The aim of the present study was to conduct a meta-analysis for elucidating the effects of antibiotic prophylaxis on infection, rebleeding and mortality in patients who underwent endoscopic therapy for variceal hemorrhage. Articles on antibiotic prophylaxis and on-demand antibiotic administration following endoscopic therapy for acute variceal bleeding were searched on PubMed, Embase and Cochrane Library between January 1959 and February 2024, to elucidate whether the use of prophylactic antibiotics was necessary. The quality of randomized controlled trials (RCTs) was assessed using the Cochrane risk-of-bias assessment tool and RevMan software version 5.4.1 was used for meta-analysis of the data. The current meta-analysis included four RCTs and 322 patients with acute variceal bleeding who underwent endoscopic therapy. All included studies were of high quality according to the Cochrane risk-of-bias assessment tool. According to the results of the meta-analysis, the incidence of infection in the prophylactic antibiotic group was significantly lower than that in the on-demand group [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.13-0.74; P=0.009]. The prophylactic antibiotic group also exhibited a lower incidence of rebleeding compared with that of the on-demand group (OR, 0.37; 95% CI, 0.19-0.72; P=0.003). No significant differences were noted in the incidence of mortality between the two groups (OR, 0.92; 95% CI, 0.45-1.92; P=0.83). In conclusion, the data indicated that antibiotic prophylaxis is recommended to be used in patients who have undergone endoscopic therapy for variceal hemorrhage.

Patients with rheumatoid arthritis (RA) often have one or more painfuljoints despite adequate medicine. Local drug delivery to the synovial cavity bids for high drug concentration with minimal systemic adverse effects. However, anti-RA drugs show short half-lives in inflamed joints after intra-articular delivery. To improve the therapeutic efficacy, it is essential to ensure that a drug is only released from the formulation when it is needed. In this work, we developed an intelligent \"Self-actuating\" drug delivery system where Disease-modifying anti-rheumatic Drug (DMARD) methotrexate is incorporated within a matrix intended to be injected directly into joints. This formulation has the property to sense the need and release medication only when joints are inflamed in response to inflammatory enzyme Matrix metalloproteinases (MMP). These enzymes are important proteases in RA pathology, and several MMP are present in augmented levels in synovial fluid and tissues. A high level of MMP present in synovial tissues of RA patients would facilitate the release of drugs in response and ascertain controlled drug release. The formulation is designed to be stable within the joint environment, but to dis-assemble in response to inflammation. The synthesized enzyme-responsive methotrexate (Mtx) encapsulated micron-sized polymer-lipid hybrid hydrogel microspheres (Mtx-PLHM) was physiochemically characterized and tested in synovial fluid, Human Fibroblast like synoviocytes (h-FLS) (derived from RA patients) and a rat arthritic animal model. Mtx-PLHM can self-actuate and augment the release of Mtx drug upon contact with either exogenously added MMP or endogenous MMP present in the synovial fluid of patients with RA. The drug release from the prepared formulation is significantly amplified to several folds in the presence of MMP-2 and MMP-9 enzymes. In the rat arthritic model, Mtx-PLHM showed promising therapeutic results with the significant alleviation of RA symptoms through decrease in joint inflammation, swelling, bone erosion, and joint damage examined by X-ray analysis, histopathology and immune-histology. This drug delivery system would be nontoxic as it releases more drug only during the period of exacerbation of inflammation. This will simultaneously protect patients from unwanted side effects when the disease is inactive and lower the need for repeated joint injections.

The manuscript provides an overview of treatment and its changes in adult patients with haemophilia A without inhibitors in the Czech Republic between 2013 and 2021 using data from the registry of the Czech National Haemophilia Programme (CNHP). Over a 9-year period, we focused on the reduction in the annual bleeding rate (ABR), joint bleeding rate (AJBR) and factor VIII consumption when patients with severe haemophilia A switched from on-demand treatment to prophylaxis. The ABR and AJBR include both patient-reported home treatment and treated hospitalisation episodes. All adult patients with severe haemophilia A were categorised into three groups according to the therapeutic regimen. The first group was patients on prophylaxis during the follow-up period, the second group consisted of patients on on-demand treatment, and the third group was patients who received both treatment regimens during follow-up. With an increase in the proportion of patients with severe haemophilia A on prophylaxis from 37 to 74% between 2013 and 2021, the ABR for all patients with severe haemophilia A decreased approximately 6.9-fold, and the AJBR decreased 8.7-fold. Expectedly, the factor consumption increased by approximately 68.5%. In the group of patients with severe haemophilia A who had switched from an on-demand to a prophylactic regimen, the total number of bleeding events decreased 3.5-fold, and the number of joint bleeding episodes decreased 3.9-fold. Factor VIII consumption increased by 78.4%. Our study supports a previously reported positive effect of prophylaxis on bleeding control. We believe that the substantial improvement in ABR justifies the increased treatment costs.

