New-onset Diabetes Mellitus after EUS-guided Drainage with LAMS: A Pilot Study.

BACKGROUND AND AIMS: Walled-off necrosis (WON) is a serious complication of severe pancreatitis, patients with necrotizing pancreatitis having an increased risk of developing diabetes mellitus (DM). The aim of this study was to assess the frequency of new-onset diabetes (NOD) in patients with symptomatic WON after endoscopic ultrasound (EUS)-guided drainage with lumen-apposing metal stents (LAMS). METHODS: We retrospectively analyzed a prospectively collected database of patients with symptomatic WON treated by EUS-guided drainage with LAMS in a tertiary referral center. The patients were followed-up for at least 12 months after stent removal. These patients were compared with age- and sex-matched asymptomatic WON controls without interventional treatment and healthy controls to assess the one-year occurrence of DM. Diabetes was defined according to the American Diabetes Association criteria. RESULTS: Of the 50 patients with symptomatic WON included in the study (male/female ratio, 33:17; median age, 60 years), 13 patients (26%) had pre-existing DM and were excluded. Ten of the remaining 37 patients (27%) without prior DM developed NOD within one year after stent removal, this frequency being higher than in asymptomatic WON controls (18.9%, p=0.581) and healthy controls (2%, p = 0.002). In the symptomatic WON group, NOD patients compared to non-DM patients were older (63.5 vs. 56 years old, p=0.042), had more frequent necrosis > 50% of the pancreatic parenchyma (p=0.002) and had a body-tail location of WON (p<0.001). On multivariate analysis, the number of direct endoscopic necrosectomy (DEN) sessions was the only significant factor for NOD occurrence (OR=7.05, p=0.010). NOD patients had poor glycemic control and required more DEN sessions to achieve WON resolution than patients with prior DM (p=0.017). CONCLUSIONS: In patients with symptomatic WON treated by EUS-guided drainage, DM occurred in 27% of previously non-diabetic patients within one year of follow-up. Patients with extensive pancreatic necrosis were more likely to develop NOD, a high number of DEN sessions being a significant risk factor for NOD occurrence.

Killer Cell Immunoglobulin-like Receptor Genotypes and Reproductive Outcomes in a Group of Infertile Women: A Romanian Study.

A growing body of evidence suggests that endometrial immune disorders may be responsible for endometrial dysfunctions that can lead to gynecological and obstetrical pathology. The aim of this study was to explore the potential relationship between different killer cell immunoglobulin-like receptor (KIR) genotypes and reproductive outcomes. We conducted a prospective cohort study that included 104 infertile patients undergoing an in vitro fertilization procedure. All participants underwent clinical and ultrasound examination, genetic evaluation (KIR genotyping), endometrial washing fluid sampling for cytokine determination, endometrial tissue sampling for histologic assessment and hysteroscopic evaluation. Our analysis showed statistically significant lower levels of uterine cytokines TNF-α (p = 0.001) and IL-1beta (p = 0.000) in the KIR AA genotype group as compared to KIR AB and BB among study participants with chronic endometritis. The study results suggest that the KIR AA genotype population subgroups may be more susceptible to developing endometrial disorders such as chronic endometritis. The changes in the behavior of NK cells seem to be subtle and expressed as an altered regulatory pattern.

Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease. This study explored the association between human leukocyte antigen (HLA) and ESRD. The interaction between genetic and environmental factors may also play a role in the development of ESRD. The study included 2392 ESRD patients who were awaiting renal transplantation. Blood samples were genotyped by SSOP and SSP-PCR methods. Multivariate logistic regression analysis showed that HLA-A*11 (p = 0.027), HLA-A*34 (p = 0.017), HLA-A*69 (p = 0.012), HLA-B*41 (p < 0.001), HLA-B*50 (p = 0.004), HLA-DRB1*10 (p = 0.027), and HLA-DRB1*14 (p = 0.004) were positively associated with ESRD (OR > 1); HLA-DRB1*07 (p < 0.001), HLA-DRB1*08 (p = 0.005), and HLA-DRB1*13 (p < 0.001) were protective against ESRD (OR < 1); and the three-locus haplotype HLA-A*02-B*41-DRB1*03, containing one susceptible allele, was strongly associated with ESRD (p < 0.001, OR = 3.15). In conclusion, this retrospective analysis of HLA typing in patients with ESRD of various etiologies suggests that molecular data on the HLA polymorphism should be collected in order to identify high-risk ESRD patients and to improve graft survival after kidney transplantation.

Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia-Reperfusion Injury.

Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia-reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

Implications of Circadian Rhythm in Stroke Occurrence: Certainties and Possibilities.

Stroke occurrence is not randomly distributed over time but has circadian rhythmicity with the highest frequency of onset in the morning hours. This specific temporal pattern is valid for all subtypes of cerebral infarction and intracerebral hemorrhage. It also correlates with the circadian variation of some exogenous factors such as orthostatic changes, physical activity, sleep-awake cycle, as well as with endogenous factors including dipping patterns of blood pressure, or morning prothrombotic and hypofibrinolytic states with underlying cyclic changes in the autonomous system and humoral activity. Since the internal clock is responsible for these circadian biological changes, its disruption may increase the risk of stroke occurrence and influence neuronal susceptibility to injury and neurorehabilitation. This review aims to summarize the literature data on the circadian variation of cerebrovascular events according to physiological, cellular, and molecular circadian changes, to survey the available information on the chronotherapy and chronoprophylaxis of stroke and its risk factors, as well as to discuss the less reviewed impact of the circadian rhythm in stroke onset on patient outcome and functional status after stroke.

Music as Add-On Therapy in the Rehabilitation Program of Parkinson's Disease Patients-A Romanian Pilot Study.

Music has been proven to have therapeutic potential in neurological disorders, especially Parkinson's disease (PD), since rhythmic auditory cueing can partially replace the progressive loss of rhythmicity and automaticity. Several reports have highlighted improvements in motor outcomes in PD patients undergoing music therapy, but only a few studies have evaluated non-motor outcomes, such as quality of life (QoL), which deteriorates with disease progression. The current pilot study aims to examine the effects of a multimodal rehabilitation program centered on physical therapy combined with listening to music on self-reported QoL in people with PD, compared to the same rehabilitation program alone. The study was conducted on patients with idiopathic PD who attended a specific rehabilitation program with a duration of 2.5 h daily for 14 days. The patients were divided into the study group (16 patients), who listened to background music during the rehabilitation program sessions, and the control group who did not listen to music during sessions. The patients were assessed using the self-report Parkinson's Disease Questionnaire (PDQ-39) at the beginning of the program and 1 month after its initiation. The patients in the study group registered greater improvements in five of the eight areas of life assessed by PDQ-39 compared to the control group. In conclusion, listening to music combined with a multimodal rehabilitation program centered on physical therapy may be beneficial for the patients' quality of life.

Partnering bevacizumab with irinotecan as first line-therapy of metastatic colorectal cancer improves progression free survival-A retrospective analysis.

Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase.

Doubling the Dose of Bevacizumab Beyond Progression in Metastatic Colorectal Cancer-the Experience of a Tertiary Cancer Center.

