Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort ...made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (>10 mut/Mb) was associated with high PD-L1 expression (TPS 50–100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.
The inside front cover image is based on the Original Article Ventricular activation pattern assessment during right ventricular pacing: Ultra‐high‐frequency ECG study by Karol Curila et al., ...https://doi.org/10.1111/jce.14985.
Penile squamous cell carcinoma (pSCC) is a rare malignancy with a slowly increasing incidence and variable prognosis. Regional lymph node involvement signifies poor prognosis but represents a late ...sign, and more prognostic markers for effective patient risk stratification are urgently needed. In this retrospective study, 152 tumour samples with formalin-fixed, paraffin-embedded tissue were analysed for traditional pathological variables, tumour budding, p53, p16, and mismatch repair proteins (MMR) immunohistochemistry. The density of tumour lymphocytic infiltrate was also determined, using subjective evaluation by two pathologists (brisk/non-brisk/absent) and also using the immunoscore method, which categorised the cohort into five immunoscore groups according to the number of CD3+ and CD8+ T-cells in both the tumour centre and tumour invasion front. Only one case (0.6%) was MMR-deficient. Tumour budding count ≥5 tumour buds/20× power field and non-brisk/absent lymphocytic infiltrate were significant negative predictors of both the overall survival (OS) and cancer-specific survival (CSS), whereas a low immunoscore was a significant marker of shorter OS but not CSS. Advanced pT stage (3+4) was a significant marker of shorter CSS but not OS. In the multivariate analysis, high-grade budding was a significant parameter if adjusted for the patient's age and associated variables, except for the pN stage. The lymphocytic infiltrate retained its prognostic significance if adjusted for age and associated variables. The negative prognostic significance of the previously described parameters (lymphatic, venous, and perineural invasion, regional lymph node metastasis, and p53 mutated profile) were confirmed in our study. Grade, histological subtype, and HPV status (as determined by p16 immunohistochemistry) showed, surprisingly, little or no prognostic significance.
The effect of left ventricular septal myocardial pacing (LVSP) and left bundle branch pacing (LBBP) on ventricular synchrony and left ventricular (LV) hemodynamic status is poorly understood.
The aim ...of this study was to investigate the impact of LVSP and LBBP vs biventricular pacing (BVP) on ventricular electrical synchrony and hemodynamic status in cardiac resynchronization therapy patients.
In cardiac resynchronization therapy candidates with LV conduction disease, ventricular synchrony was assessed by measuring QRS duration (QRSd) and using ultra-high-frequency electrocardiography. LV electrical dyssynchrony was assessed as the difference between the first activation in leads V1 to V8 to the last from leads V4 to V8. LV hemodynamic status was estimated using invasive systolic blood pressure measurement during multiple transitions between LBBP, LVSP, and BVP.
A total of 35 patients with a mean LV ejection fraction of 29% and a mean QRSd of 168 ± 24 ms were included. Thirteen had ischemic cardiomyopathy. QRSd during BVP, LVSP, and LBBP was the same, but LBBP provided shorter LV electrical dyssynchrony than BVP (−10 ms; 95% CI: −16 to −4 ms; P = 0.001); the difference between LVSP and BVP was not significant (−5 ms; 95% CI: −12 to 1 ms; P = 0.10). LBBP was associated with higher systolic blood pressure than BVP (4%; 95% CI: 2%-5%; P < 0.001), whereas LVSP was not (1%; 95% CI: 0%-2%; P = 0.10). Hemodynamic differences during LBBP and LVSP vs BVP were more pronounced in nonischemic than ischemic patients.
Ultra-high-frequency electrocardiography allowed the documentation of differences in LV synchrony between LBBP, LVSP, and BVP, which were not observed by measuring QRSd. LVSP provided the same LV synchrony and hemodynamic status as BVP, while LBBP was better than BVP in both.
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The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer.
We ...evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative diagnostic biopsy and postoperative definitive histology. The data were statistically processed.
Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative biopsy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/intermediate-risk group to intermediate-high/high-risk disease group.
Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from diagnostic biopsies made in referring hospitals. Sentinel lymph node biopsy should be performed even in clinically low/intermediate-risk disease group.
Despite high success rate of DREZ lesioning in the treatment of intractable central pain, there is still a significant incidence of patients without satisfactory post-operative effect. The aim of the ...study was to evaluate the long-term effect of DREZ lesioning using both a subjective assessment using a visual analog scale (VAS) to quantify residual pain and an assessment using the screening tool (painDETECT Questionnaire, PD-Q).
DREZ lesioning was performed in 52 patients from a total 441 cases with brachial plexus injury (11.8%) during a 17-year period (1995-2011). The effect of surgery was retrospectively assessed in 48 patients.
A decrease in pre-operative pain by more than 75% (Group I) was achieved in 70.8% of patients and another 20.8% reported significant improvement (Group II). The surgery was unsucessful in 8.4% (Group III). We found a significant correlation between 'improvement' groups from both methods of assessments. Patients from Group I usually complained of residual nociceptive pain according to PD-Q, patients from Group II typically had pain of unclear origin, and all cases those in Group III suffered from neuropathic pain, Cramer's V = .66, P < .001. Overall, 66.7% of patients had resolved neuropathic pain, 20.8% patients had more serious complaints and may also suffer from residual neuropathic pain, while 12.5% had unresolved neuropathic pain.
DREZ lesioning is a safe and effective method with success rates of about 90%. PD-Q scores correspond to subjective satisfaction with the surgery and it seems to be a suitable screening tool for finding patients with residual neuropathic pain after surgery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Functional electrical stimulation–assisted cycle ergometry (FESCE) can deliver active exercise to critically ill patients, including those who are sedated. Aerobic exercise is known to ...stimulate skeletal muscle glucose uptake. We asked whether FESCE can reduce intravenous insulin requirements and improve insulin sensitivity in intensive care unit (ICU) patients.
Method
We performed an a priori–planned secondary analysis of data from an outcome‐based randomized controlled trial (NCT 02864745) of FESCE‐based early‐mobility program vs standard of care in mechanically ventilated patients. We analyzed glucose profile, glucose intake, and insulin requirements during ICU stay in all enrolled patients. In a nested subgroup, we performed hyperinsulinemic (120 mIU/min/m2) euglycemic clamps at days 0, 7, and 180 (n = 30, 23, and 11, respectively).
Results
We randomized 150 patients 1:1 to receive intervention or standard of care. Seventeen (23%) patients in each study arm had a history of diabetes. During ICU stay, patients received 137 ± 65 and 137 ± 88 g/day carbohydrate (P = .97), and 31 vs 35 (P = .62) of them required insulin infusion to maintain blood glucose 8.61 ± 2.82 vs 8.73 ± 2.67 mM (P = .75, n = 11,254). In those treated with insulin, median daily dose was 53 IU (interquartile range IQR, 25–95) vs 62 IU (IQR, 26–96) in the intervention and control arm, respectively (P = .44). In the subgroup of patients undergoing hyperglycemic clamps, insulin sensitivities improved similarly and significantly from acute and protracted critical illness to 6 months after discharge.
Conclusion
The FESCE‐based early‐mobility program does not significantly reduce insulin requirements in critically ill patients on mechanical ventilation.
OBJECTIVES:The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month ...data.
METHODS:A total of 106 patients with true resistant hypertension were enrolled in this study52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients.
RESULTS:Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001).
CONCLUSION:In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.
Purpose: The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and ...central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics.
Materials and methods: A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests.
Results: Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points; p = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5-17.5, p = .004) and mental component summary score (9.5 points; 95%CI 1.9-17.1, p = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6-14.0; p = .033), bodily pain (8.7 points; 95%CI 1.6-17.6; p = .018), and social functioning (8.2 points; 95%CI 3.0-17.4; p = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all p > .05).
Conclusion: Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. ...However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA).
Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month HR 3.6 (95% CI 1.03; 12.5), P = 0.045; however, it did not reach statistical significance at 1 year HR 1.9 (95% CI 0.8; 4.4), P = 0.138.
Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m².
ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.
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