Neutrophil-to-Lymphocyte Ratio (NLR) as a Poor Predictive Biomarker for Pathological Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Prospective Study

Background: The literature is inconsistent for the role of neutrophil-to-lymphocyte ratio (NLR) obtained before neoadjuvant therapy (pre-NLR) in predicting pathological response to neoadjuvant chemoradiation (neoCRT) in patients with locally advanced rectal cancer (LARC). In the present cohort study, we explored the predictive role of pre-NLR in this setting. Methods: We prospectively included patients with LARC who were candidates for neoCRT at the Shohada-e-Hafte Tir Hospital (Tehran, Iran) between Mar 2018 and Feb 2020. The pre-NLR was obtained through a peripheral blood smear before CRT. We used the AJCC system for evaluating tumor regression grade (TRG). The TRGs were categorized into: response-group 1 (TRG 0-1 vs. 2-3), response-group 2 (TRG 0 vs. 1-3), and response-group 3 (TRG 0-2 vs. 3). We applied receiver operating characteristic (ROC) analysis to assess the predictive value of pre-NLR. Results: Of the 86 screened patients with rectal cancer, 30   patients who fulfilled the inclusion criteria were included in the study. In total, 63.3% were responsive, and 23.3% had complete pathologic response. Pre-NLR could not predict the pathologic response in response-group 1 (area under the ROC curve [AUC]: 0.45, 95%CI 0.23-0.66) and response-group 2 (AUC: 0.36, 95%CI 0.13-0.59). Nevertheless, it had a poor predictive value in response-group 3 (AUC: 0.55, CI%95 0.33-0.75) with an optimal NLR cutoff value of 2.94. Conclusions: Pre-NLR could not predict the pathological response to neoCRT in our cohort of patients with LARC.     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Diagnosis of hypertension: Ambulatory pediatric American Heart Association/European Society of Hypertension versus blood pressure load thresholds

The agreement between the traditionally‐used ambulatory blood pressure (ABP)‐load thresholds in children and recently‐recommended pediatric American Heart Association (AHA)/European Society of Hypertension (ESH) ABP thresholds for diagnosing ambulatory hypertension (AH), white coat hypertension (WCH), and masked hypertension (MH) has not been evaluated. In this cross‐sectional study on 450 outpatient participants, the authors evaluated the agreement between previously used ABP‐load 25%, 30%, 40%, 50% thresholds and the AHA/ESH thresholds for diagnosing AH, WCH, and MH. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. The AHA threshold diagnosed ambulatory normotension/hypertension closest to ABP load 50% in 88% (95% CI 0.79, 0.96) participants (k 0.67, 95% CI 0.59, 0.75) and the ESH threshold diagnosed ambulatory normotension/hypertension closest to ABP load 40% in 86% (95% CI 0.77, 0.94) participants (k 0.66, 95% CI 0.59, 0.74). In contrast, the AHA/ESH thresholds had a relatively weaker agreement with ABP load 25%/30%. Therefore, the diagnosis of AH was closest between the AHA threshold and ABP load 50% (difference 3%, 95% CI ‐2.6%, 8.6%, p = .29) and between the ESH threshold and ABP load 40% (difference 4%, 95% CI ‐2.1%, 10.1%, p = .19) than between the AHA/ESH and ABP load 25%/30% thresholds. A similar agreement pattern persisted between the AHA/ESH and various ABP load thresholds for diagnosing WCH and MH. The AHA and ESH thresholds diagnosed AH, WCH, and MH closest to ABP load 40%/50% than ABP load 25%/30%. Future outcome‐based studies are needed to guide the optimal use of these ABP thresholds in clinical practice.     

Trichophyton mentagrophytes and T interdigitale genotypes are associated with particular geographic areas and clinical manifestations

