Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). CONCLUSION: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.

Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.

INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID. AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs. EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

Rare Adverse Events Associated with BNT162b2 mRNA Vaccine (Pfizer-BioNTech): A Review of Large-Scale, Controlled Surveillance Studies.

Given the increasing anti-vaccine movements erroneously touting vaccine danger, this review has investigated the rare adverse events potentially associated with BNT162b2 (Pfizer-BioNTech), an mRNA vaccine against the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Only real-world surveillance studies with at least 0.1 million BNT162b2-vaccinated participants and one unvaccinated control group were selected for review. A total of 21 studies examining the potential association of BNT162b2 with cardiovascular, herpetic, thrombotic or thrombocytopenic, neurological, mortality, and other miscellaneous rare adverse events were described in this review. Only myocarditis is consistently associated with BNT162b2. An unclear direction of association was seen with stroke (hemorrhagic and ischemic), herpes zoster, and paresthesia from BNT162b2, which may require more studies to resolve. Fortunately, most surveillance studies detected no increased risks of the remaining rare adverse events reviewed herein, further reassuring the safety of BNT162b2. In conclusion, this review has concisely summarized the current rare adverse events related and unrelated to BNT162b2, arguably for the first time in sufficient depth, to better communicate vaccine safety to the public.

Contrast-enhanced magnetic resonance imaging perfusion can predict microvascular invasion in patients with hepatocellular carcinoma (between 1 and 5 cm).

PURPOSE: To evaluate the role of perfusion parameters with MR imaging of the liver in diagnosing MVI in hepatocellular carcinoma (HCC) (between 1 and 5 cm). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. In 80 patients with 43 MVI( +) and 42 MVI( -) HCC, whole-liver perfusion MR imaging with Cartesian k-space undersampling and compressed sensing reconstruction was performed after injection of 0.1 mmol/kg gadopentetate dimeglumine. Parameters derived from a dual-input single-compartment model of arterial flow (Fa), portal venous flow (Fp), total blood flow (Ft = Fa + Fp), arterial fraction (ART), distribution volume (DV), and mean transit time (MTT) were measured. The significant parameters between the two groups were included to correlate with the presence of MVI at simple and multiple regression analysis. RESULTS: In MVI-positive HCC, Fp was significantly higher than in MVI-negative HCC, whereas the reverse was seen for ART (p < 0.001). Tumor size (ß = 1.2, p = 0.004; odds ratio, 3.20; 95% CI 1.45, 7.06), Fp (ß = 1.1, p = 0.004; odds ratio, 3.09; 95% CI 1.42, 6.72), and ART (ß = - 3.1, p = 0.001; odds ratio, 12.13; 95% CI 2.85, 51.49) were independent risk factors for MVI. The AUC value of the combination of all three metrics was 0.931 (95% CI 0.855, 0.975), with sensitivity of 97.6% and specificity of 76.2%. CONCLUSION: The combination of Fp, ART, and tumor size demonstrated a higher diagnostic accuracy compared with each parameter used individually when evaluating MVI in HCC (between 1 and 5 cm).

Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients.

BACKGROUND: Cancer cachexia is a clinical manifestation in various advanced cancers that characterized by muscle atrophy and fat loss as its main features; it is frequently associated with systemic inflammatory response. However, the differences in inflammatory response and lipid metabolism of different genders remain unclear. This study explores the difference between cachexic and non-cachexic patients in different genders and cancer types and focus on the plasma inflammation factors levels and lipid metabolism parameters in different genders. METHODS: We first analyzed the general characteristics in 311 cancer patients between cachexic and non-cachexic patients, with an emphasis on expression levels related to inflammatory factors and lipid metabolism parameters. We then further analyzed these characteristics in different genders and cancer types. Lastly, the correlations between plasma interleukin-6 (IL-6) and lipid metabolism parameters in cachexia patients of different genders were analyzed. RESULTS: Among 311 patients, there were 74 cancer cachexia patients (50 males and 24 females) and 237non-cachexia patients (150 males and 87 females). Body mass index (BMI), TNM stage, plasma concentration of hemoglobin, platelet, lymphocyte count, total protein, albumin, prealbumin, total cholesterol, apolipoprotein E (ApoE), free fatty acid (FFA) and IL-6 were significantly different between cachexic and non-cachexic patients (all p < 0.05). In addition, these characteristics were different in different cancer types. When compared to male non-cachexic patients, male cachexic patients showed a significant increase in plasma levels of IL-6 and platelet, later TNM stage, with marked decrease in their plasma total protein, albumin, prealbumin, ApoE as well as their lymphocyte counts and hemoglobin levels (all p < 0.05). In comparison with female non-cachexic patients, female cachexic patients' IL-6 levels and FFA were significantly elevated with noticeable decrease in their BMI, total cholesterol, ApoE and prealbumin, as well as later TNM stage (all p < 0.05). Correlation analysis revealed that IL-6 levels in female cachexic patients had a significant positive correlation with FFA expression, but this correlation not reflected in male patients. CONCLUSION: This study demonstrates the different metabolic characteristics of male and female cancer cachexia patients. Future study about cancer cachexia should pay attention to different genders and cancer types.

