Antiretroviral Stewardship: Top 10 Questions Encountered by Stewardship Teams and Solutions to Optimize Therapy.

PURPOSE: Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects. Patients receiving chronic antiretroviral therapy may present to the acute care, ambulatory care, and long-term care settings. Like other antimicrobials, audit-and-feedback, drug monitoring, and dose-optimization are often required to prevent antiretroviral associated medication errors and minimize resistance. METHODS: A narrative review was conducted on antiretroviral stewardship, addressing common clinical questions encountered by stewardship teams and best practices to optimize antiretroviral therapy and reduce the risk for treatment interruptions, resistance, drug interactions, long term toxicities, and other adverse effects. FINDINGS: People living with HIV are often hospitalized and treated by medical teams without formal HIV training. For this reason, these patients are at greater risk for medication errors during hospitalization and between transitions of care. Many opportunities are present for antiretroviral stewardship to mitigate these errors. Frequent updates to simplify HIV regimen, maintain select patients on fixed-dose combination tablets, and strategies to minimize drug interactions make it difficult for even the seasoned clinician to keep up regularly. IMPLICATIONS: Despite the availability of free online HIV resources and progress made in HIV management, significant opportunities for antiretroviral stewardship remain. Implementing electronic order entry updates, formulary upgrades, and formal pharmacy renal dose adjustments to optimize antiretroviral therapy will help clinicians harness these opportunities. Dedicated time and expertise for antiretroviral stewardship as part of local antimicrobial stewardship programs are needed.

[Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia].

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

EXO1-mediated DNA repair by single-strand annealing is essential for BRCA1-deficient cells.

Deficiency for the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) leads to chromosomal instability and diseases such as cancer. Yet, defective HR also results in vulnerabilities that can be exploited for targeted therapy. Here, we identify such a vulnerability and show that BRCA1-deficient cells are dependent on the long-range end-resection factor EXO1 for survival. EXO1 loss results in DNA replication-induced lesions decorated by poly(ADP-ribose)-chains. In cells that lack both BRCA1 and EXO1, this is accompanied by unresolved DSBs due to impaired single-strand annealing (SSA), a DSB repair process that requires the activity of both proteins. In contrast, BRCA2-deficient cells have increased SSA, also in the absence of EXO1, and hence are not dependent on EXO1 for survival. In agreement with our mechanistic data, BRCA1-mutated tumours have elevated EXO1 expression and contain more genomic signatures of SSA compared to BRCA1-proficient tumours. Collectively, our data indicate that EXO1 is a promising novel target for treatment of BRCA1-deficient tumours.

Antimicrobial Stewardship and Pandemic Preparedness: Harnessing Lessons Learned to Advance Our Mission.

Antimicrobial stewardship programs (ASPs) demonstrated poise and resilience in assisting with COVID-19 efforts across the globe, harnessing expertise in diagnostic stewardship, therapeutics, protocol development, and use of technology to rapidly expand their scope through strategic collaborations, dissemination of content expertise, and numerous contributions to the body of knowledge on COVID-19. Lessons learned from pandemic response should be used to advance the mission of ASPs and secure a "seat at the table" as health systems continue to expand and adapt to future public health crises.

[Long term follow-up evaluation of combined surgery for congenital tibial pseudarthrosis in children].

