Prospective Observation Research Articles

Machine learning methods in prediction of basal cell skin cancer recurrence after photodynamic therapy

Objective: Verification of predictors and forecasting basal cell skin cancer recurrence (BCSC) after conducting photodynamic therapy (PDT) based on machine learning methods (ML).Methods: The prospective study of 170 patients (117 women and 53 men) was conducted. The median age was 68 years. All patients got PDT treatment on BCSC. Potential predictors of BCSC were analyzed. Primary outcome measure was the fact of tumor development recurrence.Results: During 4-year observation period the recurrence of the disease took place in 18 cases (10.6% of patients). Processing and analyzing data with the assistance of machine learning methods (ML) allowed to highlight the predictors connected with the development of BCSC recurrence development linearly and non linearly. There are such predictors as: 2nd stage of the process, its morphea-like form, localization in the thoracic cage area, the level of ESR and glucose in the blood. The most accurate forecast of BCSC recurrence was gotten using model based on multiple linear regression (LR). It was proved by high levels of quality indexes (the area under ROCcurve – 0.893, sensitivity – 0.849, specificity – 0.889). Predictive accuracy of the stochastic gradient boosting model (SGB) was less significant.Conclusions. PDT is an effective BCSC treatment method. It is proved by the results of prospective observation of patients for the period of 4 years. ML methods are an informative tool to verify predictors and forecast BCSC recurrence. Forecasting models based on multiple LR demonstrate much higher accuracy compared with SGB.

Activity of ankylosing spondylitis in women within one year after childbirth

To assess the dynamics of activity of ankylosing spondylitis (AS) during the year after childbirth, to identify predictors of high activity. 75 pregnant with confirmed AS (modified New York criteria, 1984) were included for prospective observation. Of these, 44 women were followed up for 1 year after delivery. The average age of the patients was 32.55.8 years, the duration of the disease was 149.096.3 months. Lactation was established in 40 women and the duration was 10 [4; 12] months. The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) at 1, 6 and 12 months after giving birth was 2.4 [1.4; 4.2], 2.6 [1.4; 4.4] and 2.7 [1.5; 4.1], respectively (p0.05). ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score C-reactive protein) was 2.0 [1.2; 2.7], 1.9 [1.4; 2.5] and 1.7 [1.3; 2.3], respectively (p0.05). There were no differences between the values of BASDAI, ASDAS-CRP between women with and without lactation. Predictors of high AS activity (BASDAI4) 1 month after delivery were: BASDAI4 in the 1st (odds ratio OR 8.1; 95% confidence interval CI 1,837,0) and 2nd trimesters of pregnancy (OR 5.1, 95% CI 1.220.6); NRS back pain 4 in the 2nd trimester (OR 4.3, 95% CI 1.117.2); cancellation of biological disease-modifying antirheumatic drugs therapy in the 1st trimester of pregnancy (OR 21.0, 95% CI 1.0440.9). Predictors of high AS activity in 6 months after delivery were: BASDAI4 in the 1st (OR 6.5, 95% CI 1.528.7), in the 2nd (OR 6.7, 95% CI 1.627.8) and in the 3rd trimesters of pregnancy (OR 8.7, 95% CI 1.938.6); high activity in 1 month after delivery (OR 4.0, 95% CI 1.015.9). AS activity remains stable for 1 year after delivery. High AS activity during pregnancy was a risk factor for high activity within 6 months after delivery.

Temporal Profiles of Symptom Scores After Palliative Radiotherapy for Bleeding Gastric Cancer With Adjustment for the Palliative Prognostic Index: An Exploratory Analysis of a Multicentre Prospective Observational Study (JROSG 17–3)

AimsAlthough palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. Materials and methodsThis study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. ResultsThe present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, −0.26, −0.22 and −0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, −0.25, −0.19 and −0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. ConclusionShortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.

