Malnutrition and the Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Multi-Institutional Population-Based Propensity Score-Matched Analysis.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, exacerbating issues like malnutrition due to increased metabolic demands and reduced intake during illness. Malnutrition, a significant risk factor, is linked to worse outcomes in patients with COVID-19, such as increased mortality and extended hospital stays. This retrospective cohort study investigated the relationship between malnutrition and clinical outcomes within 90-180 days using data obtained from the TriNetX database. Patients aged >18 years diagnosed with COVID-19 between 1 January 2022, and 31 March 2024 were enrolled in the study. The propensity score-matching (PSM) method was used to match patients with malnutrition (malnutrition group) and those without malnutrition (control group). The primary composite outcome was the cumulative hazard ratio (HR) for post-COVID-19 condition, all-cause hospitalization, and all-cause mortality between 90 days and 180 days after COVID-19 diagnosis. The secondary outcomes were the individual components of the primary outcomes. Two cohorts, each consisting of 15,004 patients with balanced baseline characteristics, were identified using PSM. During the 90-180-day follow-up period, the malnutrition group exhibited a higher incidence of all-cause hospitalization, mortality, or post-COVID-19 condition (HR = 2.315, 95% confidence interval: 2.170-2.471, p < 0.0001). Compared with patients with COVID-19 without malnutrition, those with malnutrition may be associated with a higher risk of adverse clinical outcomes.

The effect of oral antiviral therapy for COVID-19 in managing non-hospitalized patients with lung cancer.

BACKGROUNDS: The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer. METHODS: Utilizing data from the TriNetX - a global health research network, a retrospective cohort study was conducted involving 2484 patients diagnosed with both lung cancer and COVID-19. Propensity score matching (PSM) was employed to create well-balanced cohorts. The study assessed the primary outcome of all-cause hospitalization or mortality within a 30-day follow-up. RESULTS: After PSM, the oral antiviral group exhibited a significantly lower risk of the primary composite outcome compared to the control group (6.1 % vs. 9.9 %; HR: 0.60; 95 % CI: 0.45-0.80). This association was consistent across various subgroups according to age, sex, vaccine status, type of oral antiviral agent, and lung cancer characteristics. Additionally, the oral antiviral group showed a lower risk of all-cause hospitalization (HR: 0.73; 95 % CI: 0.54-0.99) and a significantly lower risk of mortality (HR: 0.16; 95 % CI: 0.06-0.41). CONCLUSION: The study suggests a favorable impact of oral antiviral therapy on the outcomes of COVID-19 in individuals with lung cancer and support the potential utility of oral antiviral agents in improving outcomes in this vulnerable population.

Hypotension prediction index for prevention of intraoperative hypotension in patients undergoing general anesthesia: a randomized controlled trial.

BACKGROUND: Intraoperative hypotension is a common side effect of general anesthesia. Here we examined whether the Hypotension Prediction Index (HPI), a novel warning system, reduces the severity and duration of intraoperative hypotension during general anesthesia. METHODS: This randomized controlled trial was conducted in a tertiary referral hospital. We enrolled patients undergoing general anesthesia with invasive arterial monitoring. Patients were randomized 1:1 either to receive hemodynamic management with HPI guidance (intervention) or standard of care (control) treatment. Intraoperative hypotension treatment was initiated at HPI > 85 (intervention) or mean arterial pressure (MAP) < 65 mmHg (control). The primary outcome was hypotension severity, defined as a time-weighted average (TWA) MAP < 65 mmHg. Secondary outcomes were TWA MAP < 60 and < 55 mmHg. RESULTS: Of the 60 patients who completed the study, 30 were in the intervention group and 30 in the control group. The patients' median age was 62 years, and 48 of them were male. The median duration of surgery was 490 min. The median MAP before surgery presented no significant difference between the two groups. The intervention group showed significantly lower median TWA MAP < 65 mmHg than the control group (0.02 [0.003, 0.08] vs. 0.37 [0.20, 0.58], P < 0.001). Findings were similar for TWA MAP < 60 mmHg and < 55 mmHg. The median MAP during surgery was significantly higher in the intervention group than that in the control group (87.54 mmHg vs. 77.92 mmHg, P < 0.001). CONCLUSIONS: HPI guidance appears to be effective in preventing intraoperative hypotension during general anesthesia. Further investigation is needed to assess the impact of HPI on patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04966364); 202105065RINA; Date of registration: July 19, 2021; The recruitment date of the first patient: July 22, 2021.

