Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Usefulness of interim analyses in portending study results in antipsychotic and antidepressant trials.

It is unknown whether interim analyses portend final study results. Fatigue, pressure to complete trials and recruitment differences may mitigate against this. We examined the similarity of efficacy results of the first and second half of recruited patients to complete trials and explore possible intervening variables. Using data from the NewMeds repository of patient level data from placebo-controlled randomized trials of antipsychotics (AP) (22 studies, n=7056) and antidepressants (AD) (39 studies, n=12,217) we compared treatment effect size (placebo vs. active treatment) of the first and second half of patients recruited in completed trials. We found that in AP studies median difference in treatment effect between cohorts was -0.03, indicating that overall first and second cohorts yielded similar results. In AD studies, median difference between cohorts was 0.04, indicating that overall the second cohort had slightly larger active-placebo-difference. Overall, on average there were minimal differences in effect size between the first and the second cohorts, and in 30 of 39 trials interim results were a good estimate of the results on the 2nd cohort. In AD trials first and second cohort results were more similar when the proportion of patients per study centre and recruitment time of the two cohorts was similar. Results suggest that interim analyses in AD and AP studies may reliably serve to estimate ultimate effects and, at least in AD trials, are more accurate when the same sites are used to a similar extent and recruitment time of the two consequent cohorts is similar.

vRNA structured population model for Hepatitis C Virus dynamics.

Improvements in the understanding of the Hepatitis C Virus (HCV) life-cycle have led to the identification of targets and the development of drugs affecting the intracellular reproduction of the virus. These advancements have presented new modeling challenges as the classic models have focused on describing the macroscopic viral kinetics only. Our primary objective is to apply the existing theory of Physiologically Structured Population (PSP) modeling to describe dynamics of viral RNA (vRNA) in infected hepatocytes of patients receiving treatment with Direct-acting Antiviral Agents (DAA). Using vRNA as a physiological structure this work expands on previous structured population models allowing exploration of micro- and macroscopic implications of such treatments. The PSP model provides a description of vRNA distribution in the infected cells at steady state and its time evolution following treatment. The long term behavior of the model predicts viral load time courses in plasma and permits to quantify conditions for the virus eradication. Finally, we demonstrate that PSP models can account for additional structures, which are essential for the viral replication process with potentially far reaching implications in our understanding of HCV infections and treatment options.

A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia.

Acute studies suggested a therapeutic benefit for fundus-relaxing drugs in functional dyspepsia (FD) with visceral hypersensitivity (VH) to gastric distention or impaired accommodation (IA), but long-term studies are lacking. R-137696 is a serotonin-1A (5-HT(1A)) receptor agonist which relaxes the proximal stomach in man. Our aim was to investigate the influence of R-137696 on symptoms in FD with VH or IA. Randomized, double-blind, placebo-controlled, parallel group study of 4 weeks R-137696 2 mg t.i.d. in FD with VH or IA. Symptoms were assessed using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) total score and individual symptom subscales. Barostat studies were performed before and after 4 weeks of treatment. Fifty-three patients (33 VH and 20 IA), 18 men, mean age 40 +/- 13 years were recruited. Twenty-four received placebo and 29 received R-137696. In VH patients, both placebo and R-137696 improved total symptom scores, with a tendency for superiority of placebo (-1.12 vs-0.51, P = 0.07). Placebo was superior for the subscales of early satiety, bloating, fullness and discomfort (all P < 0.05). In IA, both placebo and R-137696 had no significant influence on total or individual symptom scores (-0.08 and -0.27). In VH, both placebo and R-137696 increased the discomfort volume, without a statistical difference between both arms (+120 and +164 mL). In IA, both placebo and R-137696 enhanced accommodation, without a statistical difference between both (+77 and +159 mL). Adverse events were similar for drug and placebo. A 4-week administration of the fundus-relaxing 5-HT(1A) agonist R-137696 failed to significantly improve symptoms, VH or gastric accommodation compared to placebo.