Occupational disease claims and non-occupational morbidity in a prospective cohort observation of nickel electrolysis workers

Exposure to nickel aerosol in the nickel production is associated with greater occupational risk, yet little is known how many workers will develop an occupational disease and claim compensation. The aim of this analysis was to prospectively observe a cohort of nickel electrolysis workers and quantitatively assess confirmed occupational disease claims. We observed a cohort of nickel electrolysis workers (N = 1397, median age 39, 68% males) from 2008 till 2020 in one of the largest nickel producers in the Russian High North. Cumulative incidence of confirmed occupational disease claims in seven occupational groups, including electrolysis operators, hydrometallurgists, crane operators, final product cleaners, metalworkers, electricians and ‘other’ was analyzed and supplemented with Cox proportional hazards regression, yielding hazard ratios (HR) with their 95% confidence intervals (CI) of occupational disease claims for each group. N patients with occupational disease claims varied from 1 in 2016 to 22 in 2009, and in total 87 patients developed one or more occupational diseases (cumulative incidence 6.2%, p < 0.001 between seven groups). Accounting for 35,527 person-years of observation in total, cleaners exhibited the greatest risk (HR 2.58 (95% CI 1.43–4.64)), also adjusted for smoking, number of non-occupational diseases and group 2 (hydrometallurgists). Smoking was independently associated with having an occupational disease claim in all groups (p < 0.001), as was the number of non-work-related diseases in six groups of seven. Despite consistent improvement in the exposure control measures in nickel production, occupational morbidity persists. More effort is needed to reduce exposure in final product cleaners.

Outcomes for patients with severe chronic neutropenia treated with granulocyte colony-stimulating factor

AbstractSevere chronic neutropenia (SCN), defined as blood neutrophils <0.5 × 109/L for >3 months, is an uncommon hematological condition associated with recurrent and severe bacterial infections. After short-term clinical trials showed the benefits of granulocyte colony-stimulating factor (G-CSF) treatment for SCN, SCNIR (Severe Chronic Neutropenia International Registry) opened to determine the long-term benefits and safety of this treatment. This report summarizes findings from more than 16 000 patient-years of prospective observations for patients with congenital and acquired SCN. We observed that adverse outcomes depend on the underlying etiology. Myelodysplasia (MDS) and acute myeloid leukemia (AML) occur infrequently and largely in patients with congenital neutropenias. Having cyclic or chronic autoimmune/ idiopathic neutropenia portends a favorable prognosis. A few patients with idiopathic neutropenia evolve to develop lymphoid malignancies, but they do not appear to be at increased risk of myeloid malignancies, even with very long-term G-CSF therapy. Progression to systemic autoimmune diseases, bone marrow (BM) failure, aplastic anemia, or nonmyeloid malignancies are not expected consequences of SCN or treatment with G-CSF.

The characteristics of the continuously-recorded mechanical power and its associated clinical outcomes in medical patients with respiratory failure (CORE POWER) study: The protocol of prospective observation study.

Background: The amount of energy delivered from the ventilator applied to the lungs within a given timeframe, is defined as mechanical power (MP). Recently, low MP is one of the new concepts in lung-protective ventilation strategies that may associate with survival benefit. However, measuring MP requires additional calculations not being carried-out in usual clinical care and the reports about MP were mostly a cross-sectional data. The real-time changes or dynamic data of MP was scarcely reported. Our objective is to investgate the association between the dynamic changes of MP and clinical outcomes in critically ill patients. Methods: This will be a prospective, observational study performed in a single center. Adult patients admitted to medical intermediate and intensive care units who requiring invasive mechanical ventilation will be consecutively enrolled. The patients’ ventilators will be connected to the specific investigator’s computer system for continuously real-time data recording for at least 24 hours. The primary outcome is in-hospital mortality. Hypothesis: We hypothesize that excessive mechanical power during mechanical ventilation contributes to ventilator-induced lung injury, thus real-time continuously mechanical power monitoring may reduce adverse events associated with mechanical ventilation. Ethic: The study protocol has been approved by the Institution Review Board of Ramathibodi Hospital, Mahidol University, Thailand (No. MURA2021/680). Trial registration: TCTR20220202010

Robotic surgery contributes to the preservation of bowel and urinary function after total mesorectal excision: comparisons with transanal and conventional laparoscopic surgery