Validity of the I­FEED classification in assessing postoperative gastrointestinal impairment in patients undergoing elective lumbar spinal surgery with general anesthesia: a prospective observational study.

BACKGROUND: The I-FEED classification, scored 0-8, was reported to accurately describe the clinical manifestations of gastrointestinal impairment after colorectal surgery. Therefore, it is interesting to determine whether the I-FEED scoring system is also applicable to patients undergoing lumbar spine surgery. METHODS: Adult patients undergoing elective lumbar spine surgery were enrolled, and the I-FEED score was measured for 4 days after surgery. The I-FEED scoring system incorporates five elements: intake (score: 0, 1, 3), feeling nauseated (score: 0, 1, 3), emesis (score: 0, 1, 3), results of physical exam (score: 0, 1, 3), and duration of symptoms (score: 0, 1, 2). Daily I-FEED scores were summed, and the highest overall score is used to categorize patients into one of three categories: normal (0-2 points), postoperative gastrointestinal intolerance (POGI; 3-5 points), and postoperative gastrointestinal dysfunction (POGD; 6 + points). The construct validity hypothesis testing determines whether the I-FEED category is consistent with objective clinical findings relevant to gastrointestinal impairment, namely, the longer length of hospital stay (LOS), higher inhospital medical cost, more postoperative gastrointestinal medical treatment, and more postoperative non-gastrointestinal complications. RESULTS: A total of 156 patients were enrolled, and 25.0% of patients were categorized as normal, 49.4% POGI, and 25.6% POGD. Patients with higher I-FEED scores agreed with the four validity hypotheses. Patients with POGD had a significantly longer length of hospital stay (1 day longer median stay; p = 0.049) and more inhospital medical costs (approximately 500 Taiwanese dollars; p = 0.037), and more patients with POGD required rectal laxatives (10.3% vs. 32.5% vs. 32.5%; p = 0.026). In addition, more patients with POGD had non-gastrointestinal complications (5.1% vs. 11.7% vs. 30.0%; p = 0.034). CONCLUSION: This study contributes preliminary validity evidence for the I-FEED score as a measure for postoperative gastrointestinal impairment after elective lumbar spine surgery.

Effectiveness of recently-approved oral antiviral medications on the outcome of patients with mild-to-moderate COVID-19 and pre-existing chronic obstructive pulmonary diseases.

OBJECTIVES: This study assessed the effectiveness of the oral antiviral agents nirmatrelvir - ritonavir (NMV-r) and molnupiravir (MOV) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in patients with COPD. METHODS: This retrospective cohort study extracted data from the TriNetX platform and examined 94,984 COVID-19 patients with preexisting COPD from 1 January 2022, to 1 October 2023. Patients receiving NMV-r or MOV (study group) were compared with those not receiving oral antiviral agents (control group) after propensity score matching (PSM). RESULTS: After PSM, 7,944 patients were classified into the study and control groups. The primary composite outcome of all-cause hospitalization, or death in 30 days was reported in 458 (5.7%) patients in the study group and 566 (7.1%) patients in the control cohort, yielding a hazard ratio [HR] of 0.79 (95% confidence interval [CI]: 0.70-0.89; Table 2). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (HR, 0.87; 95% CI: 0.76-0.99) and death (HR: 0.21, 95% CI: 0.13-0.35). CONCLUSIONS: This study revealed that oral antivirals - NMV-r or MOV might improve clinical outcomes in patients with preexisting COPD and COVID-19. However, only a small proportion of preexisting COPD patients with COVID-19 received oral antiviral treatment.