Background: Colorectal cancer (CRC) is the third most common cancer in Europe, with an annual increase in incidence ranging between 0.4 and 3.6% in various countries. Although the development of CRC was extensively studied, limited number of new therapies were developed in the last few years. Bevacizumab is frequently used as first- and second-line therapy for management of metastatic CRC (mCRC). The aim of this study is to present our experience with using bevacizumab beyond disease progression at different dosage levels in mCRC patients, in terms of overall survival, progression-free survival, time to treatment failure, and toxicities. Methods: We performed a consecutive retrospective analysis of patients with confirmed mCRC who were treated with bevacizumab at "Prof Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania. We included patients who had received bevacizumab as first- or second-line therapy and further stratified them according to the dose administered as a second-line (either standard dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, or double dose of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks-depending on the classical chemotherapy partner). All patients had received bevacizumab beyond progression (BYP) which is defined as continuing bevacizumab administration through second-line treatment despite disease progression. In each group, we evaluated the prognostic factors that influenced survival and treatment outcome. Results: One hundred and fifty-one (151) patients were included in the study. Themedian age of patients receiving double dose bevacizumab (DDB) and standard dose bevacizumab (SDB) was 58 years (range 41-71) and 57 years (range 19-75), respectively. The median overall survival in the DDB group was 41 months (range 27-49) compared to 25 months (range 23-29) in the SDB group (p = 0.01 log-rank test). First-line oxaliplatin-based treatment was used more frequently regardless of group, while irinotecan-based more frequently used as a second-line treatment (p = 0.014). Both oxaliplatin- and irinotecan-based regimens were found to be suitable partners for BYP. Statistical analysis revealed that dose intensity, primary tumor location, and cumulative exposure to BYP had significant influence on survival. Conclusion: Doubling the dose of bevacizumab after first progression may improve survival in mCRC patients. Increasing bevacizumab dose intensity could override the prognostic impact of primary tumor location in patients receiving double the dose of bevacizumab after first disease progression.

Treatment beyond progression in metastatic colorectal cancer: to double or not to double the dose of bevacizumab?

PURPOSE: Bevacizumab or cetuximab represent the standard treatment in association with classical chemotherapy in confirmed metastatic colorectal cancer (mCRC). Bevacizumab could be continued after the first disease progression with an overall survival (OS) advantage, compared to chemotherapy alone, but the optimal dose remains a debatable issue. METHODS: In a retrospective analysis of mCRC patients treated with bevacizumab, we selected patients with administration beyond progression, and stratified them according to the dose received- same dose bevacizumab (SDB) as first-line chemotherapy or double dose bevacizumab (DDB). For each group we evaluated OS, time to treatment failure (TTF) and progression-free survival in the first-line (PFS1) and in the second-line (PFS2). RESULTS: In the first-line therapy, oxaliplatin backbone regimen was used in 73% SDB, compared with 22.5% DDB patients, while irinotecan was used in 75% DDB and 27% SDB patients. Second-line oxaliplatin was given to 50% DDB and 29.7% SDB patients, while irinotecan was administered to 47.5% DDB and 70.3% SDB patients. The median values were: OS - 41 months in the DDB group and 25 months in the SDB group (p = 0.01); TTF - 24 months in the DDB group and 19 months in the SDB group (p=0.009); PFS1 - 17 months in the DDB group and 12 months in the SDB group (p=0.008); PFS2 - 9 months in the DDB group and 5 months in the SDB group (p = 0.03). CONCLUSIONS: Doubling the dose of bevacizumab at progression seems to provide OS and PFS advantage for mCRC patients.

Gastric cancer: adjuvant chemotherapy versus chemoradiation. A clinical point of view.

Gastric cancer represents one of the most severe cancers with poor overall survival. Despite the availability of published data on the efficacy of adjuvant treatment, the actual percentage of treated patients remains low. The toxicity of radiotherapy or chemotherapy regimens differ and clinicians need accessible tools in order to better select candidates for adjuvant treatment. In this review, we present published data from clinical trials and cancer registries that might be useful for properly balancing the efficacy and toxicity of adjuvant treatment in gastric cancer patients who underwent surgery with curative intent.

A brief history of the evolution of the medical research article.

Given the current importance of publishing medical research articles in high-impact international journals, this article briefly presents key moments in the evolution of this reporting genre for a better understanding of the diachronic changes that have shaped it into a highly useful tool for creating and spreading knowledge, as well as for establishing academic hierarchies at both individual and institutional level. Therefore, focus will be placed not only on the evolution of its structure and purpose, but also on issues such as knowledge construction, knowledge claims, writer-reader interaction and the appropriate writing conventions and rhetorical strategies required for successful scientific communication.