Structural alterations of the choroid evaluated using enhanced depth imaging optical coherence tomography in patients with coronavirus disease.

PURPOSE: To assess choroidal changes using enhanced depth imaging optical coherence tomography in coronavirus disease (COVID-19). METHODS: Thirty-two patients with moderate COVID-19 and 34 healthy subjects were included in the study. Choroidal thickness was measured at 3 points as follows: at the subfovea, 1500 mm nasal to the fovea, and 1500 mm temporal to the fovea. The total choroidal area, luminal area, stromal area, and choroidal vascular index were measured with Image-J. All the measurements were performed during the disease and at 4 months after remission. RESULTS: In the patient group, the subfoveal, nasal, and temporal choroidal thicknesses were decreased as compared with those in the controls, but without statistically significant differences (p=0.534, p=0.437, and p=0.077, respectively). The mean total choroidal, stromal, and luminal areas and choroidal vascular index were statistically significantly decreased in the patient group (p<0.001, p=0.001, p=0.001, and p=0.003; respectively). At 4 months after remission, the choroidal structural parameters and choroidal vascular index revealed statistically significant increases as compared with the baseline measurements in the patients with COVID-19 (all p<0.001 and p=0.047, respectively). CONCLUSION: The choroidal vascular and stromal parameters showed significant transient decreases during the disease course of COVID-19.

Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors.

BACKGROUND: acute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients. METHODS: cross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality. RESULTS: two hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 - 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004). DISCUSSION: we described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.

Influence of Covid-19 infection on fetal thymus size after recovery.

OBJECTIVES: To investigate the long-term effects of the SARS-CoV-2 infection on the fetal immune system by fetal thymus size measurements with ultrasound (USG). METHODS: This prospective study was conducted in the Turkish Ministry of Health Ankara City Hospital between November 1, 2020 and April 1, 2021, with recovered, pregnant women, four weeks after they had been confirmed for the SARS-CoV-2 infection by real-time polymerase-chain-reaction (RT-PCR). COVID-19 recovered (CR) pregnant women compared with age-matched pregnant controls in terms of demographic features, fetal thymic-thoracic ratio (TTR), and laboratory parameters. RESULTS: There was no difference in demographic features between the two groups. TTR found significantly lower in the CR group than the control group (p=0.001). The fetal TTR showed a significant and moderate correlation with maternal monocyte counts, monocyte to lymphocyte ratio (MLR), and red cell distribution width (RDW); while it did not correlate with lymphocyte counts, c-reactive protein (CRP), and procalcitonin levels. CONCLUSIONS: The 2019 novel coronavirus disease (COVID-19) reduces fetal thymus size in pregnant women with mild or moderate symptoms after recovery from the infection.

Comparison of the short-term outcomes of using DST and PPH staplers in the treatment of grade III and IV hemorrhoids.

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case-control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.

An updated review of teriflunomide's use in multiple sclerosis.

Teriflunomide, a once daily, oral disease-modifying therapy, has demonstrated consistent efficacy, safety and tolerability in patients with relapsing forms of multiple sclerosis (MS) and with a first clinical episode suggestive of MS treated up to 12 years. This review is an update to a previous version that examined data from the teriflunomide core clinical development program and extension studies. Data have since become available from active comparator trials with other disease-modifying therapies, treatment-related changes in brain volume (analyzed using structural image evaluation using normalization of atrophy) and real-world evidence including patient-reported outcomes. Initial data on the potential antiviral effects of teriflunomide in patients with MS, including case reports of patients infected with the 2019 novel coronavirus (SARS-CoV-2), are also presented.