Ceftazidime-avibactam combination therapy versus monotherapy for treating carbapenem-resistant gram-negative infection: a systemic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to compare the efficacy of ceftazidime-avibactam combination therapy with that of monotherapy in the treatment of carbapenem-resistant Gram-negative bacterial (CR-GNB). METHODS: A literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted until September 1, 2023. Only studies that compared CZA combination therapy with monotherapy for CR-GNB infections were included. RESULTS: A total of 25 studies (23 retrospective observational studies and 2 prospective studies) involving 2676 patients were included. There was no significant difference in 30-day mortality between the study group receiving combination therapy and the control group receiving monotherapy (risk ratio [RR] 0.91; 95% confidence interval [CI] 0.71-1.18). In addition, no significant differences were observed between the study and the control group in terms of in-hospital mortality (RR 1.00; 95% CI 0.79-1.27), 14-day mortality (RR 1.54; 95% CI 0.24-9.91), 90-day mortality (RR 1.18; 95% CI 0.62-2.22), and clinical cure rate (RR 0.95; 95% CI 0.84-1.08). However, the combination group had a borderline higher microbiological eradication rate than the control group (RR 1.15; 95% CI 1.00-1.32). CONCLUSIONS: Compared to monotherapy, CZA combination therapy did not yield additional clinical benefits. However, combination therapy may be associated with favorable microbiological outcomes.

Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders.

OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

Eravacycline: a comprehensive review of in vitro activity, clinical efficacy, and real-world applications.

INTRODUCTION: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity. AREA COVERED: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety. EXPERT OPINION: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

Species selection as a key factor in the afforestation of coastal salt-affected lands: Insights from pot and field experiments.

Soil salinization is a significant global issue that leads to land degradation and loss of ecological function. In coastal areas, salinization hampers vegetation growth, and forestation efforts can accelerate the recovery of ecological functions and enhance resilience to extreme climates. However, the salinity tolerance of tree species varies due to complex biological factors, and results between lab/greenhouse and field studies are often inconsistent. Moreover, in salinized areas affected by extreme climatic and human impacts, afforestation with indigenous species may face adaptability challenges. Therefore, it is crucial to select appropriate cross-species salinity tolerance indicators that have been validated in the field to enhance the success of afforestation and reforestation efforts. This study focuses on five native coastal tree species in Taiwan, conducting afforestation experiments on salt-affected soils mixed with construction and demolition waste. It integrates short-term controlled experiments with potted seedlings and long-term field observations to establish growth performance and physiological and biochemical parameters indicative of salinity tolerance. Results showed that Heritiera littoralis Dryand. exhibited the highest salinity tolerance, accumulating significant leaf proline under increased salinity. Conversely, Melia azedarach Linn. had the lowest tolerance, evidenced by complete defoliation and reduced biomass under salt stress. Generally, the field growth performance of these species aligns with the results of short-term pot experiments. Leaf malondialdehyde content from pot experiments proved to be a reliable cross-species salinity tolerance indicator, correlating negatively with field relative height growth and survival rates. Additionally, parameters related to the photosynthetic system or water status, measured using portable devices, also moderately indicated field survival, aiding in identifying potential salt-tolerant tree species. This study underscores the pivotal role of species selection in afforestation success, demonstrating that small-scale, short-term salinity control experiments coupled with appropriate assessment tools can effectively identify species suitable for highly saline and degraded environments. This approach not only increases the success of afforestation but also conserves resources needed for field replanting and maintenance, supporting sustainable development goals.

Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

OTUB1 contributes to the stability and function of Influenza A virus NS2.