The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes).

Diabetes mellitus is seen to be prevalent among the different epidemics. The prevalence rate of the diabetes mellitus is seen to be increasing in different regions of the world. Type 2 diabetes mellitus is the most common form of the disease that causes the defect in the production of insulin. It is associated with the disruption in the metabolism of fat, proteins and carbohydrates. Different complications that are associated with T2DM includes the retinopathy, neuropathy, nephropathy and weakness and other issues. Due to the loss of the function of the insulin, the metabolism is disturbed. . It is needed to consider the effects of inflammation aging and the oxidative stress on the diabetes mellitus. Therefore this review has dealt with this particular issue in great detail. The predominant aim of this review was to evaluate the effects of inflammation aging and oxidative stress on the T2DM. It was achieved through correlating and comparing the studies of different researchers. This review article has reviewed this topic in great detail considering the different researches related to the inflammation aging, oxidative stress and their impact on the diabetes mellitus.

Early symptom non-improvement and aggravation are associated with the treatment response to SSRIs in MDD: a real-world study.

PURPOSE: Early improvement in major depressive disorder is defined as a reduction of ≥20% in the 17-item Hamilton Depression Rating Scale (HAM-D-17) score at the second week after initiation of treatment, predicting long-term treatment response. However, there remains no effective strategy for switching medications when a patient fails to reach early improvement at the second week. This study focused on the predictive value of early symptom changes in each item of the HAM-D-17 scale for treatment response to selective serotonin reuptake inhibitor (SSRI) monotherapy and to provide a reference for switching antidepressants to enhance early treatment efficacy. PATIENTS AND METHODS: Our study was an observational, real-world study that enrolled 90 treatment-naïve patients experiencing their first episode of major depressive disorder in the outpatient department of Huashan Hospital. Patients who did not achieve the threshold of early improvement in the second week after starting treatment were switched to alternative SSRI monotherapy. Patient follow-up occurred at 2, 4, 8, and 12 weeks after the initiation of treatment. We analyzed the relationship between the change in each symptom on the HAM-D-17 scale and treatment efficacy. RESULTS: Early improvement predicted the treatment response at 12 weeks (χ 2=19.249, P<0.001), whereas early non-improvement in insomnia and anxiety was associated with a poor response (OR =9.487, 95% CI: 1.312-68.588 and OR =12.947, 95% CI: 1.99-82.246, respectively). At week 2, general somatic symptom aggravation was associated with a poorer response (OR =73.337, 95% CI: 2.232->999.999); treatment-emergent headache and tremor were associated with treatment efficacy (t=-9.521, P<0.001 and t=3.660, P=0.001, respectively). In addition, the increase in suicidal thoughts, once treatment began, had no relationship with the treatment response (OR =0.821, P=0.872). CONCLUSION: This study suggested that patients with early non-improvement in insomnia and anxiety were not suitable for switches in SSRI monotherapy. Patients with treatment-emergent symptoms, especially headaches and tremors, were not suitable for switching from monotherapy to another SSRI.

Pre-TACE kurtosis of ADCtotal derived from histogram analysis for diffusion-weighted imaging is the best independent predictor of prognosis in hepatocellular carcinoma.

PURPOSE: To determine the feasibility of pre-TACE IVIM imaging based on histogram analysis for predicting prognosis in the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five patients prospectively underwent 1.5T MRI 1 week before TACE. Histogram metrics for IVIM parameters and ADCs maps between responders and non-responders with mRECIST assessment were compared. Kaplan-Meier, log-rank tests and Cox proportional hazard regression model were used to correlate variables with time to progression (TTP). RESULTS: Mean (p = 0.022), median (p = 0.043), and 25th percentile (p < 0.001) of perfusion fraction (PF), mean (p < 0.001), median (p < 0.001), 25th percentile (p < 0.001) and 75th percentile (p = 0.001) of ADC(0,500), mean (p = 0.005), median (p = 0.008) and 25th percentile (p = 0.039) of ADCtotal were higher, while skewness and kurtosis of PF (p = 0.001, p = 0.005, respectively), kurtosis of ADC(0,500) and ADCtotal (p = 0.005, p = 0.001, respectively) were lower in responders compared to non-responders. Multivariable analysis demonstrated that mRECIST was associated with TTP independently, and kurtosis of ADCtotal had the best predictive performance for disease progression. CONCLUSION: Pre-TACE kurtosis of ADCtotal is the best independent predictor for TTP. KEY POINTS: • mRECIST was associated with TTP independently. • Lower kurtosis and higher mean for ADCs tend to have good response. • Pre-TACE kurtosis of ADC total is the best independent predictor for TTP.