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Kidney International Jul 2024
Topics: Humans; Kidney Transplantation; Foscarnet; Male; Immunosuppressive Agents; Middle Aged; Female; Kidney Diseases
PubMed: 38906646
DOI: 10.1016/j.kint.2024.02.017 -
Dermatology Online Journal Mar 2024The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised...
The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.
Topics: Humans; Herpes Simplex; Immunocompromised Host; Middle Aged; Female; Male; Antiviral Agents; Aged; Herpesvirus 1, Human; Adult; Valacyclovir; Herpesvirus 2, Human; Acyclovir; Valine; Immunosuppressive Agents; Foscarnet
PubMed: 38762853
DOI: 10.5070/D330163281 -
Clinical Infectious Diseases : An... Apr 2024We evaluated Ibalizumab (IBA)-containing standardized optimized salvage regimen (with or without a 4-week foscarnet induction) in individuals harboring...
We evaluated Ibalizumab (IBA)-containing standardized optimized salvage regimen (with or without a 4-week foscarnet induction) in individuals harboring multidrug-resistant human immunodeficiency virus type 2 (HIV-2). Nine were included; 2 achieved virological suppression after foscarnet induction with a sustained suppression at Week 24 after IBA initiation, and an additional individual at Week 24 after Ibalizumab initiation.
Topics: Humans; Foscarnet; HIV-2; Anti-HIV Agents; Salvage Therapy; HIV Infections; Antibodies, Monoclonal
PubMed: 38630945
DOI: 10.1093/cid/ciad695 -
Yakugaku Zasshi : Journal of the... 2024Quantitative NMR (qNMR), particularly H-qNMR, is useful for determining the absolute purity of organic molecules. However, identifying the target signal(s) for...
Quantitative NMR (qNMR), particularly H-qNMR, is useful for determining the absolute purity of organic molecules. However, identifying the target signal(s) for quantification is difficult, because of the overlap and complexity of organic molecules. Therefore, we focused on the P nucleus, owing to the simplicity of its signals, and investigated the P-qNMR absolute determination method by using organophosphorus drugs, water-soluble cyclophosphamide hydrate (CP), and water-insoluble sofosbuvir (SOF). The optimized and reproducible P-qNMR conditions, such as qNMR sample preparation [i.e., selecting suitable deuterated solvents and a reference standard (RS) for P-qNMR], hygroscopicity and solution stability of the analyte and RS, and qNMR measurements-such as acquisition time, relaxation delay time, and spectral width-were examined. The CP purities determined using P-qNMR agreed well with those for the established H-qNMR method in DO. In contrast, the SOF purity determined using P-qNMR was 1.6% higher than that for H-qNMR in the protic solvent CDOD. Therefore, using a protic solvent, such as CDOD, was not suitable for P-qNMR; the deuterium exchange with the RS for P-qNMR (i.e., phosphonoacetic acid) resulted in a small integrated intensity. Consequently, the aprotic solvent DMSO-d was employed to determine the SOF purity. The data revealed that the SOF purities determined using P-qNMR agreed well with the established H-qNMR values, indicating that the absolute quantification of SOF using both P-qNMR and H-qNMR is possible in DMSO-d. Thus, we established an optimized and reproducible P-qNMR method in validation study across multiple laboratories.
Topics: Organophosphorus Compounds; Dimethyl Sulfoxide; Water; Solvents; Pharmaceutical Preparations
PubMed: 38556308
DOI: 10.1248/yakushi.23-00151-3 -
Leukemia & Lymphoma Jun 2024Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult... (Comparative Study)
Comparative Study
Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, =0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% 26.2% ± 0.3%, = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% 64.4% ± 5.5%, = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% 58.9% ± 5.6%, = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Cytomegalovirus Infections; Valganciclovir; Male; Female; Viremia; Adult; Antiviral Agents; Foscarnet; Middle Aged; Transplantation, Homologous; Cytomegalovirus; Retrospective Studies; Young Adult; Aged; Leukemia, Myeloid, Acute; Treatment Outcome; Leukemia
PubMed: 38475670
DOI: 10.1080/10428194.2024.2321322 -
Journal of Infection in Developing... Jan 2024Human herpesvirus 6B (HHV-6B) encephalitis is common in immunosuppressed patients and presents a diagnostic challenge for physicians. Metagenomic next-generation...