The influenza A virus (IAV) consists of 8 single-stranded, negative-sense viral RNA (vRNA) segments. After infection, vRNA is transcribed, replicated, and wrapped by viral nucleoprotein (NP) to form viral ribonucleoprotein (vRNP). The transcription, replication, and nuclear export of the viral genome are regulated by the IAV protein, NS2, which is translated from spliced mRNA transcribed from viral NS vRNA. This splicing is inefficient, explaining why NS2 is present in low abundance after IAV infection. The levels of NS2 and its subsequent accumulation are thought to influence viral RNA replication and vRNP nuclear export. Here we show that NS2 is ubiquitinated at the K64 and K88 residues by K48-linked and K63-linked polyubiquitin (polyUb) chains, leading to the degradation of NS2 by the proteasome. Additionally, we show that a host deubiquitinase, OTUB1, can remove polyUb chains conjugated to NS2, thereby stabilizing NS2. Accordingly, knock down of OTUB1 by siRNA reduces the nuclear export of vRNP, and reduces the overall production of IAV. These results collectively demonstrate that the levels of NS2 in IAV-infected cells are regulated by a ubiquitination-deubiquitination system involving OTUB1 that is necessary for optimal IAV replication.

Changing Incidence and Characteristics of Photokeratoconjunctivitis During the COVID-19 Pandemic.

Introduction: Photokeratoconjunctivitis (PKC) is primarily caused by welding. However, inappropriate use of germicidal lamps, which have been widely used following the COVID-19 outbreak, can also cause PKC. Our goal in this study was to investigate the incidence of and changes in the causes of PKC during the coronavirus 2019 (COVID-19) pandemic. Methods: We conducted a single-center, retrospective observational study. The health records of patients who visited the emergency department in a tertiary care hospital from January 1, 2018-December 31, 2021 and were diagnosed with PKC, were reviewed. We then conducted an analysis to compare the characteristics of PKC before and after COVID-19 began and the features of PKC caused by welding and germicidal lamps. Results: There were 160 PKC cases with a clear etiology before the COVID-19 pandemic and 147 cases during the COVID-19 pandemic. No significant differences in age and gender were detected between the two groups. The incidence of PKC induced by the use of germicidal lamps during the COVID-19 pandemic was significantly higher (10.2%) than the incidence before the pandemic (3.1%). The ratio of females to males in the germicidal lamp subgroup was significantly higher than the ratio in the welding subgroup. Limitations included incomplete information due to the retrospective nature of the study, underestimation of incidence, and possible recall bias. Conclusion: In the era of COVID-19, clinicians should be aware of the hazards of germicidal lamps. Although the COVID-19 pandemic seems to show signs of easing, new infectious diseases that require protective measures could still emerge in the future. Therefore, injuries related to germicidal lamps deserve more public health attention.

Nanoparticles for Augmenting Therapeutic Potential and Alleviating the Effect of Di(2-ethylhexyl) Phthalate on Gastric Cancer.

Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis of gastric cancer. This observation raised concerns regarding exposure to di(2-ethylhexyl) phthalate (DEHP), which is linked to adverse health effects, including reproductive and developmental problems, inflammatory response, and invasive adenocarcinoma. Research on the direct link between DEHP and gastric cancer is ongoing, and further studies are required to establish a conclusive association. In our study, extremely low concentrations of DEHP exerted significant effects on cell migration by promoting the epithelial-mesenchymal transition in gastric cancer cells. This effect was mediated by the modulation of the PI3K/AKT/mTOR and Smad2 signaling pathways. To address the DEHP challenges, our initial design of TPGS-conjugated fucoidan, delivered via pH-responsive nanoparticles, successfully demonstrated binding to the P-selectin protein. This achievement has not only enhanced the antigastric tumor efficacy but has also led to a significant reduction in the expression of malignant proteins associated with the condition. These findings underscore the promising clinical therapeutic potential of our approach.

Exploring the impact of culture techniques and patient demographics on the success rate of primary culture of human periodontal ligament stem cells.

