Sunday, August 21, 2022

COVID-19 severity and risk of subsequent cardiovascular events

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Abstract
Background
Little is known about the relationship between COVID-19 severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of US adults.
Methods
Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between April 1, 2020 and May 31, 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 d ays after COVID-19 diagnosis using inverse probability of treatment weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only.
Results
1,357,518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [HR]: 1.80 [95%CI: 1.71−1.89]) or non-ICU hospitalization (HR: 1.28 [1.24−1.33]). Risk of subsequent hospitalization for CVE was even higher (HR: 3.47 [3.20–3.76] for ICU and HR: 1.96 [1.85–2.09] for non-ICU hospitalized vs. outpatient only).
Conclusions
COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder C OVID-19 who were managed solely in the outpatient setting even after adjusting for differences between these groups. These findings underscore the continued importance of preventing SARS-CoV-2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.
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Nephrotoxicity of Vancomycin in Combination with Beta-lactam Agents: Ceftolozane-tazobactam vs. Piperacillin-tazobactam

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Abstract
Background
Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactam (BL) such as piperacillin-tazobactam (TZP) but not had been evaluated with ceftolozane-tazobactam (C/T). We aim to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared to VAN in combination to TZP (VAN-TZP).
Method
We conducted a multi-center observational comparative study across the United States. The p rimary analysis was a composite outcome of AKI: 1) RIFLE, 2) AKIN, or 3) VAN-induced-nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis had been conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time-to-nephrotoxicity between the two groups.
Results
We included (n = 90) VAN/C/T and (n = 284) VAN-TZP at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs. 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = 0.011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with patients receiving VAN-C/T; with an aOR of 3.308 [1.560-6.993]. Results of the stratified Kaplan-Meir with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients receiving VAN-TZP (P = 0.004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = 0.001).
Conclusions
Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to the piperacillin which is a component in the VAN-TZP combination but not the VAN-C/T.
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Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19

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Abstract
Background
Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear.
Methods
We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed C ovid-19 between December 1, 2021, and April 18, 2022, were included. Cohorts were developed based on the use of NMV-r within five days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-days follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, Covid-19 associated complications, and diagnostic test utilization.
Results
After propensity score matching, 1,130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort as compared to 163 (14.4%) patients in the non-NMV-r cohort (OR 0.5, CI 0.39-0.67; p<0.005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing were noted in NM V-r treated patients. There was no apparent increase serious complications between days 10 to 30.
Conclusion
Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.
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Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification

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Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification

We developed a machine learning model using a feature selection data input that was able to reliably predict oral cancer recurrence within 1-year intervals. Precise modeling of timing of recurrence can help personalize surveillance protocols to enhance early detection and reduce extraneous healthcare costs.


Objective(s)

We aimed to develop a machine learning (ML) model to accurately predict the timing of oral squamous cell carcinoma (OSCC) recurrence across four 1-year intervals.

Methods

Patients with surgically treated OSCC between 2012–2018 were retrospectively identified from the Yale-New Haven Health system tumor registry. Patients with known recurrence or minimum follow-up of 24 months from surgery were included. Patients were classified into one of five levels: four 1-year intervals and one level for no recurrence (within 4 years of surgery). Three sets of data inputs (comprehensive, feature selection, nomogram) were combined with 4 ML architectures (logistic regression, decision tree (DT), support vector machine (SVM), artificial neural network classifiers) yielding 12 models in total. Models were primarily evaluated using mean absolute error (MAE), lower values indicating better prediction of 1-year interval recurrence. Secondary outcomes included accuracy, weighted precision, and weighted recall.

Results

389 patients met inclusion criteria: 102 (26.2%) recurred within 48 months of surgery. Median follow-up time was 25 months (IQR: 15–37.5) for patients with recurrence and 44 months (IQR: 32–57) for patients without recurrence. MAE of 0.654% and 80.8% accuracy were achieved on a 15-variable feature selection input by 2 ML models: DT and SVM classifiers.

Conclusions

To our knowledge, this is the first study to leverage multiclass ML models to predict time to OSCC recurrence. We developed a model using feature selection data input that reliably predicted recurrence within 1-year intervals. Precise modeling of recurrence timing has the potential to personalize surveillance protocols in the future to enhance early detection and reduce extraneous healthcare costs.

Level of Evidence

III Laryngoscope, 2022

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Long‐term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

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Long-term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

Premature infants undergoing patent ductus arteriosus ligation are at risk for vocal fold paralysis leading to long term voice and swallowing complications. In this study, we review risk factors for vocal fold paralysis and offer insight into long term outcomes and further treatment needs in this unique patient population.


Introduction

In patients undergoing patent ductus arteriosus (PDA) ligation there is a significant risk of left vocal fold paralysis (LVFP) particularly in premature neonates who are small for gestational age. The objective of this study is to determine the incidence of LVFP in infants following PDA ligation and report on long-term outcomes in patients with LVFP.

