Main Endpoint Research Articles

Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines.

Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study's aim was to assess the current status of states' OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States. Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher's exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols. Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%). There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.

Developing primary care services for stroke survivors: the Improving Primary Care After Stroke (IPCAS) research programme

Background It is recognised that longer-term needs after stroke may not be well addressed by current services. The aim of this programme of research was to develop a novel primary care model to address these needs and to evaluate this new approach. Objectives The work was divided into three workstreams: development of a primary care model development of a ‘Managing Life After Stroke’ programme (including self-management) for people with stroke evaluation of the effectiveness and cost effectiveness of these interventions. Design The development of the primary care model involved information gathering in the form of literature reviews, patient and public involvement workshops, qualitative studies (interviews and focus groups), a consensus study and a pilot study, all feeding into a multidisciplinary intervention development group that approved the final primary care model. In parallel, a further literature review, consultation workshops with healthcare professionals and patients and public involvement fed into the iterative development of the ‘My Life After Stroke’ programme. In the final phase of the programme, the two interventions were evaluated in a cluster randomised controlled trial, which included a process evaluation and within-trial cost-effectiveness analysis. Setting General practices in the East of England and East Midlands. Participants People with a history of stroke identified from general practice stroke registers. Interventions The Improving Primary Care After Stroke model of primary care delivery. This comprised five components: a structured review; a direct point of contact; improving communication between primary and secondary care; local service mapping; and training of primary care professionals. The ‘My Life After Stroke’ self-management programme for people with stroke comprised an initial individual session, four weekly group-based sessions and a final individual session. Main outcome measures The coprimary end points for the trial were two subscales (emotion and participation) of the Stroke Impact Scale v3.0 at 12 months after randomisation. Secondary outcomes included the Stroke Impact Scale Short Form, the EuroQol-5 Dimension, five level questionnaire, the ICEpop CAPability measure for Adults, the Southampton Stroke Self-Management Questionnaire and the Health Literacy Questionnaire. Data sources General practice records for health economic costing data. Patient questionnaires for outcomes. Results Trial: 46 clusters (general practices) were randomised with 1040 participants. At 12 months, there was a 0.64 (97.5% confidence interval −1.7 to +2.8) improvement in the emotion outcome in the intervention arm compared to the control arm and a 1.3 (97.5% confidence interval −2.0 to +4.6) increase in the participation outcome in the intervention arm compared to control. There was also no evidence of effect of the intervention on short form Stroke Impact Scale, quality of life (EuroQol 5 Dimension 5 level questionnaire), well-being (ICEpop CAPability measure for Adults), Southampton Stroke Self-Management questionnaire or health literacy (Health Literacy Questionnaire). Process evaluation: over 80% of participants received a review. Only a third of patients attended the ‘My Life After Stroke’ course. The direct point of contact service was hardly used. The local directory of services had variable take-up by healthcare professionals. It did not prove possible to support improved communication between primary and secondary care as originally intended. Training fidelity was high. Cost-effectiveness analysis: the intervention increased primary care workload and was associated with a non-significant, higher quality-adjusted life-year at 12 months. The incremental cost per quality-adjusted life-year was £20,863. Limitations There were differences in age, sex and proportion of people from minority ethnic groups in the trial population as compared to a typical general practice stroke register. Uptake of the intervention was variable. Ceiling effects were observed in the primary outcome measure. Follow-up was limited to 12 months. Conclusions This programme of research has reaffirmed the importance of addressing longer-term needs of people after stroke in the community. The most commonly expressed need is fatigue. The primary care model that we developed was not effective at addressing these needs. Our qualitative findings suggest that an intervention focused on patients earlier after their stroke or one which is more intensive might be effective. There was a mismatch between the needs reported by stroke survivors and evidence available for how to address these needs. Future work Research to inform who should be offered poststroke assessment of needs in the community in the longer term (after 6 months). Development and evaluation of interventions to address fatigue, low mood and cognitive problems in people with stroke in the community. Study registration This study is registered as PROSPERO 2015 CRD42015026602. Trial registration This trial is registered as ISRCTNCT03353519. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: PTC-RP-PG-0213-20001) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy: nationwide propensity-score-matched analysis.

Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P < 0.001), less intraoperative blood loss (200 ml versus 500 ml; P < 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P < 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.