Background/purpose: Periodontal ligament stem cells (PDLSCs) have the potential for regenerating periodontal tissue. The study aims to investigate the impact of demographics (ages, gender, disease) and culture techniques (shipping storage time and culture method) on the success of primary culture. Materials and methods: PDLSCs were collected from 51 teeth of 26 patients and cultured via outgrowth (OG) and enzymatic digestion (ED) methods. Cells characteristics were confirmed by flow cytometry, MTT, and ARS. The primary culture success rate was evaluated with a serial chi-square test to determine the relationship with culture technique (ED/OG and ≤4 h/prolonged culture) and patient demographics (Young/Old, Female/Male, and Health/Periodontitis). Results: The overall success rate of Health group (69.7%) was higher than Periodontitis (38.9%). Culturing within 4 h possessed a higher success rate (71.8%) than prolonged group (16.7%) regardless of patient demographics, and using OG method (81.5%) revealed more promising. Subgroup analysis of 39 cases (culture within 4 h) found that the success rate of OG was higher than ED in the Old group (87.5%-25.0%) and in the Periodontitis group (83.3%-25.0%). Conclusion: Primary culturing of PDLSCs within 4 h and using the outgrowth method led to higher success rates regardless of patient demographics. It can achieve successful PDLSCs culture of older patients or patients with periodontal disease by appropriate culture technique.

Critical distance of the sacroiliac joint for open reduction using screw fixation for traumatic sacroiliac joint diastasis: a retrospective study.

BACKGROUND: Osteosynthesis for sacroiliac joint (SIJ) diastasis using an iliosacral screw (ISS) and a trans-iliac-trans-sacral screw (TITSS) can be performed using a closed or an open method. However, no clear indication for open reduction has been established. METHODS: Data on patients with unilateral traumatic SIJ diastasis who underwent ISS and TITSS fixation were retrospectively collected and separated into groups according to the reduction method: closed reduction group (C group) and open reduction group (O group). Demographic data and perioperative image assessments were compared between the groups. The critical distance of the SIJ was identified to elucidate the indication for open reduction of the diastatic SIJ. RESULTS: Fifty-six patients met the inclusion criteria over a 3-year period. There was no significant difference in the reduction quality of pelvic ring injuries between the groups, according to Matta's and Lefaivre's criteria. The improvement in the SIJ distance was significantly greater in the O group than in the C group in the axial plane on multiplanar computed tomography (p = 0.021). This model predicted that a difference of > 3.71 mm between the injured and healthy SIJ was a recommended indication for open reduction, with an area under the curve of 0.791 (95% confidence interval 0.627-0.955, p = 0.004). CONCLUSIONS: Open reduction for SIJ diastasis might achieve better reduction quality than does closed reduction in the axial plane in selected cases. When the difference between the injured and healthy SIJ was wider than 3.71 mm, open reduction was recommended for satisfactory radiological outcomes.

Characterization of Two Highly Specific Monoclonal Antibodies Targeting the Glycan Loop of the Zika Virus Envelope Protein.

Zika virus (ZIKV) is an emerging flavivirus associated with several neurological diseases such as Guillain-Barré syndrome in adults and microcephaly in newborn children. Its distribution and mode of transmission (via Aedes aegypti and Aedes albopictus mosquitoes) collectively cause ZIKV to be a serious concern for global health. High genetic homology of flaviviruses and shared ecology is a hurdle for accurate detection. Distinguishing infections caused by different viruses based on serological recognition can be misleading as many anti-flavivirus monoclonal antibodies (mAbs) discovered to date are highly cross-reactive, especially those against the envelope (E) protein. To provide more specific research tools, we produced ZIKV E directed hybridoma cell lines and characterized two highly ZIKV-specific mAb clones (mAbs A11 and A42) against several members of the Flavivirus genus. Epitope mapping of mAb A11 revealed glycan loop specificity in Domain I of the ZIKV E protein. The development of two highly specific mAbs targeting the surface fusion protein of ZIKV presents a significant advancement in research capabilities as these can be employed as essential tools to enhance our understanding of ZIKV identification on infected cells ex vivo or in culture.