Objective: To explore the long-term effect of combined surgery for the treatment of congenital tibial pseudarthrosis in children. Methods: The clinical data of 44 children with congenital tibial pseudarthrosis who underwent combined surgery (tibial pseudarthrosis tissue resection, intramedullary rod fixation, Ilizarov external fixator fixation, wrapped autologous iliac bone graft) from August 2007 to October 2011 at the Department of Pediatric Orthopedics, Hunan Children's Hospital were collected retrospectively. There were 33 males and 11 females. The age at the time of surgery was (3.7±2.2)years (range:0.6 to 12.4 years), including 25 cases under 3 years old and 19 cases above 3 years old.Among them, 37 cases were complicated with neurofibromatosis type 1.The operation status, postoperative complications and follow-up results were recorded. Results: The follow-up time after surgery was (10.9±0.7)years (range:10 to 11 years).Thirty-nine out of 44 patients (88.6%) achieved initial healing of tibial pseudarthrosis, with an average healing time of (4.3±1.1)months (range:3 to 10months).In the last follow-up, 36 cases (81.8%) had unequal tibial length, 20 cases (45.4%) had refractures, 18 cases (40.9%) had ankle valgus, 9 cases (20.4%) had proximal tibial valgus, and 11 cases (25.0%) had high arched feet.Nine cases (20.4%) developed distal tibial epiphyseal plate bridging.17 cases (38.6%) had abnormal tibial mechanical axis.Seven cases (15.9%) developed needle infection, and one case (2.3%) developed tibial osteomyelitis. 21 patients (47.7%) had excessive growth of the affected femur.Five patients (11.3%) had ankle stiffness, and 34 patients (77.2%) had intramedullary rod displacement that was not in the center of the tibial medullary cavity.Among them, 8 cases (18.1%) protruded the tibial bone cortex and underwent intramedullary rod removal.18 children have reached skeletal maturity, while 26 children have not been followed up until skeletal maturity. Conclusion: Combined surgery for the treatment of congenital pseudarthrosis of the tibia in children has a high initial healing rate, but complications such as unequal tibia length, refracture, and ankle valgus occur during long-term follow-up, requiring multiple surgical treatments.

Validation of an LC-MS/MS method for simultaneous quantification of abiraterone, enzalutamide and darolutamide in human plasma.

Currently, several oral androgen receptor signalling inhibitors are available for the treatment of advanced prostate cancer. Quantification of plasma concentrations of these drugs is highly relevant for various purposes, such as Therapeutic Drug Monitoring (TDM) in oncology. Here, we report a liquid chromatography/tandem mass spectrometric (LC-MS/MS) method for the simultaneous quantification of abiraterone, enzalutamide, and darolutamide. The validation was performed according to the requirements of the U.S. Food and Drug Administration and European Medicine Agency. We also demonstrate the clinical applicability of the quantification of enzalutamide and darolutamide in patients with metastatic castration-resistant prostate cancer.

Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients.

OBJECTIVES: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. METHODS: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. RESULTS: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4-3.3, P value = 0.79). CONCLUSIONS: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

Metasurface-enhanced mid-infrared spectrochemical imaging of tissues.

Label-free and nondestructive mid-infrared vibrational hyperspectral imaging is emerging as an important ex-vivo tissue analysis tool, providing spatially resolved biochemical information critical to understanding physiological and pathological processes. However, the chemically complex and spatially heterogeneous composition of tissue specimens and the inherently weak interaction of infrared light with biomolecules limit the analytical performance of infrared absorption spectroscopy. Here, we introduce an advanced mid-infrared spectrochemical tissue imaging modality using metasurfaces that support strong surface-localized electromagnetic fields to capture quantitative molecular maps of large-area murine brain-tissue sections. Our approach leverages polarization-multiplexed multi-resonance plasmonic metasurfaces to simultaneously detect many different functional biomolecules. The resulting surface-enhanced mid-infrared spectral imaging (SE-MIRSI) method eliminates the non-specific effects of bulk tissue morphology on the quantitative analysis of fingerprint spectra and improves the chemical selectivity. We show that the metasurface enhancement increases the retrieval of amide I and II absorption bands associated with secondary structures of proteins. Moreover, we demonstrate that plasmonic metasurfaces enhance the chemical contrast in infrared images and enable the detection of ultrathin tissue regions that are not otherwise visible to conventional mid-infrared spectral imaging. While we tested our approach on murine brain tissue sections, this chemical imaging method is well-suited for any tissue type, which significantly broadens the potential impacts of our method for both translational research and clinical histopathology.