Oral anticoagulants increased 30-day survival in sepsis patients complicated with atrial fibrillation: a retrospective analysis from MIMIC-IV database.

The severity of sepsis is associated with systemic clotting activation. Atrial fibrillation (AF) is the most commonly observed arrhythmia in patients with sepsis and can lead to a poor prognosis. The aim of this study is to elucidate the association between oral anticoagulants and survival from septic patients complicated with AF. The data of 8,828 septic patients, including 2,955 AF and 5,873 without AF, were all originated from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients with sepsis and AF are divided into OAC- group (n = 1,774) and OAC+ group (n = 1,181) based on OAC therapy. Septic patients with no AF were considered as the control group (n = 5,873, sepsis and no AF group). The main outcome endpoint was the survival rate of 30 day. The secondary outcome endpoint was the length of stay (LOS) from intensive care unit and hospital. Propensity score matching (PSM) was used to adjust the influence of superfluous factors, and a restricted mean survival time (RMST) analysis was used for calculating the benefit of survival time and survival rate. Analysis including univariate and multivariate logistic regression analysis was conducted to find prognosis-related predictors. After PSM, the OAC+group had a higher 30-day survival rate compared to the OAC- group (81.59% vs. 58.10%; P < 0.001) in the ICU. Despite the higher survival, the hospital LOS (14.65 days vs. 16.66 days; P = 0.15) and ICU LOS (6.93 days vs. 5.92 days; P = 0.02) were prolonged at OAC+ group than OAC- group. No difference was found in survival rate of 30 day between the sepsis patients using warfarin and patients using NOAC (85.60% vs. 79.84%, P = 0.12). The sepsis patients using warfarin had a prolonged LOS in ICU and hospital compared with the sepsis patients using NOAC. In the vasopressor subgroup, patients who received NOAC therapy were associated with a reduced 30-day survival rate (73.57% vs. 84.03%; P = 0.04) and reduced LOS in ICU and hospital than those on warfarin therapy. This study demonstrated that oral anticoagulants may increase the 30-day survival rate of patients with sepsis and AF.

Androgen deficiency is associated with a better prognosis in glioblastoma

BackgroundThe androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown.AimThis study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma.MethodsForty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis.ResultsMost of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004).ConclusionCirculating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main known cause of life-threatening fluoropyrimidine (FP)-induced toxicities. We conducted a meta-analysis on individual patient data to assess the contribution of deleterious DPYD variants *2A/D949V/*13/HapB3 (recommended by EMA) and clinical factors, for predicting G4-5 toxicity. Study eligibility criteria included recruitment of Caucasian patients without DPD-based FP-dose adjustment. Main endpoint was 12-week haematological or digestive G4-5 toxicity. The value of DPYD variants *2A/p.D949V/*13 merged, HapB3, and MIR27A rs895819 was evaluated using multivariable logistic models (AUC). Among 25 eligible studies, complete clinical variables and primary endpoint were available in 15 studies (8733 patients). Twelve-week G4-5 toxicity prevalence was 7.3% (641 events). The clinical model included age, sex, body mass index, schedule of FP-administration, concomitant anticancer drugs. Adding *2A/p.D949V/*13 variants (at least one allele, prevalence 2.2%, OR 9.5 [95%CI 6.7-13.5]) significantly improved the model (p < 0.0001). The addition of HapB3 (prevalence 4.0%, 98.6% heterozygous), in spite of significant association with toxicity (OR 1.8 [95%CI 1.2-2.7]), did not improve the model. MIR27A rs895819 was not associated with toxicity, irrespective of DPYD variants. FUSAFE meta-analysis highlights the major relevance of DPYD *2A/p.D949V/*13 combined with clinical variables to identify patients at risk of very severe FP-related toxicity.