Lay abstract Teriflunomide, a treatment taken orally once a day, has shown consistent effectiveness and safety in patients with relapsing forms of multiple sclerosis (MS). This review is an update to a previous version that summarized the trials from when teriflunomide was in clinical development for MS. Some of the newer studies described here compared teriflunomide with other MS treatments. Studies have shown positive effects of teriflunomide on brain volume; teriflunomide may also be effective against some viruses. People taking teriflunomide generally report stable cognition and quality of life, with no worsening of fatigue or disability. In the EU, teriflunomide has been recently approved for use in pediatric patients 10 years of age and above.

Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients.

BACKGROUND: COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. METHODS: Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. RESULTS: Of the enrolled patients (median age 66 years [IQR: 59-74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24-31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). CONCLUSIONS: Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.

Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID-19: a cohort study.

OBJECTIVE: To investigate the optic nerve and macular parameters of children who recovered from COVID-19 compared with healthy children using optical coherence tomography (OCT). DESIGN: Cohort study. SETTING: Hospital Clinico San Carlos, Madrid. PATIENTS: Children between 6 and 18 years old who recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection and historical controls were included. INTERVENTIONS: All patients underwent an ophthalmological examination, including macular and optic nerve OCT. Demographic data, medical history and COVID-19 symptoms were noted. MAIN OUTCOME MEASURES: Peripapillary retinal nerve fibre layer thickness, macular retinal nerve fibre layer thickness, macular ganglion cell layer thickness and retinal thickness. RESULTS: 90 patients were included: 29 children who recovered from COVID-19 and 61 controls. Patients with COVID-19 presented an increase in global peripapillary retinal nerve fibre layer thickness (mean difference 7.7; 95% CI 3.4 to 12.1), temporal superior (mean difference 11.0; 95% CI 3.3 to 18.6), temporal inferior (mean difference 15.6; 95% CI 6.5 to 24.7) and nasal (mean difference 9.8; 95% CI 2.9 to 16.7) sectors. Macular retinal nerve fibre layer analysis showed decreased thickness in the nasal outer (p=0.011) and temporal inner (p=0.036) sectors in patients with COVID-19, while macular ganglion cell layer thickness increased in these sectors (p=0.001 and p=0.015, respectively). No differences in retinal thickness were noted. CONCLUSIONS: Children with recent history of COVID-19 present significant changes in peripapillary and macular OCT analyses.

Changes in olfactory bulbus volume and olfactory sulcus depth in the chronic period after COVID-19 infection.

BACKGROUND: Although there are a limited number of studies investigating the changes in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD) values in the acute and subacute periods after COVID-19 infection, there are no studies conducted in the chronic period. PURPOSE: The aim of this study is to reveal the changes in OBV and OSD after COVID-19 in the chronic period. MATERIAL AND METHODS: A total of 83 people were included in our study, including 42 normal healthy individuals (control group) and 41 patients with COVID-19 infection (10-12 months after infection). RESULTS: The COVID-19 group included 41 patients with the mean age 40.27 ± 14.5 years and the control group included 42 individuals with the mean age 40.27 ± 14.4. The mean OBV was 67.97 ± 14.27 mm3 in the COVID-19 group and 94.21 ± 7.56 mm3 in the control group. The mean OSD was 7.98 ± 0.37 mm in the COVID-19 group and 8.82 ± 0.74 mm in the control group. Left, right, and mean OBVs and OSD were significantly lower in patients with COVID- 19 than the control individuals (all p < .05). CONCLUSION: Our findings show that COVID-19 infection causes a significant decrease in the OBV and OSD measurements in the chronic period.

Radiological measurement of cochlear dimensions in cochlear hypoplasia and its effect on cochlear implant selection.

