Κυριακή 21 Αυγούστου 2022

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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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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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

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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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Πέμπτη 18 Αυγούστου 2022

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

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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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Τετάρτη 17 Αυγούστου 2022

Novel mutations in antiviral multiresistant HSV‐2 genital lesion: a case report

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ABSTRACT

Introduction

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management.

Objective

To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion.

Results

Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still prese nt, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage.

Conclusions

This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

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Benign stratified intraepithelial mucinous proliferation of the uterine cervix: Significance of a previously unreported potential mimic of SMILE

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Publication date: Available online 17 August 2022

Source: Annals of Diagnostic Pathology

Author(s): Elizabeth Arslanian, Kamaljeet Singh, Katrine Hansen, M. Ruhul Quddus

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