 were men, and 25 were women. Seventeen patients underwent abdominoperineal resection and 45 underwent anterior resection with an anastomosis in the pelvic region before referral for PET/CT. Pelvic sites of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) uptake were rated separately on PET and PET/CT images as benign or malignant on the basis of shape, location, and intensity of (18)F FDG uptake (1-2 = benign and/or physiologic, 3 = equivocal, 4-5 = malignant). Two readers interpreted images in consensus. Altered pelvic anatomy and presence of presacral abnormalities were assessed with CT. Pelvic recurrence was confirmed with histologic analysis or clinical and imaging follow-up. Sensitivity, specificity, positive and negative predictive values, and accuracy of PET and PET/CT in the detection of pelvic recurrence were compared with lesion- and patient-based analyses by using the chi(2) test. Clinical relevance of PET/CT assessment was determined. RESULTS: Of 81 pelvic sites with increased (18)F FDG uptake, 44 were malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for differentiating malignant from benign (18)F FDG uptake in the pelvis were 98%, 96%, 90%, 97%, and 93% for PET/CT and 82%, 65%, 73%, 75%, and 74% for PET, respectively. The most common cause for false-positive interpretation of PET findings was physiologic (18)F FDG uptake in displaced pelvic organs. Presacral CT abnormalities were present in 30 (48%) of 62 patients, and seven (23%) abnormalities were malignant. PET/CT was used to distinguish benign and malignant presacral abnormalities with a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 96%, 88%, and 100%, respectively. PET/CT findings were clinically relevant in 29 (47%) of 62 patients. CONCLUSION: PET/CT is an accurate technique in the detection of pelvic recurrence after surgical removal of rectal cancer.