Non-sedating H1 -antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on-demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long-term disease-modifying effects.
This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double-blind treatment, and 6 weeks of treatment-free follow-up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow-up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU-related quality of life (QoL), and disease control.
At Week 4, disease activity and QoL significantly improved in daily versus OD-treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow-up, the disease activity of patients treated OD versus daily was not significantly different.
Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule.

BACKGROUND: Prophylactic clotting factor infusion regimens to prevent bleeding and joint deformity has become the standard of care in severe hemophilia A patients.
OBJECTIVE: To assess low-dose factor prophylaxis in our population as an alternative approach to managing severe hemophilia A.
METHODS: A prospective cohort study that included 68 hemophilia A patients divided into two groups, i.e., Prophylaxis and on-demand. The two groups were compared for annualized bleeding rate (ABR), hospitalization, units of factor VIII (FVIII) infused, or plasma products transfused, i.e., fresh frozen plasma (FFP) and cryoprecipitate (CP), and development of FVIII inhibitors.
RESULTS: Of the 68 patients recruited in this study, 25 (36.7%) were in the prophylaxis group, and 43(63.3%) were in the on-demand group. The on-demand group presented a higher median-IQR ABR [8(20-3) vs. 5(10-1.5), p-value 0.024], several hospitalizations (39.7% vs. 0, p-value 0.001), and inhibitor development (9.3% vs. 0, p-value 0.289) compared to the prophylaxis group. The prophylaxis approach demonstrated a significant negative correlation of ABR with FVIII prophylaxis (r=-0484, p=value=0.014). Moreover, no hospitalizations or inhibitor development was observed in the prophylaxis group. The estimated annual consumption of FVIII was 328 IU/kg/year in the on-demand group and 1662.6 IU/kg/year in the prophylaxis group. However, a highly significant difference in plasma product utilization was observed between the two groups, i.e., p-value <0.001 and 0.038 for FFP and CP, respectively.
CONCLUSIONS: Low-dose factor prophylaxis resulted in improved outcomes compared to on-demand treatment in terms of ABR, joint bleeding, hospitalization, and the development of inhibitors. This treatment approach should be adopted as an economically feasible alternative to high-dose Prophylaxis in resource-constrained countries.

The removal to oils from water has become a global issue because of the growing of wastewater discharge and unceasing appearance of oil leaks. Herein, a kind of durably dual superlyophobic (superhydrophobic under oil and superoleophobic under water) cotton fabric (CF) was fabricated via simple assembly route that introduced guar hydroxypropyltrimonium chloride‑calcium (GHTC-Ca) chelate compound on the fabric surface. The coated CF exhibits good resistance to mechanical abrasion, corrosive aqueous solution, high temperature, and organic solvent immersion. Furthermore, due to prewetting-caused superoleophobicity underwater and superhydrophobicity underoil, the as-prepared CF can selectively separate both heavy oils and light oils in water under extremely harsh conditions with separation efficiencies as high as 98.7 % and 98.4 %, respectively. More importantly, the as-prepared fabrics are able to remove dispersed oil droplets from oil-in-water emulsions and water droplets from water-in-oil emulsions with separation efficiency of over 89 % and 91.4 %, respectively. Hence, this prominent separation performance suggests a good application prospect of GHTC-Ca functionalized CF in oily water purification.

