Observation Time Points Research Articles

Bilateral Rectus Sheath Block with Continuous Bupivacaine Infusions After Elective Open Gastrectomy: A Randomized Controlled Trial

Background and Objectives: Multimodal analgesia has been shown to be effective in facilitating early postoperative gastrointestinal function and rehabilitation in patients undergoing open gastrectomy. We conducted a clinical trial to investigate the effectiveness of bilateral rectus sheath block (RSB) with continuous bupivacaine infusion in comparison with placebo following elective open gastrectomy. Materials and Methods: Patients indicated for elective open gastrectomy were screened, enrolled, and randomised between October 2021 and September 2023. The patients were randomised to either Group A (intervention—continuous bupivacaine) or Group B (control—NaCl saline). The primary outcome measures were the quantity of an opioid analgesic administered during the initial 72 h post-surgery and the level of postoperative pain as indicated by the visual analogue scale (VAS). Mann–Whitney U test was used for quantitative analysis while Pearson Chi-square was used for categorical variables. Results: A total of 60 patients completed the trial, with 30 patients in each of the two groups. Patients in Group A reported lower median VAS pain scores at all observed time points following surgery (p < 0.001). No patient in Group A required rescue opioid analgesia, although non-steroidal anti-inflammatory drugs were necessary during the initial 12 h postoperatively. Clinically, Group A patients had a significantly shorter time to first gas (p = 0.001), a shorter time to first bowel movement (p < 0.001), a shorter time to first out-of-bed activity (p < 0.001), and a shorter overall hospitalisation duration (p < 0.001) compared to Group B patients. Conclusions: Bilateral RSB with continuous bupivacaine infusion is effective in managing pain and can reduce the use of opioid analgesics in the postoperative period. Furthermore, it promotes early recovery, and a shorter hospital stay.

Safety and Efficacy of Photodynamic Therapy with ALA 10% Topical Gel Activated by Red Light versus ALA 20% Topical Solution Activated by Blue Light for the Treatment of Actinic Keratosis on the Upper Extremities: A Blinded Randomized Study

Background: Actinic keratosis (AKs) is a pre-cancerous skin neoplasm that can appear as erythematous to pink scaly plaques at sites of ultraviolet light damage. Photodynamic therapy (PDT) using aminolaevulinic acid (ALA) 10% gel activated by red light is approved by the FDA for the treatment of AKs on the face and scalp, and ALA 20% solution activated by blue light is approved for PDT treatment of AKs on the face, scalp, and upper extremities. While both options have been proven to an effective treatment on the upper extremity, there has been no direct side-by-side comparison. This study aimed to compare the safety and efficacy of both PDT on the upper extremities. Design: This was a prospective, single-center, split-arm randomized clinical trial with 20 adult subjects presenting with 4-17 clinically confirmed mild-moderate AKs (Olsen grading) on each distal upper extremity. Subjects were treated with ALA 10% gel/red light and ALA 20% solution/blue light PDT on respective randomly selected upper extremities. Lesion complete clearance rate (LCCR) served as the primary endpoint. Secondary endpoints included complete clearance per patient side (PatCR), LCCR of moderate lesions, LCCR 12 weeks after PDT-1, PatCR 12 weeks after PDT-1, overall cosmetic outcome assessed by the investigator, and patient satisfaction. Results: The LCCR was significantly greater for ALA10% vs. ALA20% at Day 120; no significant differences were observed at the other observed time points. 30 patients were enrolled in the study and received their first treatment (PDT1). LCCRs after PDT1 were 65.4% and 58.4% for ALA10% and ALA 20%, respectively. 25 patients received a second treatment (PDT2), resulting in LCCRs of 88.2% and 72.1% respectively. 22 patients returned for follow-up 6 months after their last PDT treatment (PDT1 or PDT2), with LCCR of 83.7% (ALA10%) and 79.3% (ALA20%). 17 patients returned for follow-up 12 months after the last PDT treatment, with LCCRs of 81.5% (ALA10%) and 87.6% (ALA20%). There were no statistical differences between ALA10% and ALA20% for subject-reported pain or satisfaction ratings. ALA10% was rated as significantly easier to apply compared to ALA20% by the investigator. Conclusion: Both ALA10% and ALA20% appear to be safe and effective for PDT treatment of AKs on the upper extremities. There is a trend for increased efficacy with ALA10%, and it may be easier to apply. Additional data is in the process of being collected as the study continues.