OBJECTIVE: To determine the effect of cochlear dimensions on cochlear implant selection in cochlear hypoplasia patients. METHODS: Temporal bone computed tomography images of 36 patients diagnosed with cochlear hypoplasia between 2010 and 2016 were retrospectively reviewed and compared with those of 40 controls without sensorineural hearing loss. RESULTS: Basal turn length and mid-modiolar height were significantly lower in the cochlear hypoplasia patients with subtypes I, II and III than in the control group (p < 0.001). Mid-scalar length was significantly shorter in subtype I-III patients as compared with the control group (p < 0.001). In addition, cochlear canal length (measured along the lateral wall) was significantly shorter in subtype I-IV patients than in the control group (subtypes I-III, p < 0.001; subtype IV, p = 0.002). CONCLUSION: Cochlear hypoplasia should be considered if basal turn length is less than 7.5 mm and mid-modiolar height is less than 3.42 mm. The cochlear implant should be selected according to cochlear hypoplasia subgroup. It is critically important to differentiate subtype II from incomplete partition type I and subtype III from a normal cochlea, to ensure the most appropriate implant electrode selection so as to optimise cochlear implantation outcomes.

Brain volumetric changes in the general population following the COVID-19 outbreak and lockdown.

The coronavirus disease 2019 (COVID-19) outbreak introduced unprecedented health-risks, as well as pressure on the economy, society, and psychological well-being due to the response to the outbreak. In a preregistered study, we hypothesized that the intense experience of the outbreak potentially induced stress-related brain modifications in the healthy population, not infected with the virus. We examined volumetric changes in 50 participants who underwent MRI scans before and after the COVID-19 outbreak and lockdown in Israel. Their scans were compared with those of 50 control participants who were scanned twice prior to the pandemic. Following COVID-19 outbreak and lockdown, the test group participants uniquely showed volumetric increases in bilateral amygdalae, putamen, and the anterior temporal cortices. Changes in the amygdalae diminished as time elapsed from lockdown relief, suggesting that the intense experience associated with the pandemic induced transient volumetric changes in brain regions commonly associated with stress and anxiety. The current work utilizes a rare opportunity for real-life natural experiment, showing evidence for brain plasticity following the COVID-19 global pandemic. These findings have broad implications, relevant both for the scientific community as well as the general public.

Ciclesonide activates glucocorticoid signaling in neonatal rat lung but does not trigger adverse effects in the cortex and cerebellum.

Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections.

[Ultrasound in the management of the critically ill patient with SARS-CoV-2 infection (COVID-19): narrative review]. / Ecografía en el manejo del paciente crítico con infección por SARS-CoV-2 (COVID-19): una revisión narrativa.

The clinical picture of SARS-CoV-2 infection (COVID-19) is characterized in its more severe form, by an acute respiratory failure which can worsen to pneumonia and acute respiratory distress syndrome (ARDS) and get complicated with thrombotic events and heart dysfunction. Therefore, admission to the Intensive Care Unit (ICU) is common. Ultrasound, which has become an everyday tool in the ICU, can be very useful during COVID-19 pandemic, since it provides the clinician with information which can be interpreted and integrated within a global assessment during the physical examination. A description of some of the potential applications of ultrasound is depicted in this document, in order to supply the physicians taking care of these patients with an adapted guide to the intensive care setting. Some of its applications since ICU admission include verification of the correct position of the endotracheal tube, contribution to safe cannulation of lines, and identification of complications and thrombotic events. Furthermore, pleural and lung ultrasound can be an alternative diagnostic test to assess the degree of involvement of the lung parenchyma by means of the evaluation of specific ultrasound patterns, identification of pleural effusions and barotrauma. Echocardiography provides information of heart involvement, detects cor pulmonale and shock states.

Artificial intelligence matches subjective severity assessment of pneumonia for prediction of patient outcome and need for mechanical ventilation: a cohort study.