Expanding the scope and visibility of ambulatory stewardship programs with novel coronavirus disease 2019 (COVID-19) therapeutics.

Antimicrobial stewardship programs (ASPs) can be expanded to the outpatient setting to serve as a first line of defense against coronavirus disease 19 (COVID-19) hospitalizations and to reduce the burden on emergency departments and acute-care hospitals. Given the numerous emergency use authorizations of monoclonal antibodies and oral antivirals, ASPs possess the expertise and leadership to direct ambulatory COVID-19 initiatives and transform it into a predominantly outpatient illness. In this review, we summarize the critical role and benefits of an ASP-championed ambulatory COVID-19 therapeutics program.

Effect of Hypoxic-Ischemic Brain Injury in Neonatal Rats on Behavioral Parameters and Expression of CDK8 in the Brain Tissue.

Behavioral changes in newborn 3-day-old rats (n=44) with modeled hypoxic-ischemic brain injury (HIBI) were observed, and the expression of CDK8 in brain tissues was detected to clarify the significance of CDK8. In 30 min, 3 h, and 3 days after HIBI, the left (ischemic) hemisphere was taken for examination. In 3 days after HIBI, the rat pups were examined in the behavioral tests. In rat pups with HIBI, changes of CDK8 expression were detected by Western blotting and real-time PCR and changes in the righting reflex and forelimb grip strength test (p<0.05) were revealed in comparison with sham-operated animals. The expression of CDK8 increased 30 min after HIBI and decreased in 3 h and 3 days. Hypoxia and ischemia of the left brain may affect locomotion, but not sensation. Since CDK8 is involved in the immune response after cerebral hypoxia and ischemia, this kinase can be used as an early diagnostic index.

[Phenotypes and ATP7B gene variants in 316 children with Wilson disease].

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 µg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) µg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China. OBJECTIVES: The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China. METHODS: Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates. RESULTS: Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non-recurrent VVC. CONCLUSIONS: Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

Inheritance of physico-chemical properties and ROS generation by carbon quantum dots derived from pyrolytically carbonized bacterial sources.

Bacteria are frequently used in industrial processes and nutrient supplementation to restore a healthy human microflora, but use of live bacteria is often troublesome. Here, we hypothesize that bacterially-derived carbon-quantum-dots obtained through pyrolytic carbonization inherit physico-chemical properties from probiotic and pathogenic source-bacteria. Carbon-quantum-dots carbonized at reaction-temperatures below 200 â€‹°C had negligible quantum-yields, while temperatures above 220 â€‹°C yielded poor water-suspendability. Fourier-transform infrared-spectroscopy demonstrated preservation of amide absorption bands in carbon-quantum-dots derived at intermediate temperatures. X-ray photoelectron-spectroscopy indicated that the at%N in carbon-quantum-dots increased with increasing amounts of protein in source-bacterial surfaces. Carbonization transformed hydrocarbon-like bacterial surface compounds into heterocyclic aromatic-carbon structures, evidenced by a broad infrared absorption band (920-900 â€‹cm-1) and the presence of carbon in C-C functionalities of carbon-quantum-dots. The chemical composition of bacterially-derived carbon-quantum-dots could be explained by the degradation temperatures of main bacterial cell surface compounds. All carbon-quantum-dots generated reactive-oxygen-species, most notably those derived from probiotic lactobacilli, carrying a high amount of surface protein. Concluding, amide functionalities in carbon-quantum-dots are inherited from surface proteins of source-bacteria, controlling reactive-oxygen-species generation. This paves the way for applications of bacterially-derived carbon-quantum-dots in which reactive-oxygen-species generation is essential, instead of hard-to-use live bacteria, such as in food supplementation or probiotic-assisted antibiotic therapy.

[Infectious complications following chimeric antigen receptor T-cell therapy for a hematologic malignancy within 28 days].