Autologous inclusion technique versus Dacron inclusion technique in modified Ross surgery in adults: a retrospective single-center study

The Ross procedure has been shown to have excellent long-term outcomes. However, pulmonary autografts remain at risk of dilation in the long-term period. Therefore, the autologous inclusion technique (AIT) and the Dacron inclusion technique (DIT) have been developed. No direct comparison up to date has been reported of these two techniques.Aim: To compare immediate and medium-term results performing various modified techniques of the Ross operation.Material and Methods. The following retrospective study included 43 patients (AIT: 22; DIT: 21) aged 18 years and older with an aortic valve (AV) pathology who underwent modified Ross procedures (AIT and DIT) from January 2014 to December 2019, performed by a single surgeon. The main endpoints were: in-hospital mortality, postoperative AV pressure gradients, time of myocardial ischemia and cardiopulmonary bypass, postoperative complications (resternotomy due to bleeding, perioperative myocardial infarction, stroke, sternal infection, conduction disorder requiring implantation of a permanent pacemaker, acute renal failure requiring hemodialysis) and mid-term outcomes (freedom from reoperation, freedom from aortic dilatation ≥ 5 cm). The median follow-up period was 23 (12–68) months.Results. The main indication for surgery was aortic regurgitation in 32 patients (74.4%). Bicuspid aortic valve was diagnosed in 29 (67.4%) patients. There were 33 (76.7%) males with an average age of 40 ± 11.7 years. There were no lethal outcomes in both groups. There was also no significant difference in postoperative complications. The peak and mean gradients on the AV were significantly lower in the AIT group than in the DIT group (6 and 4 mmHg vs 8 and 7 mmHg, p = 0.04). Five-year overall survival, freedom from reoperation on AV and PV, and freedom from dilatation of the ascending aorta ≥ 5 cm after modified Ross operation were 97.4%, 100%, and 100%, respectively. There was no statistically significant difference between groups in terms of overall survival (p = 0.66).Conclusion. Both techniques, autologous inclusion and Dacron inclusion, provide excellent immediate and mid-term outcomes in terms of overall survival, freedom from reoperation and freedom from aortic dilation

Ecological assessment of stream water polluted by phosphorus chemical plant: Physiological, biochemical, and molecular effects on zebrafish (Danio rerio) embryos

The rapid development of the phosphorus chemical industry has caused serious pollution problems in the regional eco-environment. However, understanding of their ecotoxic effects remains limited. This study aimed to investigate the developmental toxicity of a stream polluted by a phosphorus chemical plant (PCP) on zebrafish embryos. For this, zebrafish embryos were exposed to stream water (0, 25, 50, and 100% v/v) for 96 h, and developmental toxicity, oxidative stress, apoptosis, and DNA damage were assessed. Stream water-treated embryos exhibited decreased hatching rates, heart rates, and body lengths, as well as increased mortality and malformation rates. The general morphology score system indicated that the swim bladder and pigmentation were the main abnormal morphological endpoints. Stream water promoted antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx)), lipid peroxidation, and DNA damage. It also triggered apoptosis in the embryos' heads, hearts, and spines by activating apoptotic enzymes (Caspase-3 and Caspase-9). Additionally, stream water influenced growth, oxidative stress, and apoptosis-related 19 gene expression. Notably, tyr, sod (Mn), and caspase9 were the most sensitive indicators of growth, oxidative stress, and apoptosis, respectively. The current trial concluded that PCP-polluted stream water exhibited significant developmental toxicity to zebrafish embryos, which was regulated by the oxidative stress-mediated activation of endogenous apoptotic signaling pathways.

Treating pathological metastatic fractures of the humerus by compound osteosynthesis: a retrospective cohort study

BackgroundThe number of malignant tumors is increasing as are bone metastases, such as those in the humerus. Arm function is important for an independent everyday life. In this study, compound osteosynthesis of metastatic fractures of the humerus is examined for its suitability in light of the competing risk of death. Materials and MethodsThis retrospective monocentric study includes a cohort of tumor patients who underwent primary compound osteosynthesis for pathological humeral fractures. The main endpoint was the continued existence of compound osteosynthesis using competing risk analysis (CRA) to contrast failure and death. Failure was defined as mechanical failure of the osteosynthesis construct like re-fracture or plate-and-screw dislocation or loosening, which provides an indication for re-intervention. Other complications are also described. ResultsWe included 36 consecutive patients (64% male, mean age 71.6 yrs.) from September 2007 to October 2020. In 58% of the cases, the left humerus was fractured. Lung carcinoma was the most common cause of bone metastases (27.8%). Compound osteosynthesis was performed with a median delay of five days after diagnosis of the pathologic fracture. Postoperative complications occurred in seven of the 36 patients (19.4%): radial nerve palsy (n = 3), postoperative hematoma (n = 2), re-fracture (n = 2) and screw loosening (n = 1). Few mechanical failures (8.3%) occurred within the first year; only one patient needed revision of the osteosynthesis (2.8%). Median patient survival after compound osteosynthesis was 26.6 weeks. CRA showed that for up to two years, the risk of death is clearly dominant over the risk of osteosynthesis failure from surgery. ConclusionOur study shows that compound osteosynthesis of the humerus is a suitable option for patients with pathologic humerus fractures. Compound osteosynthesis of the humerus usually survives the duration of malignant tumor disease.