Randomized, multicenter, active-controlled open-label study of NPC-25, zinc histidine hydrate, (non-inferiority to NOBELZINTM, zinc acetate dihydrate) for patients with hypozincemia

ObjectiveThis study evaluated the efficacy and safety of NPC-25, zinc histidine hydrate, in patients with hypozincemia. This randomized multicenter active-controlled open-label trial aimed to verify the non-inferiority of NPC-25 to NOBELZINTM, zinc acetate dihydrate. MethodsParticipants whose serum zinc concentrations were <70 μg/dL at two points within 8 weeks before the start of treatment were randomized 1:1 into the NPC-25 (active drug) administration group and the NOBELZINTM (control drug) administration group, using dynamic allocation. The initial daily doses were 50mg or 100mg as the baseline serum zinc levels, and administration periods were set at maximum of 24 weeks with the goal of maintaining the target serum zinc concentration (≥80 and <200 μg/dL) for 8 weeks, with extension up to 52 weeks as needed in the NPC-25 group, but not the NOBELZIN group. The primary efficacy endpoint was the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dosage within 24 weeks after the start of administration. The key secondary endpoints were the cumulative achievement percentage for target serum zinc concentration at each observation time point, the cumulative achievement percentage for maintenance of target concentration for 8 weeks at the same dosage at each observation time point, change in mean serum zinc concentration, and comparison of dosage amount. Safety assessments included the incidence of adverse events and adverse drug reactions, as well as changes in clinical laboratory and physical measurements. ResultsFor the primary endpoint for full analysis (FAS) set (n=103, NPC-25 group; n=107, NOBELZIN group), the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dose was 86.4% (89/103) in the NPC-25 group and 80.4% (86/107) in the NOBELZIN group, which confirmed the non-inferiority of NPC-25 to NOBELZINTM. For the secondary endpoint for FAS, at each observation point, although there was no significant difference between the two groups in the proportion of participants who achieved the target serum zinc concentration, there was a tendency that the maintenance of the target concentration for 8 weeks was achieved earlier with NPC-25.There was also a tendency to achieve maintenance with a lower daily dose in the NPC-25 group. Furthermore, at each observation point, there was no significant difference between the two groups in terms of the mean serum zinc concentration or the average change in serum zinc concentration from baseline. In the safety assessment for safety population (SP), the incidence of nausea and vomiting was lower with NPC-25 than with NOBELZIN (2.8% and 6.4% with nausea, 0.9% and 2.8% with vomiting), but there were no significant differences in other adverse drug reactions. ConclusionIn this study, non-inferiority of NPC-25 to NOBELZINTM was confirmed in terms of efficacy and safety. Furthermore, regarding safety, NPC-25 resulted in a lower frequency of digestive symptoms, such as nausea and vomiting.

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series

CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis. Six patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 106 CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months. Between April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint. We provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis. Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.

Evaluation of the chronic oral toxicity of the classical ancient prescription Kai-Xin-San

Ethnopharmacological relevanceThe Kai-Xin-San (KXS), as an ancient classic prescription, has been used for the treatment of amnesia for thousands of years. Modern clinical and non-clinical pharmacological studies have found that it has significant therapeutic effects on dementia and depression, but there are relatively few studies on its safety. Aim of the studySubacute and chronic toxicity studies were conducted to investigate the symptoms, severity, target organs, development and recovery of toxic reactions, as well as the toxic dose. These studies provide technical data for ensuring the safety of KXS. Materials and methodsIn the sub-acute toxicity study, rats were orally administered KXS at doses of 0.80, 1.61, 3.22, and 6.43 g/kg body weight for a duration of 4 weeks. In the chronic toxicity study, rats were orally administered KXS at doses of 0.27, 0.81, and 2.43 g/kg body weight for a duration of 26 weeks, and a withdrawal study was conducted for a period of 4 weeks after the treatment.The rats were observed daily for clinical signs and mortality. Changes in body weight, food consumption, and water consumption were periodically monitored. Additionally, urinalysis results, hematological and biochemical parameters, relative organ weights, and pathology were monitored at specific observation time points. ResultsIn the sub-acute toxicity study, necropsy of dead and moribund rats revealed evident distension and swelling of the gastrointestinal tract, as well as thinning of the intestinal wall. The main adverse reactions observed included flatulence, piloerection, abnormal breathing sounds, and emaciation. Doses of 1.61 g/kg and below did not cause animal death. The gastrointestinal system is the main target organ of toxicity. In the chronic toxicity study, the no-observed-adverse-effect-level (NOAEL) of KXS was 0.27 g/kg, and its toxic effects were primarily concentrated in the gastrointestinal system. This led to secondary pathological changes in the immune system, hematopoietic system, and heart, suggesting that relevant indicators should be monitored when large doses are used clinically for an extended period of time. ConclusionsDuring the rodent toxicity evaluation, severe gastrointestinal damage was observed when KXS, powdered with crude drugs, was administered. The NOAEL for rats was found to be 0.27 g/kg/day.