Objective: To explore the incidence, clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic (ALL) , non-Hodgkin lymphoma (NHL) , and multiple myeloma (MM) within 28 days after CAR-T cell infusion. It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients. Methods: We retrospectively analyzed the baseline data of 170 patients with ALL, NHL and MM who received chimeric antigen receptor-modified T (CAR-T) -cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020, and the clinical characteristics of infection within 28 days after infusion, including 72 patients with ALL, 56 patients with NHL, and 42 patients with MM; we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion, respectively. Results: Among 170 patients, 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The infection density was 2.01, and the median time for the first infection was about 12 days after infusion. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, absolute neutrophil count (ANC) <0.5×10(9)/L before infusion and ≥4 prior antitumor treatment regimens had a higher infection density within 28 days; grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusion: Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10(9)/L before infusion and grade 3 or 4 CRS are risk factors for infection. Chinese Clinical Trial Register:: ChiCTR-OIC-17011180, ChiCTR1800018143.

Editorial - Infectious-disease research during a pandemic: the importance of global unity.

The orthopaedic and trauma community have faced the threat of infection since the introduction of operative fracture fixation many decades ago. The parallel emergence and spread of antimicrobial resistance in clinically relevant pathogens has the potential to significantly complicate patient care. This editorial serves to provide a global context to the issue of antimicrobial resistance and how infectious disease research in general plays a crucial role both on a global scale as evidenced by the current pandemic, but also on a more personal scale for the daily management of orthopaedic trauma patients. The special issue on Orthopaedic Infection in the eCM journal provides a snapshot of the clinically relevant basic research that is being performed in this field.

[Genetic etiology of newborn deaths].

Objective: To explore the genetic etiologies of newborn deaths. Methods: A total of 98 newborns who were recruited to the Neonatal Genome Project of the Children's Hospital of Fudan University and died in the hospital from January 2018 to August 2020 were enrolled in this study. The genetic information and the interventions based on the genetic findings were retrospectively analyzed. T-test, Mann-Whitney U test, Chi square test and Fisher's exact probability test were used to compare the demographic features and clinical characteristics between the patients with or without a genetic finding. Results: Among 98 newborns (55 males and 43 females), there were 63 preterm and 35 term infants, with a gestational age of (33±5) weeks, a birth weight of (2 107±975) g and the age at death of 12 (2,34) days. Sixteen (16%)patients were identified with genetic variants, including 11 with single nucleotide variants, 4 with copy number variants and 1 with both single nucleotide variant and copy number variant. The detected single nucleotide variants were spanning 12 genes, among which 3 were multiple disorders-related, 2 metabolic disorder-related, 2 hematological disorder-related, 2 respiratory disorder-related, 2 cardiovascular disorder-related and 1 skeletal disorder-related. The patients with a positive genetic finding had significant differences in the birth weight ((2 605±940) vs. (2 009±957) g, t=2.283, P=0.025), the gestational age ((36±5) vs. (33±5) weeks, t=2.131, P=0.036), the age at death ((37 (5, 69) vs. 11 (2, 29) days, Ζ=-2.245, P=0.025) and the history of asphyxia at birth (1/16 vs. 46% (38/82), P=0.002)when compared to those without a genetic finding. In addition, the genetic etiology rates of patients who were born term or with a birth weight ≥ 2 000 g were significantly higher than those who were born preterm (29% (10/35) vs. 10% (6/63), P=0.022) or with a birth weight<2 000 g (25% (13/51) vs. 7% (3/46), χ2=5.016,P=0.025), respectively. Six cases were medically actionable based on the genetic findings and the treatments included special diet, applying specific medicine, hematopoietic stem cell transplantation and lung transplantation. Conclusions: Genetic etiologies are not rare in newborn deaths and mainly associated with metabolic disorder, multi-system disorders, hematological disorder, respiratory disorder, cardiovascular disorder and skeletal disorder. Some findings are medically actionable, based on which the specific treatments could be scheduled timely. A genetic etiology should be investigated in newborn deaths especially in those who are term birth or with a birth weight ≥2 000 g or without a history of asphyxia at birth.