To compare the performance of artificial intelligence (AI) and Radiographic Assessment of Lung Edema (RALE) scores from frontal chest radiographs (CXRs) for predicting patient outcomes and the need for mechanical ventilation in COVID-19 pneumonia. Our IRB-approved study included 1367 serial CXRs from 405 adult patients (mean age 65 ± 16 years) from two sites in the US (Site A) and South Korea (Site B). We recorded information pertaining to patient demographics (age, gender), smoking history, comorbid conditions (such as cancer, cardiovascular and other diseases), vital signs (temperature, oxygen saturation), and available laboratory data (such as WBC count and CRP). Two thoracic radiologists performed the qualitative assessment of all CXRs based on the RALE score for assessing the severity of lung involvement. All CXRs were processed with a commercial AI algorithm to obtain the percentage of the lung affected with findings related to COVID-19 (AI score). Independent t- and chi-square tests were used in addition to multiple logistic regression with Area Under the Curve (AUC) as output for predicting disease outcome and the need for mechanical ventilation. The RALE and AI scores had a strong positive correlation in CXRs from each site (r2 = 0.79-0.86; p < 0.0001). Patients who died or received mechanical ventilation had significantly higher RALE and AI scores than those with recovery or without the need for mechanical ventilation (p < 0.001). Patients with a more substantial difference in baseline and maximum RALE scores and AI scores had a higher prevalence of death and mechanical ventilation (p < 0.001). The addition of patients' age, gender, WBC count, and peripheral oxygen saturation increased the outcome prediction from 0.87 to 0.94 (95% CI 0.90-0.97) for RALE scores and from 0.82 to 0.91 (95% CI 0.87-0.95) for the AI scores. AI algorithm is as robust a predictor of adverse patient outcome (death or need for mechanical ventilation) as subjective RALE scores in patients with COVID-19 pneumonia.

Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters.

Olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (COVID-19). Information on the damage and repair of the neuroepithelium and its impact on olfactory function after COVID-19 is still incomplete. While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the ongoing worldwide outbreak of COVID-19, little is known about the changes triggered by SARS-CoV-2 in the olfactory epithelium (OE) at the cellular level. Here, we report profiles of the OE after SARS-CoV-2 infection in golden Syrian hamsters, which is a reliable animal model of COVID-19. We observed severe damage in the OE as early as 3 days postinoculation and regionally specific damage and regeneration of the OE within the nasal cavity; the nasal septal region demonstrated the fastest recovery compared to other regions in the nasal turbinates. These findings suggest that anosmia related to SARS-CoV-2 infection may be fully reversible.

Pulmonary thrombosis in Covid-19: before, during and after hospital admission.

Disordered coagulation, endothelial dysfunction, dehydration and immobility contribute to a substantially elevated risk of deep venous thrombosis, pulmonary embolism (PE) and systemic thrombosis in coronavirus disease 2019 (Covid-19). We evaluated the prevalence of pulmonary thrombosis and reported RV (right ventricular) dilatation/dysfunction associated with Covid-19 in a tertiary referral Covid-19 centre. Of 370 patients, positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 39 patients (mean age 62.3 ± 15 years, 56% male) underwent computed tomography pulmonary angiography (CTPA), due to increasing oxygen requirements or refractory hypoxia, not improving on oxygen, very elevated D-dimer or tachycardia disproportionate to clinical condition. Thrombosis in the pulmonary vasculature was found in 18 (46.2%) patients. However, pulmonary thrombosis did not predict survival (46.2% survivors vs 41.7% non-survivors, p = 0.796), but RV dilatation was less frequent among survivors (11.5% survivors vs 58.3% non-survivors, p = 0.002). Over the following month, we observed four Covid-19 patients, who were admitted with high and intermediate-high risk PE, and we treated them with UACTD (ultrasound-assisted catheter-directed thrombolysis), and four further patients, who were admitted with PE up to 4 weeks after recovery from Covid-19. Finally, we observed a case of RV dysfunction and pre-capillary pulmonary hypertension, associated with Covid-19 extensive lung disease. We demonstrated that pulmonary thrombosis is common in association with Covid-19. Also, the thrombotic risk in the pulmonary vasculature is present before and during hospital admission, and continues at least up to four weeks after discharge, and we present UACTD for high and intermediate-high risk PE management in Covid-19 patients.