Demonstration of tissue alterations by ultrasonography, magnetic resonance imaging and spectroscopy, and histology in breast cancer patients without lymphedema after axillary node dissection.

Estimates of the incidence of arm swelling after axillary lymph node dissection for breast cancer range from 10 to 37%. Yet the subjective sensation of edema is described in at least 54% of patients. The purpose of this research was to examine the structural changes occurring in the subcutaneous tissue that might explain these subjective complaints using multiple imaging modalities. Two female cadavers with unilateral breast amputation and axillary dissection were studied. The dermal and subcutaneous layers of both arms were visualized with high frequency ultrasonography, and magnetic resonance imaging and spectroscopy (MRS), and tissue biopsies were taken for histological evaluation. On the operated side, ultrasound imaging showed a hyperechogenic subcutis and the fat-to-water relationship in adipose cells was higher as measured by MRS. Dissection of the arms revealed structural adipose tissue changes, which were confirmed by microscopic evaluation.

The influence of the novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers.

As fundic dysaccommodation represents one of the pathophysiological mechanisms underlying functional dyspepsia, gastric relaxant agents may serve as a new treatment of this disorder. Previous studies have suggested the involvement of 5HT1 receptors in the control of gastric tone. Our aim was to study the effect of R137696, a novel 5HT1A agonist, on fundus sensorimotor function in healthy volunteers. The effect of single oral doses (1-2 mg) R137696 was evaluated in a double-blind, placebo-controlled manner on fasting fundic volume, visceral perception, distension-evoked symptoms and fundic compliance in 21 healthy male subjects. R137696 increased the proximal stomach volumes in a dose-dependent manner. Distention-evoked symptoms or distention and discomfort threshold were not altered by R137696. A logistic regression model, characterizing the relationships between the volume and the visual analogue scale score for dyspeptic symptoms (nausea, fullness, discomfort, pain and satiety) as a sigmoidal curve, revealed that R137696 had no effect on distension-induced discomfort, fullness, pain and satiety compared to placebo. R137696 relaxes the gastric fundus in fasting conditions but has no effect on distension-evoked dyspeptic symptoms in healthy volunteers.

Paraneoplastic rhombencephalitis and brachial plexopathy in two cases of amphiphysin auto-immunity.

Amphiphysin, a synaptic vesicle protein, is an auto-immune target in rare cases of paraneoplastic neurological disorders. We report two additional cases with distinct neurological syndromes and paraneoplastic anti-amphiphysin antibodies. The first patient, a 59-year-old man, presented with cerebellar and cranial nerve dysfunction and small cell lung carcinoma. The second, a 77-year- old woman, presented with left brachial plexopathy followed by sensorimotor neuropathy and breast carcinoma.

Can bone marrow edema be seen on STIR images of the ankle and foot after 1 week of running?

PURPOSE: To evaluate whether initiation of running in sedentary individuals would lead to bone marrow edema on MR images, within the time span of 1 week. MATERIALS AND METHODS: The feet of 10 healthy volunteers were imaged by MR imaging before and after running during 30 min a day for 1 week. The images were evaluated by consensus of 2 musculoskeletal radiologists who graded the presence of bone marrow edema on a 4-point scale. Edema scores and number of bones involved before and after running were compared statistically. RESULTS: Edema was present on the baseline images in 3 subjects. After running edema showed an increase or was present in 5 subjects. The changes after running were statistically significant. Bones involved were the talus, calcaneus, navicular bone, cuboid bone, and 5th metatarsal. CONCLUSION: Edema patterns can be seen in the feet of asymptomatic individuals. During initiation of running an increase of edema or development of new edema areas can be seen.

Comparison of surface coil and knee coil for evaluation of the patellar cartilage by MR imaging.