Methods

We performed a prospective study of patients undergoing PDA ligation in the newborn intensive care unit (NICU) between April 2004 and May 2014. Following PDA ligation, flexible laryngoscopy was performed to assess vocal fold mobility. Patients were then followed longitudinally to determine long-term outcomes.

Results

A total of 163 infants underwent PDA ligation. Thirty-six patients (22%) developed LVFP following the procedure. Twenty-five percent of neonates <1500 g experienced LVFP versus 5% of patients >1500 g (p = 0.033). Patients with LVFP were more likely to require a feeding tube (64% vs. 19.6%; p < 0.05) and spent more time in the NICU (135 days vs. 106 days; p < 0.05). Twenty-four patients received long-term follow-up. Six (25%) had complete resolution of LVFP, 10 (42%) were compensated, and 8 (33%) demonstrated persistent LVFP with no improvement.

Conclusions

The incidence of LVFP after PDA ligation is high especially in extremely low birth weight children. The majority of patients recovered well with time, but further surgical intervention was required in uncompensated cases. Long-term follow-up of these patients is needed to ensure improvement. Laryngoscope, 2022

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Development and validation of prognostic nomograms in patients with ascending type of nasopharyngeal carcinoma: A retrospective study based on SEER database

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed.

Methods

Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted.

Results

Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677–0.711) and 0.678 (95%CI, 0.659–0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715–0.765) and 0.708 (95%CI, 0.679–0.737), separately.

Conclusion

The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

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Thursday, August 18, 2022

MicroRNA‐22 suppresses NLRP3/CASP1 inflammasome pathway‐mediated proinflammatory cytokine production by targeting the HIF‐1α and NLRP3 in Human dental pulp fibroblasts

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Aim

To investigate the synergetic regulatory effect of miR-22 on HIF-1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis.

Methodology

Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR-22-3p, NLRP3 and HIF-1α in human dental pulp tissues (HDPTs). The miR-22 mimics and inhibitor or plasmid of NLRP3 or HIF-1α were used to upregulate or downregulate miR-22 or NLRP3 or HIF-1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF-1α, NLRP3, caspase-1, IL-1β and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1β and IL-18 was analyzed by ELISA. The significance of the differences between the experimental and control groups was determined by one-way analysis of variance, P<0.05 indicated statistical significance.

Results

A decrease in miR-22 and an increase in HIF-1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p<0.05). In the normal HDPTs, miR-22-3p was extensively expressed in dental pulp cells. HIF-1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR-22-3p, HIF-1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF-1α were direct targets of miR-22 in HDPFs. The miR-22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p<0.05). In contrast, the miR-22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p<0.05).

Conclusion

MiR-22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF-1α. These results provide a novel function and mechanism of miR-22-HIF-1α-NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.

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Humoral response to heterologous prime‐booster vaccination in heart transplant recipients aged 18 to 70 years primed with a viral vector SARS‐CoV‐2 vaccine

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster).

Methods

Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay.

Results

A total of 80 heart transplant patients (mean age 49±13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28–33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p<0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p<0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine based-regimen (p = 0.007).

Conclusion

Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

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Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Development of cytomegalovirus (CMV) and BK polyoma virus (BKV) infection following kidney transplantation have been associated with allograft dysfunction and allograft loss. Reduction in immunosuppression is a mainstay of management yet has been associated with increased risk of rejection. According to international consensus guidelines, one approach to management of these viral infections is to discontinue the antimetabolite. Little is known surrounding long-term outcomes in these patients, and it remains unclear if consideration should be given to resuming the antimetabolite as variable re-escalation strategies have been reported. The objective was to describe episodes of rejection and identify risk factors for rejection following antimetabolite withdrawal after CMV or BKV DNAemia in kidney transplant recipients.

Methods

This single-center, retrospective review evaluated adult kidney transplant recipients with a serum CMV or BKV DNA PCR ≥ 500 copies/mL who underwent antimetabolite discontinuation. The primary outcome assessed was the incidence of biopsy-proven acute rejection (BPAR).

Results

159 patients were included. Overall, 14 patients (8.8%) experienced BPAR at a median of 1.6 years after antimetabolite discontinuation. Compared to CMV, discontinuation after BKV DNAemia was associated with a higher incidence of BPAR. Characteristics observed more frequently in patients with BPAR included younger age, female sex, higher initial viral load, and development of de novo donor-specific antibody (DSA).

Conclusion

These findings suggest that antimetabolite discontinuation after CMV or BKV DNAemia in kidney transplant recipients is a reasonable and safe approach. Further prospective studies investigating optimal immunosuppression management following CMV or BKV DNAemia in kidney transplant recipients are warranted.

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Wednesday, August 17, 2022

Evolution and transmission of cefiderocol-resistant Acinetobacter baumannii during an outbreak in the burn intensive care unit

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
We report 11 critically-ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and inter-patient transmission of cefiderocol-resistant A. baumannii between patients. Resistant isolates harbored disrupted pirA and piuA gen es that were not disrupted among susceptible isolates.
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