BackgroundDetermine whether robotic surgery is more effective than transanal and conventional laparoscopic surgery in preserving bowel and urinary function after total mesorectal excision (TME).MethodsOf 79 lower rectal cancer patients who underwent function-preserving TME between 2016 and 2020, 64 patients consented to a prospective questionnaire-based functional observation study (52 responded). At 6 months post-resection or ileostomy closure, Wexner, low anterior resection syndrome (LARS), modified fecal incontinence quality of life, and international prostate symptom scores were used to evaluate bowel and urinary function, comparing robotic surgery (RTME) with transanal (taTME) or conventional laparoscopic surgery (LTME).ResultsRTME was performed in 35 patients (54.7%), taTME in 15 (23.4%), and LTME in 14 (21.9%). While preoperative bowel/urinary functions were similar in all three procedures, and the distance from the anal verge to tumor was almost the same, more hand-sewn anastomoses were performed and the anastomotic height from the anal verge was shorter in taTME than RTME. At 2 years post-resection, 8 patients (12.5%) had a permanent stoma; RTME showed a significantly lower rate of permanent stoma than taTME (2.9% vs. 40%, p < 0.01). Despite no significant difference, all bowel function assessments were better in RTME than in taTME or LTME. Major LARS was observed in all taTME and LTME cases, but only 78.8% of RTME. No clear difference arose between RTME and taTME in urinary function; urinary dysfunction was more severe in LTME than RTME (36.4% vs. 6.1%, p = 0.02).ConclusionsIn function-preserving TME for lower rectal cancer, robotic surgery was suggested to be more effective than transanal and conventional laparoscopic surgery in terms of bowel and urinary functions.

Responses To Low Dose Propranolol In Haemodynamic Changes Produced By Stress During Surgery

Introduction: Anxiety is considered as a major complaint in majority of the patients who are supposed to consult with surgeons for a possible surgical procedure and also as an effective and preventing factor in patients’ resistance to surgical procedures. Preoperative anxiety and its associated problems such as severe changes in hemodynamic parameters, the occurrence of arrhythmia with occasional dangerous hemodynamic complications are more common during anesthesia. Objective: To assess the effects of low dose propranolol to haemodynamic Changes produced by Stress during Surgery. Materials and Methods: A prospective observation study was carried out at the Dept. of Anesthesia, 250 Bedded General Hospital, Noakhali, Bangladesh from January to December 2021. Ninety (90) patients of ASA physical status admitted in hospitals for abdominal diseases had undergone operation of an average duration of 30 to 60 minutes under general anesthesia were selected for the study. Both male and female patients within age group 18-65 years were included. The anaesthetic procedures were explained and reassured to each patient after arrival of patient in operation theatre. Intravenous access was secured. Results: In our study both groups were homogenous as regard to age, weight, height and ASA physical status. The duration of surgery was also statistically matched with each other. The effects of placebo and propranolol on heart rate, systolic arterial pressure and rate pressure product immediately after intubations and during pre-operative period showed significant differences than that of base line values.It was shown the baseline values of heart rate of the two groups were similar. Base line systolic arterial pressures (SAP) were also similar. But it was significantly different within groups. Heart rate was significantly higher in placebo group (Group A) immediately after intubation and at 5, 15, 30, 60 minutes of per-operative period compared to the propranolol group (Group B). .....

Features and changes in retinal nerve fiber layer thickness in high myopic ocular hypertension: a 1-year prospective follow-up.

