A healthy 35 year-old man who had visited Wuhan, China, presented with cough and fever that progressed to pneumonia. This report describes the diagnosis, clinical course, and management of the ...condition. The case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels.
Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients ...confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously
. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Several diseases may cause craniovertebral instability warranting occiput-cervical fusion. As occipital screw and rod constructs are becoming more popular, requiring that screws be placed either ...medially or laterally in the occipital bone, the need for clearer anatomical and computed tomography (CT)-confirmed data regarding the relative thickness of the occiput in its various localities has become more critical. In 18 cadaveric specimens, the occipital bone was divided into 35 measurable segments. Transversely, the occipital bone was divided into five lines starting at the level of the inion; horizontal lines then proceeded inferiorly in 1-cm segments, 1, 2, 3, and 4 cm below the level of inion. In a comparable fashion, the occipital bone was divided vertically, starting at the midline, and proceeding laterally also in 1-, 2-, and 3-cm segments. Anatomical measurements of thickness were directly performed using a Vernier caliper. Results were directly correlated with axial CT measurements of bony thickness. Anatomical and CT measurements closely correlated within the same specimen, but there was significant interspecimen variability. The marked differences in the occipital bone anatomy noted between specimens indicates that patients undergoing occipital screw placement for cranial-cervical instability would benefit from preoperative occipital CT evaluations.
The immobilization strategy can promote greater enzyme utilization in applications by improving the overall stability and reusability of the enzyme. In this work, the L-asparaginase (L-ASNase) ...obtained from
Escherichia coli
was chosen as a model enzyme and immobilized onto the Fe
3
O
4
@Au-carboxymethyl chitosan (CMC) magnetic nanoparticles (MNPs) through adsorption. TEM, SEM, FT-IR, XRD, EDS, and TGA analyses were performed to examine the structure with and without L-ASNase. The yield of immobilized L-ASNase on Fe
3
O
4
@Au-CMC was found to be 68%. The biochemical properties such as optimum pH, optimum temperature, reusability, and thermal stability of the Fe
3
O
4
@Au-CMC/L-ASNase were comprehensively investigated. For instance, Fe
3
O
4
@Au-CMC/L-ASNase reached maximum activity at pH 7.0 and the optimum temperature was found to be 50 °C. The noticeably lower Ea value of the Fe
3
O
4
@Au-CMC/L-ASNase revealed the enhanced catalytic activity of this enzyme after immobilization. The
Km
and
Vmax
values were 3.27 ± 0.48 mM, and 51.54 ± 0.51 μmol min
−1
for Fe
3
O
4
@Au-CMC/L-ASNase, respectively, which means good substrate affinity. The Fe
3
O
4
@Au-CMC/L-ASNase retained 65% of its initial activity even after 90 min at 60 °C. Moreover, it maintained more than 75% of its original activity after 10 cycles, indicating its excellent reusability. The results obtained suggested that this investigation highlights the use of MNPs as a support for the development of more economical and sustainable immobilized enzyme systems.
Although numerous studies have investigated the neurotrophic factors and hippocampal activity in posttraumatic stress disorder (PTSD) separately each other, it is unclear whether an association ...between neurotrophic factors and hippocampal activity is present. The aim of this study was to evaluate the functional changes in hippocampus before and after treatment with escitalopram and to associate these changes with peptides related to neuronal growth in patients with chronic PTSD and trauma survivors without PTSD. Fifteen earthquake survivors with chronic PTSD and thirteen drug naïve trauma exposed individuals without PTSD underwent fMRI scans in a block design. Serum levels of Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) were measured before and after 12 weeks treatment with escitalopram. Baseline median serum level of NGF was significantly lower in patients with chronic PTSD than trauma survivors; however, 12 weeks of treatment with escitalopram significantly increased it. Higher activation was found both in left and right hippocampus for chronic PTSD group than trauma survivors. Treatment with escitalopram was significantly associated with suppression of the hyperactivation in left hippocampus in patients with chronic PTSD. Bilateral hyperactivation in hippocampus and lowered NGF may associate with neurobiological disarrangements in chronic PTSD. Treatment with escitalopram was significantly associated with both improvement in the severity of PTSD symptoms and biological alterations. Patients diagnosed with PTSD may have further and complicated deteriorations in hippocampal networks and neurotransmitter systems than individuals who had not been diagnosed with PTSD following the same traumatic experience.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was ...modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important.
Patients and methods
In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan–Meier method. OS was estimated by using the Kaplan–Meier method.
Results
The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (
p
= 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (
p
= 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio HR = 1.9;
p
= 0.04}, ECOG PS ≥ 1 (HR = 2.7;
p
= 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8;
p
< 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39;
p
< 0.001) maintained a significant association with OS in multivariate analysis.