Rate and risk factors of tip displacement of umbilical venous catheterization at different indwelling time points in preterm infants

Objectives: To investigate the rate and risk factors of tip displacement of umbilical venous catheterization (UVC) in preterm infants. Methods: This was a multicenter cohort study. Study population were preterm infants admitted to 44 tertiary hospitals in China between October 2019 and August 2021. Demographic information, general clinical data, UVC indwelling conditions and related complications were collected. The primary outcome was the rate of UVC tip displacement. The observation time points were 2 d and 7 d after UVC. They were grouped according to UVC displacement, gestational age, and birth weight. Binary Logistic regression was used to analyze the risk factors of UVC tip displacement. Results: The 2 086 preterm infants had a gestational age of (29.9±2.3) weeks and a birth weight of (1 248±298) g. There were 1 106 male preterm infants (53.0%). The rate of UVC displacement at 2 d and 7 d were 34.6% (721/2 086) and 33.6% (494/1 470), respectively, with no statistically significant difference (χ2=0.35, P=0.533). Univariate analysis indicated that male infants, small gestational age, low birth weight and small catheter diameter were all risk factors for UVC tip displacement at the 2 d time point (all P<0.05). Multivariate analysis showed that small catheter diameter was an independent risk factor for tip displacement at both 2 d (OR=0.47, 95%CI 0.34-0.66) and 7 d (OR=0.39, 95%CI 0.25-0.59) time points (both P<0.001). Conclusions: The rate of UVC tip displacement is high in preterm infants. It should be avoided to deliberately select a small diameter catheter for UVC, and pay attention to the imaging monitoring of the tip position after UVC.

Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: a Randomized, double-blind controlled trial

Study objectiveAdvanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer.DesignRandomized, Double-Blind Controlled Trial.SettingSichuan Cancer Hospital & Institute and Yanjiang District People’s Hospital in Sichuan, China.ParticipantsA total of 72 patients with advanced rectal cancer experiencing perineal pain who were accepted for radiofrequency treatment.InterventionsPatients were assigned randomly (1:1) assigned to either the group CRF or H-PRF in a double-blind trial.Measurements and main resultsThe primary focus was on assessing perineal pain using numeric rating scales (NRS) scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness. A total of 57 patients (28 patients in the group CRF and 29 patients in the group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements (P<0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF (P<0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups (P > 0.05).ConclusionOur results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF.Trial registrationhttps://www.chictr.org.cn/ (ChiCTR2200061800) on 02/07/2022. This study adheres to CONSORT guidelines.

Deep Molecular Response Rate in Chronic Phase Chronic Myeloid Leukemia: Eligibility to Discontinuation Related to Time to Response and Different Frontline TKI in the Experience of the Gimema Labnet CML National Network

BackgroundIn the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients. MethodsData were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring. ResultsOut of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with <MR2, with dasatinib 66% versus 28% of patients with <MR2, and with nilotinib 75% versus 30% of patients with < MR2 (P < .001). At the same time point, achieving at least ≥MR3 is even more predictive of a DMR at any timepoint: 89% versus 38% of patients with <MR3 with imatinib (P < .001), 84% versus 40% of patients with <MR3 with dasatinib (P < .001), and 89% versus 49% of patients with <MR3 with nilotinib (P < .001). Of 908 patients who reached a DMR, 461 (51%) lost it: the loss of response after >2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with <MR2, P = .038). ConclusionIn conclusion, reaching ≥MR2 and a MR3 at 3 months it seems predictive of a DMR at any time point. Considering the prerequisite for a discontinuation with a sustained DMR only a minority of patients can be eligible for the discontinuation, regardless the frontline treatment received.