PURPOSE: The aim of this work was to compare the knee coil and the surface coil for the visualisation of the patellar cartilage. MATERIALS AND METHODS: In 28 patients (17 women, 11 men) with an average age of 40 years (range 14-76) with knee pain MR was performed. Transverse images were obtained using a fast spin echo proton density weighted sequence on a Philips Gyroscan Intera 1.5 T clinical system. Transverse images were obtained at the level of the patellar cartilage using both the surface and the knee coil. All images were evaluated by consensus of two radiologists. They evaluated a number of quality criteria on a 4-point scale. Criteria for artefacts were also graded on a 4-point scale. RESULTS: For the visualisation of fluid there was no significant difference between the knee coil and the surface coil (P=0.021). For all other criteria regarding image quality and presence of imaging artefacts there was a significant difference between both coils (P<0.001) with the surface coil obtaining the better result. CONCLUSION: The use of the surface coil in the visualisation of the patellar cartilage can be recommended at knee MR.

Posterolateral supporting structures of the knee: findings on anatomic dissection, anatomic slices and MR images.

In this article we study the ligaments and tendons of the posterolateral corner of the knee by anatomic dissection, MR-anatomic correlation, and MR imaging. The posterolateral aspect of two fresh cadaveric knee specimens was dissected. The MR-anatomic correlation was performed in three other specimens. The MR images of 122 patients were reviewed and assessed for the visualization of different posterolateral structures. Anatomic dissection and MR-anatomic correlation demonstrated the lateral collateral, fabellofibular, and arcuate ligaments, as well as the biceps and popliteus tendons. On MR images of patients the lateral collateral ligament was depicted in all cases. The fabellofibular, arcuate, and popliteofibular ligaments were visualized in 33, 25, and 38% of patients, respectively. Magnetic resonance imaging allows a detailed appreciation of the posterolateral corner of the knee.

Severe adverse reactions with contrast agents for magnetic resonance: clinical experience in 30,000 MR examinations.

We report on the frequency, manifestations and reactions to gadolinium contrast media in patients who underwent MR imaging at our institution between 1988 and 1998. During a 10-year period 30,000 patients received an intravenous injection of 0.1 mmol/kg gadoterate meglumine or gadopentetate dimeglumine for an MRI examination. When a reaction occurred a written report was made (the events were categorized into mild, moderate, and severe). In the period of 10 years we obtained three reports of moderate or severe reactions to the administration of gadolinium. This paper discusses the safety issues of intravenous contrast media in MR imaging, focusing on two gadolinium complexes, gadoterate meglumine, gadopentetate dimeglumine.

MR imaging of the medial collateral ligament bursa: findings in patients and anatomic data derived from cadavers.

OBJECTIVE: The purpose of this work was to define the MR imaging findings of fluid collections confined to the medial collateral ligament (MCL) bursa and to correlate these findings with anatomic features shown in cadaveric specimens. MATERIALS AND METHODS: The anatomic location of the MCL bursa was investigated by MR-anatomic correlation in seven cadaveric knees. The MR imaging studies and clinical charts of six patients with fluid collections confined to the MCL bursa were reviewed. RESULTS: On anatomic sections, the MCL bursa was located between the superficial and deep portions of the MCL. Separate femoral and tibial compartments were seen in most specimens. CONCLUSION: The anatomy of the MCL bursa is shown with MR imaging in cadaveric specimens and patients. Understanding the compartmentlike distribution of fluid in the MCL bursa at MR imaging allows accurate diagnosis and differentiation from other conditions.

MR imaging of meniscal cysts: evaluation of location and extension using a three-layer approach.