Conclusions
Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients’ use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a ...good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.
This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18–59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.
Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 65·1% in the vaccine group and 3568 34·9% in the placebo group) and the per protocol group consisted of 10 029 participants (6559 65·4% and 3470 34·6%) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36–48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases 14·6–59·3 per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases 135·7–261·1 per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4–92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 8·2% participants in the vaccine group and 248 7·0% the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 2·4% in the vaccine group and 40 1·1% in the placebo group, p<0·0001).
CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.
Health Institutes of Turkey (TUSEB).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Serum Zonulin Levels in Pediatric Migraine Öz Tunçer, Gökçen; Akbaş, Yılmaz; Köker, Alper ...
Pediatric neurology,
July 2023, 2023-Jul, 2023-07-00, 20230701, Volume:
144
Journal Article
Peer reviewed
Migraine is a complex neurogenic inflammatory disorder. There are strong neuronal, endocrine, and immunologic connections between the brain and gastrointestinal system. Damage to the intestinal ...barrier is thought to cause systemic immune dysregulation. Zonulin is a protein produced by the small intestine epithelium in humans that regulates intestinal permeability through intracellular tight junctions and is a potential marker for inflammation. Zonulin increases in positive correlation with permeability. In our study, we aimed to research the correlation between serum zonulin levels in the period between attacks in pediatric patients with migraine.
The study included 30 patients with migraine and 24 healthy controls, matched in terms of sex and age. Demographic and clinical characteristics were recorded. Serum zonulin levels were studied with the enzyme-linked immunosorbent assay method.
Patients had a mean of 5.6 ± 3.5 attacks per month. The mean serum zonulin was 5.68 ± 1.21 ng/mL in the migraine group and 5.72 ± 2.1 ng/mL in the control group with no significant difference found (P = 0.084). In the migraine group, no correlations were identified between serum zonulin levels and age, body mass index, pain frequency, pain duration, onset time, visual analog scale score, and presence of gastrointestinal systems apart from nausea-vomiting.
More than 50 proteins were identified to affect the intestinal permeability apart from zonulin. There is a need for prospective studies encompassing the time of attack, but our study is important as it is the first study about zonulin levels in pediatric migraine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
This study aims to investigate the prognostic value of the systemic immune-inflammation index (SII)and its impact on survival in patients with metastatic renal cell carcinoma (mRCC). A total ...of 706patients with mRCC treated with tyrosine kinase inhibitors (TKIs)between January 2007 and June 2020 (i.e., sunitinib, pazopanib) were included in this study. SII was calculated in 621 patients with the following formula:neutrophil (cellsx10
9
/L) x platelet (cellsx10
9
/L) / lymphocyte (cellsx10
9
/L).All patients were classified into SII-high and SII-low groups based on the cut-off value of SII at 756, which was the median SII level of our study group. The minimal follow-up duration was 10 months in all cohorts. The median age of patients was 60 (interquartile range (IQR):53–67) years. Three out of four patients were male. The majority of patients (85.7%) had clear cell histology, and sarcomatoid differentiation was observed in 16.9% of all patients. There were 311 and 310 patients in the SII-low and SII-high groups, respectively. In general, baseline characteristics were similar in each group. However, the rate of patients treated with sunitinib (63.3% vs. 49.0%,
p
< 0.001) and those who underwent nephrectomy (83.6% vs. 64.2%,
p
< 0.001) was higher in the SII-low group than in the SII-high group. On the other hand, patients with the IMDC poorrisk (31.6% vs. 8.0%,
p
< 0.001), those with bone (51.8% vs. 32.2%,
p
< 0.001) or central nervous system (12.9% vs. 5.8%,
p
= 0.026) metastasis, and those with Eastern Cooperative Oncology Group(ECOG) 2–4 performance score (28.1% vs.17.7%,
p
= 0.002) were more common in the SII-high group than in the SII-low group. The median overall survival (OS) was longer in the SII-low group than in the SII-high group (34.6 months vs. 14.5 months,
p
< 0.001). Similarly, the median progression-free survival (PFS) was longer in the SII-low group than in the SII-high group (18.0 months vs. 7.7 months,
p
< 0.001).In multivariableanalysis, SII was an independent prognostic factor for OS (hazard ratio (HR):1.39, 95% confidence interval (CI):1.05–1.85,
p
= 0.01) and PFS (HR:1.60, 95% CI:1.24–2.05,
p
< 0.001).Pre-treatment level of high SII might be considered a predictor of poor prognosisin patients with mRCC treated with TKIs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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