Learning metabolic dynamics from irregular observations by Bidirectional Time-Series State Transfer Network.

Modeling microbial metabolic dynamics is important for the rational optimization of both biosynthetic systems and industrial processes to facilitate green and efficient biomanufacturing. Classical approaches utilize explicit equation systems to represent metabolic networks, enabling the quantification of pathway fluxes to identify metabolic bottlenecks. However, these white-box models, despite their diverse applications, have limitations in simulating metabolic dynamics and are intrinsically inaccurate for industrial strains that lack information on network structures and kinetic parameters. On the other hand, black-box models do not rely on prior mechanistic knowledge of strains but are built upon observed time-series trajectories of biosynthetic systems in action. In practice, these observations are typically irregular, with discontinuously observed time points across multiple independent batches, each time point potentially containing missing measurements. Learning from such irregular data remains challenging for existing approaches. To address this issue, we present the Bidirectional Time-Series State Transfer Network (BTSTN) for modeling metabolic dynamics directly from irregular observations. Using evaluation data sets derived from both ideal dynamic systems and a real-world fermentation process, we demonstrate that BTSTN accurately reconstructs dynamic behaviors and predicts future trajectories. This approach exhibits enhanced robustness against missing measurements and noise, as compared to the state-of-the-art methods.IMPORTANCEIndustrial biosynthetic systems often involve strains with unclear genetic backgrounds, posing challenges in modeling their distinct metabolic dynamics. In such scenarios, white-box models, which commonly rely on inferred networks, are thereby of limited applicability and accuracy. In contrast, black-box models, such as statistical models and neural networks, are directly fitted or learned from observed time-series trajectories of biosynthetic systems in action. These methods typically assume regular observations without missing time points or measurements. If the observations are irregular, a pre-processing step becomes necessary to obtain a fully filled data set for subsequent model training, which, at the same time, inevitably introduces errors into the resulting models. BTSTN is a novel approach that natively learns from irregular observations. This distinctive feature makes it a unique addition to the current arsenal of technologies modeling metabolic dynamics.

Clinical features and prognostic factors of cryptococcal infections in HIV-infected patients: a 10-year study from an infectious disease specialist hospital.

Cryptococcosis is an invasive infection that commonly affects immunosuppressed individuals, especially patients with HIV infection. Cryptococcal infection in HIV-infected patients should be considered a major health concern because it is associated with high morbidity and mortality rates. In this study, we aimed to evaluate the clinical characteristics and prognostic factors of cryptococcal infections in human immunodeficiency virus (HIV)-infected patients to facilitate effective clinical management and improve patient outcomes. We reviewed and analyzed the clinical data and relevant laboratory test results of HIV-infected patients with positive cryptococcal cultures and reserved strains between 2013 and 2023 from Beijing Youan Hospital affiliated to Capital Medical University. The clinical characteristics and laboratory test results of the patients were compared, and the correlation between parameters and the prognoses of the patients at different observation timepoints (3, 6, 9, and 12 months) was analyzed. A total of 76 patients (70 males and six females; median age, 37 years) were included in this study. The results indicated that the later the initiation of antiretroviral therapy (ART) after the diagnosis of HIV infection (> 6 months), the higher the probability of death. Analysis of the correlation between the time of ART initiation and the timing of treatment for cryptococcal infections showed that the time of ART initiation was strongly related to survival at different timepoints. Initiation of ART time within 0-4 weeks, 4-6 weeks and more than 6weeks of starting treatment for Cryptococcus infection was associated with a lower mortality rate at 12-month, the 3-month, 6- and 9-month follow-up timepoint separately. Although cryptococcal infection in HIV-infected patients continues to be a challenging and intricate issue, ART is a key factor that affects its prognosis. The later ART is started, the worse the prognosis of the infection. The time of ART initiation and the timing of treatment for cryptococcal infections should be further refined and balanced based on different clinical courses. Thus, clinicians should pay closer attention to cryptococcal infections in patients with HIV infection and initiate ART based on the patient's clinical condition.