The fungi Trichophyton mentagrophytes and T interdigitale account for significant amount of dermatophytosis cases worldwide. These two dermatophytes form a species complex and have a number of ribosomal internal transcribed spacer (ITS) region genotypes, allowing simultaneous species identification and strain typing. Our aim was to describe the geographic distribution of T mentagrophytes/T interdigitale ITS region genotypes and find an association between the genotypes and clinical presentations of respective infections. We performed rDNA ITS region sequencing in 397 Iranian T mentagrophytes/T interdigitale isolates and analysed all available in GenBank entries with sequences of this kind. For the study, 515 clinical annotations were available. Statistical analysis was performed by chi‐squared test and Spearman rank correlation analysis. A total of 971 sequences belonged to genotypes with at least 10 geographic annotations and were classified on the basis of exclusive occurrence in a particular region or high relative contribution to a regional sample. We discerned Asian and Oceanian (“ KU496915 ” Type V, “ KT192500 ” Type VIII, “ KU315316 ”), European (“ FM986750 ” Type III, “ MF926358 ” Type III*, “ KT285210 ” Type VI) and cosmopolitan (“ FM986691 ” Type I, “ JX122216 ” Type II, “ KP132819 ” Type II* and “ AF170453 ” Type XXIV) genotypes. There was statistically significant difference in the ITS genotype distribution between different affected body sites. Trichophyton mentagrophytes “ KT192500 ” Type VIII correlated with tinea cruris, T mentagrophytes “ KU496915 ” Type V correlated with tinea corporis, T interdigitale “ JX122216 ” Type II correlated with tinea pedis and onychomycosis. Trichophyton mentagrophytes and T interdigitale genotypes can be associated with distinct geographic locations and particular clinical presentations.     

Pseudolymphoma (reactive lymphoid hyperplasia) of the liver:A clinical challenge

Reactive lymphoid hyperplasia(RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision.     

Riluzole prevents morphine-induced apoptosis in rat cerebral cortex

Neuronal apoptosis has been shown to be associated with the development of tolerance to morphine. In the present study, we investigated the effect of intracerebroventricular (icv) administration of an inhibitor of glutamate release, riluzole, on morphine-induced apoptosis in the rat cerebral cortex. Various groups of rats received either morphine (intraperitoneally, ip) and vehicle (icv) or morphine (ip) and different doses of riluzole (icv) once per day for 8 days. An in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method was used as an apoptosis assay. Levels of the anti-apoptotic factors Bcl-2 and HSP70 and the pro-apoptotic agent caspase-3 were evaluated by immunoblotting. The glutamate concentration in the cerebral cortex was measured by high performance liquid chromatography (HPLC). The results showed that icv administration of riluzole decreased the number of apoptotic cells in the cerebral cortex compared with the control group, which was treated with morphine (ip) and 1% Tween 80 in 0.9% normal saline (icv). The levels of the anti-apoptotic proteins Bcl-2 and HSP70 were higher in the riluzole groups than in the control. Furthermore, co-administration of riluzole with morphine significantly decreased caspase-3 protein levels and glutamate content of the cerebral cortex compared with the control. In conclusion, we found that icv administration of riluzole attenuates morphine-induced apoptosis in the cerebral cortex after the development of morphine tolerance.     

Comparison of drain clamp after bilateral total knee arthroplasty

Suction drains provide an easy and feasible method for controlling hemorrhage after total knee arthroplasty. However, there has been no compromise regarding the optimum clamping time for these drains. We conducted a randomized clinical trial in 50 patients to compare 12-hour drain clamping and continuous drainage after total knee arthroplasty in terms of wound complications, blood loss, and articular arc of motion. To eliminate any other factor except duration of clamping, we chose to compare only knees belonging to a single patient and to restrict the study to those knees undergoing surgery due to osteoarthritis. From a total of 100 knees (50 patients) studied, the 12-hour-clamping method resulted in a significantly smaller amount of postoperative blood loss (p < 0.001). The passive ranges of motion and wound complications were not significantly different between the two groups.     

Prediction of wound healing in human diabetic foot ulcers by diffuse near‐infrared spectroscopy: A pilot study

A human study was conducted in which the efficacy of in vivo diffuse near‐infrared (NIR) spectroscopy was demonstrated in predicting wound healing in diabetic foot ulcers. Sixteen chronic diabetic wounds were followed and assessed for subsurface oxy‐hemoglobin concentration using the NIR device. Weekly measurements were conducted until there was wound closure, limb amputation, or 20 completed visits without healing. Digital photography measured wound size, and the degree of wound contraction was compared with the NIR results. In the 16 patients followed, seven wounds healed, six limbs were amputated, and three wounds remained opened after 20 visits. The initial values in subsurface hemoglobin concentration in all wounds were higher than the nonwound control sites. Healed wounds showed a consistent reduction of hemoglobin concentration several weeks before closure that approached control site values. In wounds that did not heal or resulted in amputation of the limb, the hemoglobin concentration remained elevated. In some cases, these nonhealing wounds appeared to be improving clinically. A negative slope for the rate of change of hemoglobin concentration was indicative of healing across all wounds. In conclusion, evaluation of wounds using NIR may provide an effective measurement of wound healing. NIR spectroscopy can determine wound healing earlier than that visibly assessed by current clinical approaches.