Right ventricular-pulmonary arterial coupling ratio derived from 3-dimensional echocardiography predicts outcomes in systemic lupus erythematosus-associated pulmonary arterial hypertension patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune connective tissue disease (CTD) that is an important cause of devastating pulmonary arterial hypertension (PAH), and persistent progression of PAH can lead to right heart failure, predicting a poor prognosis for SLE patients. Right ventricular-pulmonary arterial (RV-PA) coupling with echocardiography has been demonstrated to be a noninvasive alternative method for evaluating PAH patients' predictive outcomes. Whether the ratio of right ventricular stroke volume (RVSV) to right ventricular end-systolic volume (RVESV) measured by three-dimensional echocardiography (3DE) is a new index of RV-PA coupling has not been discussed as a new predictor for the clinical outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). From June 2019 to February 2023, 46 consecutive patients with SLE-PAH were enrolled prospectively, and their clinical data and echocardiographs were studied and analyzed. The control group consisted of 30 healthy subjects matched for age, sex, and body surface area (BSA). The main endpoints of this study were a composite of all-cause mortality and adverse clinical events. Baseline clinical characteristics and echocardiographic assessments were analyzed. During a median of 24months (IQR 18-31), 16 of 46 SLE-PAH patients (34.7%) experienced endpoint-related events. At baseline, patients who experienced mortality or adverse events had a worse WHO functional class (WHO FC) and lower anti-double-stranded DNA (dsDNA) antibody levels. The right ventricular (RV) systolic dysfunction in SLE-PAH subjects was significantly worse than that in the healthy control group, especially in SLE-PAH patients in the endpoint event group. Compared to controls, patients with SLE-PAH had a lower RVSV/RVESV ratio. In the group comparison, patients who had experienced an endpoint event had a sequentially worse ratio (1.86 (1.65-2.3) versus 1.30 (1.09-1.46) versus 0.64 (0.59-0.67), p < .001). There were statistically significant associations between the RVSV/RVESV ratio to routine RV systolic function and clinical parameters. The RVSV/RVESV ratio was negatively correlated with the WHO FC (r = -0.621, p < .001) and positively correlated with the anti-dsDNA level. The ROC curve showed that the optimal cutoff for RVSV/RVESV < 0.712 determined a higher risk of poor prognosis. Kaplan‒Meier survival curves showed that an RVSV/RVESV ratio >0.712 was associated with more favorable long-term outcomes. The 3DE-derived SV/ESV ratio as a noninvasive alternative surrogate of RV-PA coupling was an eximious indicator for identifying endpoint events in SLE-PAH patients and can provide a diagnostic basis for clinical intervention.

Dietary intervention for tertiary prevention in head and neck squamous cell carcinoma survivors: clinical and translational results of a randomized phase II trial.

There is a strong need for preventive approaches to reduce the incidence of recurrence, second cancers, and late toxicities in head and neck squamous cell carcinoma (HNSCC) survivors. We conducted a randomized controlled trial (RCT) to assess a dietary intervention as a non-expensive and non-toxic method of tertiary prevention in HNSCC survivors. Eligible participants were disease-free patients with HNSCC in follow-up after curative treatments. Subjects were randomized 1:1 to receive a highly monitored dietary intervention plus the Word Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention (intervention arm) or standard-of-care recommendations (control arm). The planned sample size for the event-free survival evaluation (primary endpoint) was not reached, and the protocol was amended in order to investigate the clinical (nutritional and quality-of-life questionnaires) and translational study [plasma-circulating food-related microRNAs (miRNAs)] as main endpoints, the results of which are reported herein. One hundred patients were screened, 94 were randomized, and 89 were eligible for intention-to-treat analysis. Median event-free survival was not reached in both arms. After 18 months, nutritional questionnaires showed a significant increase in Recommended Food Score (p = 0.04) in the intervention arm vs. control arm. The frequency of patients with and without a clinically meaningful deterioration or improvement of the C30 global health status in the two study arms was similar. Food-derived circulating miRNAs were identified in plasma samples at baseline, with a significant difference among countries. This RCT represented the first proof-of-principle study, indicating the feasibility of a clinical study based on nutritional and lifestyle interventions in HNSCC survivors. Subjects receiving specific counseling increased the consumption of the recommended foods, but no relevant changes in quality of life were recorded between the two study arms. Food-derived plasma miRNA might be considered promising circulating dietary biomarkers.