Comparison of analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block with liposomal bupivacaine after arthroscopic rotator cuff repair

Objective: To compare the postoperative analgesic effect of modified superior trunk block and traditional interscalene brachial plexus block in arthroscopic rotator cuff repair. Methods: A total of 40 patients undergoing arthroscopic rotator cuff repair in the Second Affiliated Hospital of Wenzhou Medical University from October to November 2023 were prospectively included, whose American Society of Anesthesiologists (ASA) grade were Ⅰ-Ⅱ. They were divided into modified superior trunk block group (group S) and interscalene brachial plexus block group (group I) by random number table according to different nerve block methods, with 20 cases in each group. Local anesthetics was a mixture of 1.33% liposomal bupivacaine and 0.5% levobupivacaine hydrochloride injection in equal volume. Patients in group S were injected 5 ml mixture for ultrasound-guided modified superior trunk block, and patients in group I were injected with 15 ml mixture for ultrasound-guided traditional interscalene block respectively. Both groups underwent superficial cervical plexus block (5 ml mixture). Standardized general anesthesia and standardized postoperative analgesia were followed. The primary outcome measures included 48 h resting numerical rating scale (NRS) scores after surgery and the incidence of hemidiaphragmatic paralysis (HDP) at 30 min after block. The secondary outcome measures included resting NRS scores during the post anesthesia care unit (PACU), 12, 24, and 36 h after surgery, postoperative opioid consumption and satisfaction with analgesia, pulse oxygen saturation (SpO2) at 30 min after block, sensory and motor block duration, and the incidence of perioperative adverse reactions. The non-inferiority cut-off value of resting NRS scores for patients in group S was set as"1 point"at each observation time point after surgery. Results: In group S, one patient was excluded because the target nerve was blocked by the subclavian vein and could not be blocked, nineteen patients [11 males and 8 females, aged (52.2±9.0) years] were eventually included. In group I, there were 7 males and 13 females, aged (55.0±5.1) years. Resting NRS scores of group S and Group I at 48 h after surgery were 0 (0, 0) and 0 (0, 0.8) point, respectively, with no statistical significance (P>0.05). The median difference was 0 (95%CI:0-0) point and the upper 95%CI was 0 point, which was lower than the preset non-inferiority cut-off value"1 point"(non-inferiority P<0.001). The incidence of HDP in group S and group I were 5% (1/19) and 75% (15/20), respectively, with statistically significant (P<0.001). There were no significant differences in resting NRS scores at PACU and 12, 24, 36 h after surgery, opioid dosage, satisfaction with analgesia, SpO2 at 30 min after block, sensory and motor block duration between two groups (all P>0.05). No respiratory adverse events such as hypoxemia and airway spasm occurred in two groups after extubation. One patient in group I showed symptoms of breath shortness when entering PACU, and 3 patients felt uncomfortable due to prolonged numbness and weakness of the blockade limb (>2 days). No nerve block procedures and opioid drugs relative adverse reactions and no neurological complications happened in both groups. Conclusion: Liposomal bupivacaine usage for modified superior trunk block can provide long-term postoperative analgesic effects which is noninferior to traditional interscalene brachial plexus block and causes less HDP in patients undergoing arthroscopic rotator cuff repair.

Comparisons of different general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer.

Anesthetic-induced immunosuppression is of particular interest in tumor surgery. This study aimed to investigate the influence of the 4 most common general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer. 116 patients were randomly divided into 4 groups. Patients in group S were given sevoflurane-based anesthesia. Group P was administered propofol-based anesthesia. The SD group received sevoflurane combined with dexmedetomidine anesthesia. The propofol combined with dexmedetomidine anesthesia (PD) group received PD. Blood samples were obtained at 5 time points: baseline (T0), 1 hour after the start of the operation (T1), end of the operation (T2), 24 hours (T3), and 48 hours (T4) after the operation. Lymphocyte subsets (including CD3+, CD4+, CD8+, and B lymphocytes) and dendritic cells were analyzed by flow cytometry. Blood glucose, norepinephrine, and cortisol levels were measured using ELISA and a blood gas analyzer respectively. In total, 107 patients were included in the final analysis. Immunological indicators, except CD8+ counts, were all decreased in groups S, P, and SD at T1-4 compared with the baseline value, and the counts of CD3+, CD4+, and dendritic cells, as well as CD4+/CD8+ ratios, were significantly higher in the PD group than in the S, P, and SD at T1-3 (P < .05). There were no significant differences between groups P and SD at any observation time point. Intraoperative stress indices, including norepinephrine and cortisol levels, were significantly lower in the PD group than in the other 3 groups at T1-2 (P < .05). These findings suggest that PD as a probably optimal choice can alleviate immunosuppression in patients undergoing flap reconstruction for oral cancer.

Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis

BackgroundManagement of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.MethodsA retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.ResultsAll groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.ConclusionsOur data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.Trial registrationNo registration, retrospective analysis.Graphical

In vitro Antibacterial Effect Study of Plasma-Activated Saline on Mycobacterium Tuberculosis.

This study aimed to investigate the antibacterial effects of plasma-activated saline (PAS) on My-cobacterium tuberculosis (Mtb). We conducted a growth assay on 3 strains of Mtb and an antibiotic sensitivity test on 4 strains of Mtb. Both tests included groups treated with normal saline (NS), PAS, and hydrochloric acid (HCl). The test of antibiotic sensitivity consisted of parallel tests with two concentrations of bacteria suspension: 10-2 and 10-4. The selected antibiotics were rifampicin (RIF), isoniazid (INH), ethambutol (EMB), and streptomycin (SM). The number of bacteria was determined after one month of culture under different conditions. The Kruskal-Wallis test was used to analyze the differences in grouping factors at representative time points. The growth assay indicated that PAS significantly inhibited the growth of 3 strains of Mtb compared with NS and HCl treatment groups. Furthermore, except for the initial observation time point, the remaining three observation time points consistently demonstrate no significant differences between the NS group and the HCl group. The antibiotic sensitivity test of INH, SM, and RIF indicated that PAS could inhibit the growth of antibiotic-resistant Mtb, and the antibiotic sensitivity test of INH and SM with bacterial suspension concentration of 10-2 and SM with bacterial suspension concentration of 10-4 showed statistically different results. The antibiotic sensitivity test of EMB indicated that the growth of Mtb in PAS was slower than that in NS and HCl in both antibiotic-resistant and sensitive Mtb, but there was no statistical difference. The study indicates that PAS contains a significant amount of active substances and exhibits high oxidizability and an acidic pH state. The unique physicochemical properties of PAS significantly delayed the growth of Mtb, compared to the NS and the HCl. PAS not only inhibited the growth of drug-sensitive strains but also significantly enhanced the sensitivity of drug-resistant strains to anti-tuberculosis drugs, which may provide a new therapeutic strategy for the treatment of tuberculosis.

Sustained increase of pinch strength after traction treatment for symptomatic distal interphalangeal joint osteoarthritis

BackgroundSymptomatic distal interphalangeal joint osteoarthritis is a common joint disease that causes hand disability and reduces quality of life. There are few conservative treatment options for this condition. The purpose of this study was to investigate the effect of traction treatment on symptomatic distal interphalangeal joint osteoarthritis. MethodsThis prospective, longitudinal study involved multiple time-series observations and within-subject controls. The most painful distal interphalangeal joints in patients with hand osteoarthritis were treated by daily, 15-min joint traction at home using a finger trap orthosis. The corresponding contralateral digits were used as within-subject controls. The primary outcome measure was two-point pinch strength, and the secondary outcome measures were radiographic findings and treatment adherence. Longitudinal and pairwise comparison analyses of the treated and control digits examined improvements in two-point pinch strength at months 1, 3, and 6 from baseline. The durability of treatment effects after treatment discontinuation was investigated at month 12. ResultsEighteen treated digits and 18 corresponding control digits were eligible for analysis. There was a significant increase in two-point pinch strength after 1-month traction, and this increase was maintained until month 6 despite the absence of radiographic changes. Compared to controls, significant improvement in two-point pinch strength relative to baseline was seen at every observation time point, with a moderate to large effect size. There was no time–treatment interaction. Treatment adherence was high. At months 3 and 6, around 60–80 % of digits were voluntarily treated. Pinch strength was comparable between months 6 and 12, with greater improvement than in the control group. ConclusionJoint traction treatment can improve pinch strength in symptomatic distal interphalangeal joint osteoarthritis. Larger, randomized studies on traction treatment and the effect on hand function are warranted.