To observe the features and changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in highly myopic ocular hypertension (HM-OHT) patients. Prospective observation study. Individuals who met the inclusion criteria were recruited into three groups: the healthy high myopia (HM), non-highly myopic ocular hypertension (OHT) and HM-OHT group. The spherical equivalent refraction, axial length, intraocular pressure, central corneal thickness and pRNFL thickness were collected and compared between groups. The OHT and HM-OHT group were followed up for 12 months. The changes in pRNFL thickness across the follow-up times were analyzed. The study included 92 subjects. The mean pRNFL thicknesses were 102.5 ± 11.1μm in the HM (31 people), 101.9 ± 11.7μm in the OHT (34 people) and 102.2 ± 12.0μm in the HM-OHT group (27 people). There was no statistical difference in the mean pRNFL thickness among the three groups. The HM-HOT group and HM group had thicker temporal sectoral (p < 0.05) pRNFL thickness and thinner superior sectoral (p = 0.015) pRNFL thickness than the OHT group. During the 12-month follow-up, the mean pRNFL thickness of the HM OHT group decreased, with an annual reduction of -0.93 ± 0.14μm. There was a significant difference across the three visits (p < 0.05), while there were no significant differences in the OHT group (p = 0.591). After ocular magnification correction, the HM-OHT group did not have thinner pRNFL thickness than the other two groups. However, the thickness decreased significantly over time.

Long-Term Exposure to Essential Oils and Cardiopulmonary Health from a Population-Based Study

It is still unknown whether long-term inhalation of indoor air pollutants from ambient essential oil is associated with increased cardiopulmonary events. We recruited 200 healthy homemakers to conduct a prospective observation study in Northern Taiwan. We measured heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), peak expiratory flow rate (PEFR), and indoor air pollutants four times per year for each participant between 2008 and 2018. Moreover, a questionnaire related to essential oil usage, home characteristics, and health status was filled out with each participant. The association between essential oil usage and cardiopulmonary health was determined using mixed-effects models. The mixed-effects models showed a significant association between essential oil usage and adverse cardiopulmonary effects including increased HR and BP and decreased % predicted PEFR among participants with heavy use of essential oils. No significant association between essential oils usage and adverse cardiopulmonary effects was observed among participants without essential oils usage or participants with mild use of essential oils (less than one hour per day). We concluded that exposure to indoor air pollution related to essential oils was associated with adverse cardiopulmonary effects among participants with essential oil usage more than one hour per day.

Correlation of platelet indices with the spectrum of acute coronary syndrome and extent of coronary artery disease

Platelets have a major role in acute coronary syndrome and their activation is a hallmark of this. Troponin I, Troponin T and Creatine Kinase enzymes are not enough sensitive at an early stage of acute coronary syndrome. Platelet indices can be detected earlier, inexpensive, widely available and easily recordable in most clinical laboratories, thus could be a better marker in these patients. The primary objective of this study is to determine the correlation between platelet indices and spectrums of acute coronary syndrome or the number of vessels involved. This is a prospective observation study conducted in a tertiary care teaching hospital of eastern India over a period of six months where 125 patients were non-randomly selected with a diagnosis of acute coronary syndrome who underwent coronary angiogram and reports correlated with platelet parameters. A total of 100 patients were finally evaluated. Only platelet large cell ratio and platelet-crit were significantly higher in ST elevated myocardial infarction group compared to the unstable angina group. Across all the spectrums of acute coronary syndrome or extent of coronary artery disease there was a strong positive correlation within platelet distribution width, mean platelet volume and platelet large cell ratio, which was also very significant. Similarly total platelet count had a strong positive and very significant correlation with platelet-crit in the above groups. Increase platelet large cell ratio and platelet-crit seems to be independent risk factors for development of ST elevated myocardial infarct than unstable angina. Thus they could serve as simple but important early biomarkers for predicting development of ST elevated myocardial infarction compared to unstable angina in acute coronary syndrome patients.