Metagenomic Next-Generation Sequencing (mNGS) of cerebrospinal fluid for diagnosis of human herpesvirus 6B encephalitis following transplantation for severe aplastic anemia.
INTRODUCTION
Human herpesvirus 6B (HHV-6B) encephalitis is common in immunosuppressed patients and presents a diagnostic challenge for physicians. Metagenomic next-generation sequencing (mNGS) may facilitate early diagnosis of HHV-6B encephalitis. Herein, we described a case of HHV-6B encephalitis following transplantation for severe aplastic anemia (SAA) diagnosed by mNGS.
CASE SUMMARY
A 31-year-old male underwent myeloablative haploid hematopoietic stem cell transplantation for the treatment of SAA. On day + 21 after transplantation, the patient developed symptoms such as sudden epilepsy, drowsiness, memory dislocation, and memory loss. HHV-6B encephalitis was confirmed based on cranial MRI and mNGS of cerebrospinal fluid. Following antiviral therapy with sodium foscarnet, the symptoms improved and HHV-6B was negative by mNGS. There were no serious sequelae. Currently, the patient is in good health and is still under follow-up.
CONCLUSIONS
A case of HHV-6B encephalitis after SAA transplantation was diagnosed by mNGS of cerebrospinal fluid in time and was effectively treated with sodium foscarnet.
Topics: Male; Humans; Adult; Foscarnet; Herpesvirus 6, Human; Anemia, Aplastic; Encephalitis, Viral; Roseolovirus Infections; Hematopoietic Stem Cell Transplantation; Encephalitis; High-Throughput Nucleotide Sequencing; Sodium
PubMed: 38377081
DOI: 10.3855/jidc.18152 -
Drug Metabolism and Pharmacokinetics Apr 2024Meropenem (MEPM) is used for the treatment of serious infectious diseases solely as. INJECTABLE: Therefore, the development of an oral formulation would expand its...
Meropenem (MEPM) is used for the treatment of serious infectious diseases solely as. INJECTABLE: Therefore, the development of an oral formulation would expand its clinical utility. To this end, an exact understanding of the absorption characteristics of MEPM is essential. In this study, MEPM absorption in the rat small intestine was investigated using an in situ loop technique and an in vitro diffusion chamber method. The disappearance ratios of MEPM (0.1 mM) were in the order of ileum > duodenum > jejunum. The extensive MEPM disappearance in the ileum was significantly reduced in the presence of foscarnet, a Na-dependent phosphate transporter (NaPi-T) substrate, whereas glycylsarcosine, thiamine, taurocholic acid, and biapenem had no effects. The mucosal-to-serosal (M-to-S) permeation of MEPM across the rat ileal segments was very small under normal experimental conditions. However, on addition of 1α,25-dihydroxyvitamin D (1,25(OH)D) to the experimental medium, the M-to-S permeation of MEPM markedly increased, showing a more than 7-fold greater apparent permeation coefficient. The present results suggest that MEPM is preferentially absorbed in the rat ileum, sharing with foscarnet, and that 1,25(OH)D potentially activates the absorption of MEPM there. A likely candidate for involvement in MEPM absorption was NaPi-T or a related transporter.
Topics: Rats; Animals; Foscarnet; Meropenem; Phosphate Transport Proteins; Ileum; Intestinal Absorption; Vitamin D
PubMed: 38367298
DOI: 10.1016/j.dmpk.2024.100997 -
Transplantation Proceedings Mar 2024Cytomegalovirus (CMV) infections are common opportunistic infections in solid organ transplants (SOT) with increased health care resource USE and costs. Costs are...
BACKGROUND
Cytomegalovirus (CMV) infections are common opportunistic infections in solid organ transplants (SOT) with increased health care resource USE and costs. Costs are further increased with ganciclovir-resistance (GR). This study aimed to evaluate the real-world impact of conversion to oral step-down therapy on duration of foscarnet and hospital length of stay (LOS) for treatment of GR-CMV infections in SOT.
METHODS
This study included adult recipients of kidney or lung transplants who received foscarnet for genotypically documented GR-CMV while admitted at the University of Wisconsin Hospital from October 1, 2015, to January 31, 2022. Patients in the oral step-down group were converted from standard of care (SOC; foscarnet) to maribavir or letermovir; patients in the historical control group were treated with SOC.