The adoption of Enhanced Recovery After Cesarean is increasing, but evidence supporting individual interventions having a specific benefit to Enhanced Recovery After Cesarean is lacking. A key element in Enhanced Recovery After Cesarean is early oral intake. Maternal complications are more frequent in unplanned cesarean delivery. In planned cesarean delivery, immediate full feeding enhances recovery, but the effect of unplanned cesarean delivery during labor is not known.
This study aimed to evaluate immediate oral full feeding vs on-demand oral full feeding after unplanned cesarean delivery in labor on vomiting and maternal satisfaction.
A randomized controlled trial was conducted in a university hospital. The first participant was enrolled on October 20, 2021, the last participant was enrolled on January 14, 2023, and follow-up was completed on January 16, 2023. Women were assessed for full eligibility on arrival at the postnatal ward after their unplanned cesarean delivery. The primary outcomes were vomiting in the first 24 hours (noninferiority hypothesis and 5% noninferiority margin) and maternal satisfaction with their feeding regimen (superiority hypothesis). The secondary outcomes were time to first feed; food and beverage quantum consumed at first feed; nausea, vomiting, and bloating at 30 minutes after first feed, at 8, 16, and 24 hours after the operation, and at hospital discharge; parenteral antiemetic and opiate analgesia use; first breastfeeding and satisfactory breastfeeding, bowel sound, and flatus; second meal; cessation of intravenous fluid; removal of a urinary catheter; urination; ambulation; vomiting during the rest of hospital stay; and serious maternal complications. Data were analyzed using the t test, Mann-Whitney U test, chi-square test, Fisher exact test, and repeated measures analysis of variance as appropriate.
Overall, 501 participants were randomized into immediate or on-demand oral full feeding (sandwich and beverage). Vomiting in the first 24 hours were reported by 5 of 248 participants (2.0%) in the immediate feeding group and 3 of 249 participants (1.2%) in the on-demand feeding group (relative risk, 1.7; 95% confidence interval, 0.4-6.9 [0.48%-8.28%]; P=.50), and the maternal satisfaction scores from 0 to 10 were 8 (6-9) for the immediate feeding group and 8 (6-9) for the on-demand feeding groups (P=.97). The times from cesarean delivery to the first meal were 1.9 hours (1.4-2.7) vs 4.3 hours (2.8-5.6) (P<.001), first bowel sound 2.7 hours (1.5-7.5) vs 3.5 hours (1.8-8.7) (P=.02), and second meal 7.8 hours (6.0-9.6) vs 9.7 hours (7.2-13.0) (P<.001). These intervals were shorter with immediate feeding. The participants were more likely to agree to recommend immediate feeding to a friend (228 [91.9%] in the immediate feeding group vs 210 [84.3%] in the on-demand feeding group; relative risk, 1.09; 95% confidence interval, 1.02-1.16; P=.009). However, at first feed for food, ate \"nothing at all\" rates were 10.4% (26/250) in the immediate group and 3.2% (8/247) in the on-demand group, and \"eaten all\" rates were 37.5% (93/249) in the immediate group and 42.8% (106/250) in the on-demand group (P=.02). Other secondary outcomes were not different.
Compared with on-demand oral full feeding, immediate oral full feeding after unplanned cesarean delivery in labor did not increase the maternal satisfaction score and was not noninferior on postoperation vomiting. On-demand feeding with its emphasis on patient autonomy could be preferred, but the earliest full feeding should be encouraged and provided.

Temporal-spatial precision has attracted increasing attention for the clinical intervention of neurological disorders (NDs) to mitigate adverse effects of traditional treatments and achieve point-of-care medicine. Inspiring steps forward in this field have been witnessed in recent years, giving the credit to multi-discipline efforts from neurobiology, bioengineering, chemical materials, artificial intelligence, and so on, exhibiting valuable clinical translation potential. In this review, the latest progress in advanced temporally-spatially precise clinical intervention is highlighted, including localized parenchyma drug delivery, precise neuromodulation, as well as biological signal detection to trigger closed-loop control. Their clinical potential in both central and peripheral nervous systems is illustrated meticulously related to typical diseases. The challenges relative to biosafety and scaled production as well as their future perspectives are also discussed in detail. Notably, these intelligent temporally-spatially precision intervention systems could lead the frontier in the near future, demonstrating significant clinical value to support billions of patients plagued with NDs.

With an unplanned pregnancy rate of 50% or more in many countries, there is an urgent need for contraceptives that are more accessible and acceptable. To meet the growing demand for new contraceptives, ZabBio developed ZB-06, a vaginal film containing HC4-N, a human contraceptive antibody that inactivates sperm.
This study aimed to assess the potential contraceptive activity of the ZB-06 film using a surrogate assessment for contraceptive efficacy, the postcoital test. We also assessed clinical safety of film use among healthy heterosexual couples. Serum, cervical mucus, and vaginal fluid HC4-N antibody concentrations and sperm agglutination potency were determined after single film use. Changes in the concentration of soluble proinflammatory cytokines and vaginal Nugent score after film use were measured as subclinical safety endpoints.
This was a phase 1, first-in-woman, open-label, proof-of-concept, postcoital test and safety study.
A total of 20 healthy women were enrolled in the study, and 8 heterosexual couples completed all study visits. The product was safe for both female participants and their male sexual partners. The postcoital test performed on ovulatory cervical mucus at baseline (no product use) revealed a mean of 25.9 (±30.6) progressively motile sperm per high-power field. After use of a single ZB-06 film before intercourse, this number dropped to 0.04 (±0.06) progressively motile sperm per high-power field (P<.0001). At the follow-up postcoital test visit approximately 1 month later (no product use), a mean of 47.4 (±37.4) progressively motile sperm per high-power field was observed, indicating contraceptive reversibility.
A single dose of the ZB-06 film applied before intercourse was safe and met efficacy surrogate benchmarks of excluding progressively motile sperm from ovulatory cervical mucus. These data indicate that ZB-06 is a viable contraceptive candidate warranting further development and testing.

Biopharmaceuticals including protein therapeutics, engineered protein-based vaccines and monoclonal antibodies, are currently the mainstay products of the biotechnology industry. However, the need for specialized equipment and refrigeration during production and distribution poses challenges for the delivery of these technologies to the field and low-resource area. With the development of synthetic biology, multiple studies rewire the cell-free system or living cells to impact the portable, on-site and on-demand manufacturing of biomolecules. Here, we review these efforts and suggest future directions.