Predictive factors for radiation-induced pituitary damage in pediatric patients with brain tumors

Background and purposeMultiple studies demonstrated hypothalamic–pituitary dysfunction in survivors of pediatric brain tumors. However, few studies investigated the trajectories of pituitary height in these patients and their associations with pituitary function. We aimed to evaluate longitudinal changes of pituitary height in children and adolescents with brain tumors, and their association with endocrine deficiencies. Materials and methodsWe conducted a retrospective analysis of 193 pediatric patients (54.9% male) diagnosed with brain tumors from 2002 to 2018, with a minimum of two years of radiological follow-up. Pituitary height was measured using MRI scans at diagnosis and at 2, 5, and 10 years post-diagnosis, with clinical data sourced from patient charts. ResultsAverage age at diagnosis was 7.6 ± 4.5 years, with a follow-up of 6.1 ± 3.4 years. 52.8% underwent radiotherapy and 37.8% experienced pituitary hormone deficiency. Radiation treatment was a significant predictor of decreased pituitary height at all observed time points (p = 0.016, p < 0.001, p = 0.008, respectively). Additionally, chemotherapy (p = 0.004) or radiotherapy (p = 0.022) history and pituitary height at 10 years (p = 0.047) were predictors of endocrine deficiencies. ANOVA revealed an expected increase in pituitary height over time in pediatric patients, but this growth was significantly impacted by radiation treatment and gender (p for interaction = 0.005 and 0.025, respectively). ConclusionCranial irradiation in pediatric patients is associated with impairment of the physiologic increase in pituitary size; in turn, decreased pituitary height is associated with endocrine dysfunction. We suggest that pituitary gland should be evaluated on surveillance imaging of pediatric brain tumor survivors, and if small for age, clinical endocrine evaluation should be pursued.

Effect of epidural dexmedetomidine in single-dose combined with ropivacaine for cesarean section.

Dexmedetomidine has arousal sedation and analgesic effects. We hypothesize that epidural dexmedetomidine in single-dose combined with ropivacaine improves the experience of parturient undergoing cesarean section under epidural anesthesia. This study is to investigate the effect of 0.5µg/kg epidural dexmedetomidine combined with epidural anesthesia (EA) in parturients undergoing cesarean section. A total of 92 parturients were randomly divided into Group R (receiveing epidural ropivacaine alone) Group RD (receiveing epidural ropivacaine with 0.5µg/kg dexmedetomidine). The primary outcome and second outcome will be intraoperative NRS pain scores and Ramsay Sedation Scale. All 92 parturients were included in the analysis. The NRS were significantly lower in Group RD compared to Group R at all observation timepoint (P > 0.05). Higher Ramsay Sedation Scale was found in Group RD compared to Group R (P < 0.001). No parturient has experienced sedation score of 4 and above. No significant difference regarding the incidence of hypotension, bradycardia and nausea or vomiting, Apgar scores and the overall satisfaction with anesthesia was found between Group R and Group RD (P > 0.05). Epidural dexmedetomidine of 0.5µg/kg added slightly extra analgesic effect to ropivacaine in EA for cesarean section. The sedation of 0.5µg/kg epidural dexmedetomidine did not cause mother-baby bonding deficit. Satisfaction with anesthesia wasn't significantly improved by epidural dexmedetomidine of 0.5µg/kg. No additional side effect allows larger dose of epidural dexmedetomidine attempt. This study was registered at www.chictr.org.cn (ChiCTR2000038853).

Noninvasive conservative management of anterior open bite treated with TADs versus clear aligner therapy.