GABAPENTINOIDS IN THE SYMPTOMATIC MANAGEMENT OF CANAL STENOSIS: A COMPARATIVE STUDY ON PAIN RELIEF, AMBULATION, AND SAFETY PROFILE

The multimodal management of canal stenosis is increasing, and inhibitors of central sensitization are playing a crucial role in central sensitization processes. Pregabalin and gabapentin are antiepileptic drugs that reduce presynaptic excitability. The objective of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of canal stenosis.A literature search was conducted in four databases. The inclusion criteria were studies that compared pregabalin or gabapentin with a control group in lumbar canal stenosis. Randomized clinical trials and a comparative retrospective cohort study were included. The main clinical endpoints were VAS/NRS, ODI, and RDQ (Roland Morris Disability Questionnaire) at 2, 4, 8 weeks, and 3 months, adverse events, and walking distance were also collected. Data were combined using Review Manager 5.4 software.Six studies and 392 patients were included. The mean age was 60.25. No significant differences were observed in VAS at 2, 4, and 8 weeks: (MD: 0.23; 95% CI: −0.63-1.09), (MD: −0.04; 95% CI: −0.64 to −0.57), and (MD: −0.6; 95% CI: −1.22 to 0.02). Significant differences were observed in favor of pregabalin with respect to VAS at three months: (MD: −2.97; 95% CI: −3.43 to −2.51). No significant differences were observed in ODI (MD: −3.47; 95% CI: −7.15 to −0.21). Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95%CI 1.28-27.05). Walking distance and RDQ could not be compared, although the results were controversial.Gabapentinoids have not been shown to be superior to other drugs used in the treatment of LSS or to placebo. However, they have shown a higher incidence of adverse effects, improved results in VAS at 3 months, and a slight improvement in ambulation at 4 months in combination with NSAIDs compared to NSAIDs in monotherapy.

Acupuncture as adjunctive treatment for linezolid-induced peripheral neuropathy: a case series report.

The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

Reproductive toxicology: keeping up with our changing world.

Reproductive toxicology testing is essential to safeguard public health of current and future generations. Traditional toxicological testing of male reproduction has focused on evaluating substances for acute toxicity to the reproductive system, with fertility assessment as a main endpoint and infertility a main adverse outcome. Newer studies in the last few decades have significantly widened our understanding of what represents an adverse event in reproductive toxicology, and thus changed our perspective of what constitutes a reproductive toxicant, such as endocrine disrupting chemicals that affect fertility and offspring health in an intergenerational manner. Besides infertility or congenital abnormalities, adverse outcomes can present as increased likelihood for various health problems in offspring, including metabolic syndrome, neurodevelopmental problems like autism and increased cancer predisposition, among others. To enable toxicologic studies to accurately represent the population, toxicologic testing designs need to model changing population characteristics and exposure circumstances. Current trends of increasing importance in human reproduction include increased paternal age, with an associated decline of nicotinamide adenine dinucleotide (NAD), and a higher prevalence of obesity, both of which are factors that toxicological testing study design should account for. In this perspective article, we highlighted some limitations of standard testing protocols, the need for expanding the assessed reproductive endpoint by including genetic and epigenetic sperm parameters, and the potential of recent developments, including mixture testing, novel animal models, in vitro systems like organoids, multigenerational testing protocols, as well as in silico modelling, machine learning and artificial intelligence.

Inetetamab-based therapy in real-world treatment patterns with HER2-positive advanced breast cancer patients: a retrospective single-center study.