RESULTS
Twenty-six patients met the inclusion criteria: 5 in the intervention group and 21 in the SOC group. The median viral load at foscarnet initiation was 11,435 IU/mL. Patients who received oral step-down conversion had shorter mean foscarnet duration than those who received SOC (7 ± 4 vs 37 ± 25 days, P = .017). Mean hospital LOS in the oral step-down group (16 ± 3 days) was shorter than the SOC group (33 ± 21 days; P < .001). In the SOC group, 9 patients lost their graft, and 9 patients died; 2 deaths were attributed to CMV. There were 2 deaths in the oral step-down group, neither of which was attributed to CMV.
CONCLUSION AND RELEVANCE
In this real-world case series of patients receiving treatment for GR-CMV infection, oral step-down conversion decreased foscarnet therapy duration and hospital LOS. Future studies are needed to evaluate better the effect of oral step-down in treating GR-CMV infection on treatment duration and cost-savings.
Topics: Adult; Humans; Cytomegalovirus; Foscarnet; Antiviral Agents; Ganciclovir; Cytomegalovirus Infections; Organ Transplantation; Transplant Recipients
PubMed: 38355369
DOI: 10.1016/j.transproceed.2024.01.052 -
The Pediatric Infectious Disease Journal May 2024Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option...
Retrospective Evaluation of Cystatin C as a Measure of Renal Function in Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Foscarnet for Cytomegalovirus Reactivation.
BACKGROUND
Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse. Our primary objective was to evaluate outcomes of patients treated with foscarnet dosed utilizing cysC-based eGFR versus SCr-based eGFR.
METHODS
We analyzed patients on the transplantation and cellular therapies service at Memorial Sloan Kettering Kids from January 2011 to September 2021 who received allogeneic hematopoietic cell transplantation and ≥14 days of foscarnet for CMV infection. Patients with cysC-based eGFR were compared to a historical cohort of patients who only had SCr-based eGFR. Outcomes included time to CMV clearance, death or change in anti-CMV therapy. Cumulative incidence curves and cause-specific hazards model were used for analysis.
RESULTS
In 61 analyzed patients, no differences were found between the cohorts in cumulative incidence of change in anti-CMV therapy ( P = 0.17) or death ( P = 0.69). After adjustment for multiple confounders, patients in the SCr cohort seemed to have a higher chance of CMV clearance compared with the cysC cohort, but the difference was not statistically significant (hazard ratio = 2.42, P = 0.089). Patients who received corticosteroids appeared to have lower incidence of CMV clearance ( P = 0.056).
CONCLUSIONS
We did not find differences in outcomes when dosing foscarnet using cysC versus SCr for treatment of CMV infection.
Topics: Humans; Child; Foscarnet; Cytomegalovirus; Cystatin C; Retrospective Studies; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Kidney; Antiviral Agents
PubMed: 38190640
DOI: 10.1097/INF.0000000000004238 -
The Journal of International Medical... Jan 2024This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC).
OBJECTIVE
This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC).
METHODS
Primary human aortic smooth muscle cells and rat aortic rings were cultured in Dulbecco's modified Eagle's medium supplemented with 0.9 mM or 2.5 mM phosphorus concentrations. Type III sodium-dependent phosphate cotransporter-1 (Pit-1) small interfering RNA and phosphonoformic acid (PFA), a Pit-1 inhibitor, were used to investigate the effects and mechanisms of Pit-1 on HPVC. Calcium content shown by Alizarin red staining, expression levels of Pit-1, and characteristic molecules for phenotypic transition of vascular smooth muscle cells were examined.
RESULTS
Hyperphosphatemia induced the upregulation of Pit-1 expression, facilitated phenotypic transition of vascular smooth muscle cells, and led to HPVC in cellular and organ models. Treatment with Pit-1 small interfering RNA or PFA significantly inhibited Pit-1 expression, suppressed phenotypic transition, and attenuated HPVC.
CONCLUSIONS
Our findings suggest that Pit-1 plays a pivotal role in the development of HPVC. The use of PFA as a Pit-1 inhibitor has the potential for therapeutic intervention in patients with HPVC. However, further rigorous clinical investigations are required to ensure the safety and efficacy of PFA before it can be considered for widespread implementation in clinical practice.
Topics: Animals; Humans; Rats; Aorta; Foscarnet; Hyperphosphatemia; RNA, Small Interfering; Transcription Factors; Vascular Calcification; Sodium-Phosphate Cotransporter Proteins, Type III
PubMed: 38180904
DOI: 10.1177/03000605231222156