Клинические варианты периферических увеитов у детей и их осложнения

Purpose. To study the frequency and structure of complications of peripheral uveitis (PU) in children who were hospitalized in the Khabarovsk branch of The S. Fyodorov Eye Microsurgery Federal State Institution in the period from 2015 to 2020. Material and methods. The object of the study were 20 children (40 eyes) with bilateral chronic recurrent PU. In addition to standard examination methods, optical coherence tomography (OCT) was performed. And to clarify the etiological diagnosis of PU, laboratory examinations and examinations by specialists of a narrow profile were carried out. Results. The results of enzyme immunoassay showed the presence of IgG to the herpes simplex virus in 14 patients (70 %), IgG to the Epstein-Barr virus - 12 patients (60 %), IgG to cytomegalovirus – 15 patients (75 %). Two children were found to be infected with Toxoplasma gondii (IgG) and Chlamydia trachomatis (IgG). The results obtained show a significant role of herpesvirus infections in the development of PU in children. In a prospective observation, the most common complication was unilateral or bilateral complicated cataract (8 eyes – 20 %). In 4 eyes – 10 %, according to OCT, cystic macular edema was detected. Traction retinal detachment was diagnosed in 2 eyes of one 15-year-old child. Conclusion. It was found that the main etiological cause of PU was herpesvirus infection. Complicated cataract was the most frequent complication of PU (20 %). The results of the conducted studies are of practical importance for the development of rational treatment tactics in children with PU. Keywords: peripheral uveitis, complications, childhood, etiology.

Defining and Describing Terminal Ulcers in Adults at End of Life: An Integrative Review.

The authors identify and synthesize the published primary literature on unavoidable skin breakdown and end-of-life wounds known as terminal ulcers. Sources were identified through a systematic search of the Cochrane Library, Medline, ProQuest, EMBASE, CINAHL complete, and PubMed databases. The date limiters were set between 1984 and 2020 to locate primary qualitative, quantitative, and/or mixed-methods studies on terminal ulcers. Investigators examined 180 sources and ultimately included four quantitative studies in this review. All were conducted in the US and published between 1989 and 2019. Retrospective chart audits of deceased patients' medical files were undertaken in three of the studies, and prospective observations were used in the fourth. Descriptive and inductive content analyses were conducted. Three categories emerged: (1) distinguishing the ulcer development patterns, (2) identifying the ulcer characteristics, and (3) delivering specialized and individualized end-of-life care. Limited primary evidence has been published on terminal ulcers. Pressure injuries and terminal ulcers have similar appearances, but their development differs significantly. The lack of a specific terminal ulcer assessment tool and staging system increases the risk of these unavoidable end-of-life wounds being incorrectly assessed and managed as pressure injuries. Further research on terminal ulcers is needed to inform clinical practice and ensure specialized care is delivered to patients who develop these wounds.

CYFRA 21-1 Predicts Progression in Idiopathic Pulmonary Fibrosis: A Prospective Longitudinal Analysis of the PROFILE Cohort.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. Objectives: To determine the relationship between serum concentrations of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) study. Methods: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung obtained at surgery. Concentrations of CYFRA 21-1 were measured using an ELISA-based assay in serum samples collected at baseline, 1 month, and 3 months from 491 individuals with an incident diagnosis of IPF who were enrolled in the PROFILE study and from 100 control subjects at baseline. Study subjects were followed for a minimum of 3 years after their first blood draw. Measurements and Main Results: CYFRA 21-1 localizes to hyperplastic epithelium in IPF lung tissue. Peripheral CYFRA 21-1 concentrations were significantly higher in subjects with IPF than in healthy control subjects in both the discovery (n = 132) (control: 0.96 ± 0.81 ng/ml; vs. IPF: 2.34 ± 2.15 ng/ml; P < 0.0001) and validation (n = 359) (control: 2.21 ± 1.54 ng/ml; and IPF: 4.13 ± 2.77 ng/ml; P < 0.0001) cohorts. Baseline concentrations of CYFRA 21-1 were able to distinguish individuals at risk of 12-month disease progression (C-statistic, 0.70; 95% confidence interval, 0.61-0.79; P < 0.0001) and were predictive of overall mortality (hazard ratio, 1.12 [95% confidence interval, 1.06-1.19] per 1 ng/ml increase in CYFRA 21-1; P = 0.0001). Furthermore, 3-month change in concentrations of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. Conclusions: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.