Inetetamab is a novel antibody targeting human epidermal growth factor receptor 2 (HER2) developed in China. Due to its optimized antibody-dependent cell-mediated cytotoxicity effect compared with trastuzumab, it has shown good efficacy and safety in the treatment of HER2-positive advanced breast cancer (ABC). This study aimed to investigate the efficacy and safety of inetetamab combination therapy in the treatment of HER2-positive ABC in real-world clinical practice. Retrospective study. A total of 133 patients with HER2-positive ABC who were treated with inetetamab-based regimens between March 2020 and January 2024 were retrospectively included in this study. The main endpoint was median progression-free survival (mPFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The study included 133 HER2-positive ABC patients, and the median age was 55 years. The mPFS was 8.0 (6.7-9.3) months. The ORR was 50.4%, while the DCR was 88.7%. The mPFS for patients receiving inetetamab-based therapy as first to second, third to fourth, and later lines of metastatic treatment were 14.0, 7.0, and 6.0 months, respectively. Patients treated with inetetamab plus pyrotinib plus chemotherapy, especially with capecitabine, had the best outcomes (mPFS = 14.0 months). Multivariate analysis revealed that prior HER2-TKI treatment was significantly associated with worse PFS (hazard ratios 2.829, 95% confidence interval 1.265-6.328, p = 0.011). Subgroup analysis indicated that patients without visceral metastases had significantly better PFS (14.0 months vs 8.0 months, p = 0.003). The overall incidence of any grade adverse events (AEs) was 100%, with most being grades 1-2. Severe complications included neutropenia (37.6%) and leukopenia (33.1%). Inetetamab-based combination therapy shows promising efficacy and good safety in patients with HER2-positive ABC. It is one of the late-line treatment options for Chinese patients with HER2-positive ABC.

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL)

PurposeIlofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety.MethodsIn this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition.ResultsSix hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group.ConclusionAmong critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

Magnesium bioresorbable scaffold (Magmaris) versus polymer biodegradable ultrathin drug-eluting stent (Ultimaster) in acute coronary syndrome. Mid-term outcomes (2 years).

Acute coronary syndrome (ACS) is a well-known risk factor for adverse clinical outcomes in percutaneous coronary intervention (PCI). Therefore, evaluation of coronary stents in this challenging clinical scenario can provide unique information on device safety and efficacy. Bioresorbable scaffolds (BRS) were designed to overcome long-term complications related to permanent vessel caging with a permanent metallic drug-eluting stent (DES). We designed this study to evaluate the mid-term safety and efficiency of the Magmaris BRS in comparison to the leading new-generation ultrathin DES Ultimaster in the ACS population. We present a retrospective analysis of 2-year follow-up data. The primary outcomes consisted of death from cardiac causes, myocardial infarction, and in-stent thrombosis. The second main study endpoint was defined as target-lesion failure (TLF). The study population consisted of two cohorts, the first of 193 patients treated with Magmaris implantation and the second of 169 patients treated with Ultimaster implantation. At the 2-year follow-up, there were no significant differences in both study cohorts in terms of primary outcome (5.1% vs. 11%; p = 0.051), and TLF (5.6% vs. 8%, p = 0.41). Treatment with a second-generation BRS (Magmaris) versus a novel second-generation DES (Ultimaster) in non-ST-elevation acute coronary syndrome (NSTE-ACS) was associated with similar rates of target lesion failure at 2-year follow-up.