PURPOSE: To analyze the extension of medial and lateral meniscal cysts relative to the capuloligamentous planes of the knee. MATERIALS AND METHODS: The MR images of 32 patients with meniscal cysts were reviewed. The location and extension of the meniscal cysts with reference to the capsule and ligaments were recorded. RESULTS: Most medial meniscal cysts were located posteromedially. Posteromedial meniscal cysts usually penetrated the capsule and were located between layer I and the fused layers II+III. From this site some extended anteriorly and then became located superficial to the superficial MCL. The location of lateral meniscal cysts was more varied. Anteriorly the cysts were located deep to the iliotibial band, whereas posterolateral cysts were located deep to the lateral collateral ligament. CONCLUSION: Although the site of capsular penetration of meniscal cysts is determined by the location of meniscal tears, the possible pathways of extension appear to be determined by the capsuloligamentous planes of the knee.

Three layers of the medial capsular and supporting structures of the knee: MR imaging-anatomic correlation.

The authors used a three-layer approach to correlate the appearance of the capsule and ligaments of the medial side of the knee on magnetic resonance (MR) images with corresponding anatomic slices. MR images of six fresh cadaveric specimens were obtained by using a proton-density-weighted fast spin-echo sequence with a 256 x 512 matrix. Specimens were frozen and sliced with a band saw into 3. 0-mm-thick sections that corresponded to the MR images. Three layers were depicted on both anatomic slices and MR images. Layer 1 consisted of the deep crural fascia; layer 2, the superficial portion of the medial collateral ligament (MCL); and layer 3, the capsule, the deep portion of the MCL, the meniscofemoral and meniscotibial extensions of the deep portion of the MCL, and the patellomeniscal ligament. Along the anterior aspect of the medial side of the knee, layer 1 was fused with layer 2; along the posterior aspect of the knee, layer 2 was fused with layer 3.

Calcific tendinitis of the longus colli muscle.

BACKGROUND: To the best of our knowledge, only one patient with calcium hydroxyapatite deposition disease (CHADD) of the longus colli muscle has been reported in the otolaryngology literature. METHODS: Clinical findings and results of imaging studies in such a patient are reported. RESULTS: Two particular imaging findings of this disorder are discussed. First, disappearance of calcifications over the short time frame of a week, accompanied by the resolution of clinical symptoms. Second, the presence of an extensive region of high signal intensity extending from the skull base to the lower border of C5, on T2-weighted spin-echo magnetic resonance (MR) images. CONCLUSIONS: Knowledge of the characteristic clinical spectrum and imaging features of this disorder are crucial for a correct diagnosis of this uncommon cause of odynophagia and dysphagia.

Cortical stimulation for central neuropathic pain: 3-D surface MRI for easy determination of the motor cortex.

Motor cortex electric stimulation has been reported to be effective for the treatment of central post-stroke pain and trigeminal neuropathic pain. Five patients with pain due to injury of the trigeminal nerve and with abnormalities of facial sensibility, as well as two patients suffering of a post-stroke thalamic pain, were subjected to stimulation applied epidurally on the motor cortex. Quadripolar electrodes were implanted under local anaesthesia and the precise location of the motor cortex was determined on three-dimensional surface MRI the day prior to surgery. In our experience, correct topographic localization of the electrode on the motor cortex seems to be crucial to obtain pain reduction.

Magnetic resonance imaging of the heart in a case of hepatocellular carcinoma extending into the right atrium.

Hepatocellular carcinoma is the most common primary malignant liver tumor occurring in more than 1 million cases a year all over the world. Vascular invasion is known to occur in 30% of patients at initial presentation [1]. An extension of the tumor into the right atrium is well described in the literature [2], with surgical resection as the only procedure available. But the diagnosis is often difficult before death. We report a case in which magnetic resonance imaging of liver and heart shows the extension of this tumor into the right atrium.

Sneddon's syndrome: a rare cause of diffuse vasculopathy. A case report with review of the literature.

We report a case of Sneddon's syndrome in a 39-year-old woman who developed recurrent cerebral ischaemic events associated with a livedo racemosa. We describe the clinical and radiological features of this rare vasculopathy. We also comment on the nosological place of the disorder and its possible association with antiphospholipid antibodies.