Epidemiological surveillance of intravascular catheter-related infections in the multidisciplinary healthcare setting: problems and solution ways

The issue of prevention and treatment of healthcare-associated infections (HCI), and in particular intravascular catheter-related infections associated with (ICRI), still remains unresolved. The purpose of the work was to determine the shortcomings in the epidemiological surveillance (ES) for ICRI and the ways to correct them, with the further development of an effective system of ES for ICRI in multidisciplinary healthcare settings. In 2019‒2020, a comprehensive epidemiological study was conducted. It was conducted on the basis of the surgical and intensive care units in multidisciplinary healthcare settings. The study included a retrospective epidemiological analysis of 160 medical records of inpatients on the use of intravascular catheters, a cross-sectional epidemiological study of the use of intravascular catheters, prospective epidemiological observation of 94 patients with intravascular catheters (n=149), a cross-sectional epidemiological study of the level of knowledge, attitude and practice of using intravascular catheters and adherence to infection control rules of 123 healthcare workers (HCW). No cases of catheter-related phlebitis or other ICRI were documented in the medical records of inpatients. An analysis of the completeness of the documentation of the catheterization procedure revealed that in 100% of cases, the probable duration of catheterization, the results of daily observation of the catheterization site, information about the change of dressings and washing of the vascular catheter were not routinely recorded. HCW have an insufficient level of knowledge about epidemiological features, infection control and prevention of ICRI. The majority of HCW (80.0±3.65%) feel the need to receive additional information regarding possible complications of vascular catheterization, infection control, and prevention of ICRI. Taking into account the mentioned shortcomings, a system of ES for ICRI in the multidisciplinary healthcare setting was developed. It includes three structural modules: informational, diagnostic and management. The developed ES system according to the ICRI is suitable for use in multidisciplinary healthcare settings and can be adapted according to the material and technical capacity of the healthcare settings. Keywords: infection control, catheter-related phlebitis, catheter-related bloodstream infections, epidemic situation.

Multicenter prospective observational study of fungal keratitis in Japan: analyses of in vitro susceptibility tests for combinations of drugs.

To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan. Multicenter prospective observational study. Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied. Specially manufactured minimum inhibitory concentration (MIC) measurement plates were used to test the effectiveness of 10 combinations of two antifungal drugs against the isolates. The combinations were pimaricin (PMR) + voriconazole (VRCZ), PMR + fluconazole (FLCZ), PMR + miconazole (MCZ), PMR + micafungin (MCFG), VRCZ + FLCZ, VRCZ + MCZ, VRCZ + MCFG, VRCZ + amphotericin-B (AMPH-B), MCZ + FLCZ, and MCZ + MCFG. The checkerboard microdilution method was used, and the fractional inhibitory concentration (FIC) index was calculated based on the guidelines of The Clinical & Laboratory Standards Institute (CLSI). In yeast-like fungi,additive effects were observed between PMR and MCFG in 77.8% of the isolates, and they were also observed between the azoles. Synergistic effects were observed on 11.1% of the isolates for MCZ and FLCZ. On the other hand, antagonistic effects were present between PMR and azoles with 88.9% between PMR and VRCZ, 72.2% between PMR and FLCZ, and 94.4% between PMR and MCZ. In filamentous fungi,additive effects were observed between PMR and MCFG in 40.9% of the isolates, and between VRCZ and MCZ in 40.9% of the isolates. Antagonistic effects were observed for PMR and the azoles. The combination of drugs prescribed for fungal keratitis incurs a possibility of synergistic, additive, indifferent, or antagonistic effects, depending on drug combinations and fungal strains.

Predictors of Positive Surgical Margins after Robot-Assisted Partial Nephrectomy for Localized Renal Tumors: Insights from a Large Multicenter International Prospective Observational Project (The Surface-Intermediate-Base Margin Score Consortium).

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3–4.2) cm and median (IQR) PADUA score was 8 (7–9). SIB scores of 0–2 (enucleation), 3–4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3–4) versus enucleation (SIB score 0–2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25–7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon’s experience on margin status after robotic PN.

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).

BackgroundAtrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively).MethodsEchocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61–80 bpm, 81–110 bpm, and >110 bpm.ResultsA total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61–80 bpm group: hazard ratio, 0.66; 95% CI, 0.46–0.94; p = 0.021; 81–110 bpm group: hazard ratio, 0.60; 95% CI, 0.40–0.90; p = 0.013). Especially, HFpEF patients with HR 81–110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011).ConclusionIn patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

Effects of a Supplement Containing a Cranberry Extract on Recurrent Urinary Tract Infections and Intestinal Microbiota: A Prospective, Uncontrolled Exploratory Study.