Turkish Real Life Atrial Fibrillation in Clinical Practice: TRAFFIC Study.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and is associated with an increased risk of thromboembolism, ischemic stroke, impaired quality of life, and mortality. The latest research that shows the prevalence and incidence of AF patients in Türkiye was the Turkish Adults' Heart Disease and Risk Factors study, which included 3,450 patients and collected data until 2006/07.The Turkish Real Life Atrial Fibrillation in Clinical Practice (TRAFFIC) study is planned to present current prevalence data, reveal the reflection of new treatment and risk approaches in our country, and develop new prediction models in terms of outcomes. The TRAFFIC study is a national, prospective, multicenter, observational registry. The study aims to collect data from at least 1900 patients diagnosed with atrial fibrillation, with the participation of 40 centers from Türkiye. The following data will be collected from patients: baseline demographic characteristics, medical history, vital signs, symptoms of AF, ECG and echocardiographic findings, CHADS2-VASC2 and HAS-BLED (1-year risk of major bleeding) risk scores, interventional treatments, antithrombotic and antiarrhythmic medications, or other medications used by the patients. For patients who use warfarin, international normalized ratio levels will be monitored. Follow-up data will be collected at 6, 12, 18, and 24 months. Primary endpoints are defined as systemic embolism or major safety endpoints (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding as defined by the International Society on Thrombosis and Hemostasis). The main secondary endpoints include major adverse cardiovascular events (systemic embolism, myocardial infarction, and cardiovascular death), all-cause mortality, and hospitalizations due to all causes or specific reasons. The results of the 12-month follow-up of the study are planned to be shared by the end of 2023. The TRAFFIC study will reveal the prevalence and incidence, demographic characteristics, and risk profiles of AF patients in Türkiye. Additionally, it will provide insights into how current treatments are reflected in this population. Furthermore, risk prediction modeling and risk scoring can be conducted for patients with AF.

Cytologic Surveillance Versus Immediate Referral to Colposcopy for Women with a Cervical Cytology Diagnosis of ASC-US and LSIL in the Absence of HPV DNA Test

Background and Objectives: Cytology screening programmes decrease the risk of cervical cancer by detecting the precancerous changes. Treating these reduce the likelihood of developing invasive disease in future. The management strategies for severe precancerous changes are well established, however, this is not the case with minor cytological abnormalities like ASCUS or LSIL especially when a triage strategy like HPV testing is not easily available. This study aims to assess whether immediate referral to colposcopy is better than cytologic surveillance for women with a cervical smear diagnosis of ASC-US and LSIL in a context where HPV test is either unavailable or not affordable. Methods: A prospective study was conducted at a tertiary care hospital between January 2021 and November 2022. Total 126 women with a Pap smear report of ASC-US or LSIL were recruited to receive either cytologic surveillance (Group A) or immediate colposcopy (Group B), with 63 women in each group. Adherence to follow up and eventual histologic diagnosis of HSIL on colposcopically directed biopsy (CDB) and/or Loop electrical excision procedure (LEEP) were considered as the main study end-point. Results: Significantly more women defaulted from the cytologic surveillance group than the immediate colposcopy group (p=0.00001). In group B, using CDB and LEEP, 5 additional high-grade lesions were detected. However, the p value was not significant when compared with the cytologic surveillance group (p=0.360). Interpretation and Conclusions: Cytologic surveillance is fraught with a poor compliance rate. In the absence of HPV DNA test, minor cytologic abnormalities should undergo immediate colposcopy if follow up cannot be ensured. The high persistence rates of ASC-US and LSIL (41.18% and 35.71%), as well as the high progression rate of LSIL in the cytologic surveillance group, also underscore the necessity for these women to undergo immediate referral to colposcopy.

The Effects of Daytime Variation on Short-term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

Study objectiveTo evaluate the effects of time of operation on short-term outcomes of patients undergoing off-pump coronary artery bypass grafting (OPCAB). DesignRetrospective cohort study. SettingA single large-volume cardiovascular center. PatientsPatients undergoing elective OPCAB between September 2019 and July 2022. InterventionsPatients were divided into two groups according to the start time of surgery: morning (AM group, before 11am) and afternoon (PM group, after 11am). Propensity score matching (PSM) with a 1:1 matching ratio was used to create comparable cohorts. Measurements and Main resultsThe primary endpoint was the composite incidence of mortality and morbidities during hospitalization. Secondary endpoints included postoperative bleeding and transfusion, mechanical ventilation duration (MVD) and length of stay (LOS) in intensive care unit (ICU) and hospital. From a consecutive series of 1,039 patients, PSM yielded 317 well-matched pairs. There was no difference in the composite incidence of in-hospital mortality and morbidities between AM and PM groups (16.4% vs. 17.4%, P=0.832). However, patients in PM group were associated with less postoperative blood loss over the first 24 h (470 ml vs. 540 ml, P=0.002), decreased MVD (14 h vs. 16 h, P<0.001) and shorter LOS in ICU (46 h vs. 68 h, P=0.002) as compared to patients in AM group. ConclusionsThe current study suggested a lack of relevance regarding time of operation with in-hospital mortality and morbidities in patients undergoing OPCAB.