Anterior open bite can be treated non-surgically via molar intrusion using temporary skeletal devices (TAD). Clear aligner therapy (CAT) is recognized as a viable therapeutic modality for non-extraction treatment of adults with mild open bite. This study aimed to compare the treatment effect and mechanisms of open bite closure between patients treated with braces and TADs double arch intrusion and those treated with CAT. Treatment success at T3 was based on 1- positive overbite on ceph; 2- Change in the vertical dimension 3- post treatment POSI score equal to zero. The TAD group includes 18 consecutively treated patients from the main author. The CAT group consisted of 16 selected patients from three different orthodontists. The observation time points were as follows: pretreatment (T1), end of molar intrusion and positive overbite achieved (T2), end of treatment (T3), at least 6-month follow-up (T4). Treatment changes were assessed by cephalometric analysis and frontal intraoral photo. At the end of treatment, 100% of the patient of the TAD group and 78,6% of the CAT group had a posi score of 0. The TAD group showed a significant reduction in vertical measurements (SN-MPA: -1,55° ± 0.41, LAFH: -3,05 ± 0.51mm, U6-PP: -1.48 ± 0.30mm), but the CAT group did not have significant changes for these variables. Both groups had significant increases in overbite from T1 to T3 (TAD: 4,32 ± 0,5mm; CAT: 2,33 ± 0.56mm), and overbite remained stable at T4. The CAT group did not have a significant upper molar intrusion, but a significant extrusion of 1.22 ± 0.42mm of the lower incisor occurred. The TAD group achieved bite closure by upper molar intrusion, lower molar and incisors vertical control, and mandibular plane counterclockwise rotation, resulting in an improved AP and vertical relationship. The CAT group achieved bite closure through the lower incisor extrusion without significant change in the vertical dimension. This study provides relevant information about the skeletal and dental changes of open bite treatment with TADs double arch intrusion. The comparison with a control group treated with CAT confirms known information.

A Symmetric Kernel Smoothing Estimation of the Time-Varying Coefficient for Medical Costs

In longitudinal studies, subjects are repeatedly observed at a set of distinct time points until the terminal event time. The time-varying coefficient model extends the parametric method and captures the dynamic trajectories of time-dependent covariate effects, thus enabling it to describe the potential relationship between the longitudinal variable and the observed time points. In this study, we propose a novel approach to the estimation of medical costs using a symmetric kernel smoothing method in the time-varying coefficient joint model. A smooth function of medical costs is derived by weighting the values of longitudinal data at all distinct observed time points via the combination of the kernel method and the inverse probability weighting method. For the simulation study, we first set up the true functions of time-varying coefficients; we then generated random samples for covariates and censored survival times. Subsequently, the longitudinal data of response variables could be produced. Further, numerical simulation experiments were conducted by using the proposed method and applying R code to the generated data. The estimated results for the parameters and non-parametric functions were compared with different settings. The numerical results illustrate that as the sample size increases, the bias and model-based standard errors decrease, and the performance improves with larger sample sizes. The estimates of functions in the model almost coincide with the true functions, as shown in the figures of the simulation study. Furthermore, the consistency of the obtained estimator is demonstrated via theoretical analysis, and a numerical simulation is performed to illustrate the performance of the proposed estimators. The proposed model is applied to a real-world data set acquired from a multicenter automatic defibrillator implantation trial (MADIT).

Examining the causal effects of exposure to violence on crime among youth involved in the justice system: Experienced, witnessed, and experienced-witnessed violence.

Previous studies on exposure to violence lack a nuanced understanding of the causal effects of different exposure types on offending behaviors. This study, drawing on Pathways to Desistance Study (PDS) data tracking 1354 adjudicated youths aged 14-18 over 7 years, explores the contemporaneous (cross-sectional), acute (after 1 year), enduring (after 3 years), and long-term (after 6 years) causal effects of violence exposure on property and violent offending. The sample, predominantly male (86%), consisted of White (20%), Black (42%), and other (38%) individuals. The generalized propensity score is used to match unbalanced covariates across multiple exposure types, namely noninvolved (n = 392), witnessed (n = 577), experienced (n = 31), and experienced-witnessed violence (n = 305). Results demonstrate the contemporaneous, acute, enduring, and long-term effects of violence exposure on both violent and property offending, with varying durations and strengths across exposure types. The most pronounced risk effects are immediate, diminishing over time and potentially reversing in the long term as youth transition into adulthood. Among exposure types, experienced-witnessed violence exhibits the most potent effects on offending, followed by witnessed violence and then experienced violence-a pattern consistent across the observed time points. Noteworthy is the finding that the impact of violence exposure is more pronounced for violent offending, diminishing more rapidly compared to the effects on property offending.