Aim:Cranberries (Vaccinium macrocarpon) are traditionally used in prevention of urinary tract infections (UTIs). The authors' aim was to evaluate effects of a supplement containing cranberry extract, pumpkin seed extract, vitamin C, and vitamin B2 on recurrent uncomplicated UTIs in women and their intestinal microbiota.Methods:A prospective, uncontrolled exploratory study was conducted in women with recurrent uncomplicated UTIs. The primary exploratory outcome was the number of UTIs in a 6-month prospective observation period compared with a 6-month retrospective period. Further outcomes included number of antibiotics, quality of life (SF-36), intestinal microbiota (assessed by 16S rRNA amplicon sequencing), and evaluation questions. Parameters were assessed at baseline and after 1, 2, and 7 months (start of intake of cranberry supplement after 1 month for 6 months). p-Values were calculated with the pairwise Wilcoxon signed-rank test for α diversity and permutational multivariate analysis of variance.Results:Twenty-three women (aged 52.7 ± 12.4 years) were included in the study. Participants reported 2.2 ± 0.8 UTIs (at baseline) in the previous 6 months. After 6 months of cranberry intake, participants reported a significant decrease to 0.5 ± 0.9 UTIs (p < 0.001). Number of antibiotic therapies was also significantly (p < 0.001) reduced by 68% during 6 months of cranberry intake (0.14 ± 0.35) when compared with 6 months retrospectively (1.14 ± 0.71). The SF-36 physical component score increased from 44.9 ± 5.5 at baseline to 45.7 ± 4.6 at 7 months (p = 0.16). The SF-36 mental component score decreased slightly from the baseline value of 46.5 ± 6.5 to 46.2 ± 6.4 at 7 months (p = 0.74). No significant intragroup mean changes at genus, family, or species level for α and β diversity within the intestinal microbiota were found. In the evaluation questions, participants rated the cranberry extract positively and considered it beneficial. The supplement intake was safe.Conclusions:This study shows that women with recurrent uncomplicated UTIs benefit from cranberry intake. Future larger clinical studies with further investigation of the mechanisms of action are required to determine the effects of cranberries on participants with uncomplicated UTIs.

SOX combined with intraperitoneal perfusion of docetaxel compared with DOS regimen in the first-line therapy for advanced gastric cancer with malignant ascites: a prospective observation

ObjectiveThis study aimed to verify the survival superiority of the combination of intraperitoneal perfusion and systemic chemotherapy over standard systemic chemotherapy.MethodsA total of 78 advanced gastric cancer patients with malignant ascites were randomly divided into D-SOX group (intraperitoneal infusion of docetaxel 30 mg/m2 on d1 and d8, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14) and DOS group (intravenous docetaxel 60 mg/m2 on d1, intravenous oxaliplatin 100 mg/m2 on d1, and oral administration of S-1 on d1-d14). Efficacy of both groups was evaluated every 2 cycles with 21 days as a cycle. The primary endpoint was overall survival, and the secondary endpoints were objective response rate, ascites control rate, negative conversion rate of ascites cytology, and side effects.ResultsThe median overall survival in D-SOX group was significantly higher than that in the DOS group (11.7 vs 10.3 months, HR 0.52, 95%CI 0.31–0.86, P = 0.005). The ascites control rate in the D-SOX group was 58.9% and 30.8% in DOS group (95%CI 42.8–75.1% vs 95%CI 15.6–45.9%, P = 0.012). Besides, the adverse reactions were tolerable in both groups, and patients in the D-SOX group had lower grade 3/4 blood toxicity than that in the DOS group (26% vs 54%, P = 0.01).ConclusionCompared with traditional systemic chemotherapy, docetaxel intraperitoneal infusion combined with chemotherapy has better therapeutic effect on gastric cancer ascites, with better survival benefit and tolerance and less hematological toxicity, which is worthy of further research and clinical application.