Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Indwelling time of peripherally inserted central catheters and incidence of bloodstream infections in haematology patients: a cohort study.

BACKGROUND: We aimed to assess whether longer indwelling time of peripherally inserted central catheters (PICC) increases risk of central line associated bloodstream infections (CLABSI) in haematology patients. METHODS: Multicentre retrospective cohort study among haematology patients receiving PICCs between 2013 and 2015. Occurrence of CLABSI based on CDC definitions was assessed. We calculated incidence rates, determined risk factors for CLABSI and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. We compared diagnoses and treatment characteristics between 2013-2015 and 2015-2020. RESULTS: 455 PICCs placed in 370 patients were included, comprising 19,063 catheter days. Median indwelling time was 26 days (range 0-385) and CLABSI incidence was 4.0 per 1000 catheter days, with a median time to CLABSI of 33 days (range 18-158). Aplastic anaemia (AA) was associated with an increased risk of CLABSI; patients undergoing autologous stem cell transplantation (SCT) were less likely to develop CLABSI. In the unadjusted analysis, PICCs with an indwelling time of 15-28 days, 29-42 days, 43-56 days and > 56 days each had an increased CLABSI incidence rate ratio of 2.4 (1.2-4.8), 2.2 (0.95-5.0), 3.4 (1.6-7.5) and 1.7 (0.9-3.5), respectively, compared to PICCs in place for < 15 days. However, after adjusting for AA and SCT, there was no significant difference in incidence rates between dwell times (p 0.067). CONCLUSIONS: Our study shows that risk of CLABSI does not appear to increase with longer PICC indwelling time. Routine replacement of PICCs therefore is unlikely to prevent CLABSI in this population.

A real or apparent decrease in glomerular filtration rate in patients using olaparib?

PURPOSE: Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for ovarian and metastatic breast cancer. Increased serum creatinine levels have been observed in patients taking olaparib, but the underlying mechanism is unknown. This study aimed to investigate if patients receiving olaparib have increased creatinine levels during olaparib treatment and whether this actually relates to a declined glomerular filtration rate (GFR). METHODS: We retrospectively identified patients using olaparib at the Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL) from 2012 until 2020. Patients with at least one plasma or serum sample available at baseline/off treatment and during olaparib treatment were included. Cystatin C levels were measured, creatinine levels were available and renal function was determined by calculating the estimated glomerular filtration rate (eGFR) using the Creatinine Equation (CKD-EPI 2009) and the Cystatin C Equation (CKD-EPI 2012). RESULTS: In total, 66 patients were included. Olaparib treatment was associated with a 14% increase in median creatinine from 72 (inter quartile range (IQR): 22) µmol/L before/off treatment to 82 (IQR: 20) µmol/L during treatment (p < 0.001) and a 13% decrease in median creatinine-derived eGFR from 86 (IQR: 26) mL/min/1.73 m2 before/off treatment to 75 (IQR: 29) mL/min/1.73 m2 during treatment (p < 0.001). Olaparib treatment had no significant effect on median cystatin C levels (p = 0.520) and the median cystatin C-derived eGFR (p = 0.918). CONCLUSIONS: This study demonstrates that olaparib likely causes inhibition of renal transporters leading to a reversible and dose-dependent increase in creatinine and does not affect GFR, since the median cystatin C-derived eGFR was comparable before/off treatment and during treatment of olaparib. Using the creatinine-derived eGFR can give an underestimation of GFR in patients taking olaparib. Therefore, an alternative renal marker such as cystatin C should be used to accurately calculate eGFR in patients taking olaparib.

C-reactive protein kinetics and its predictive value in orthopedic (trauma) surgery: A systematic review.

In Orthopedic Trauma Surgery (OTS), C-reactive- protein (CRP) is a widely used marker for the diagnosis of postoperative wound infections (POWI's) and other complications. The aim of this systematic review was to describe specific CRP kinetics and to evaluate the diagnostic value of CRP for te detection of post-operative complications in OTS. The same pattern is reported consistently, where the highest levels of CRP are found at post-operative-day two or three, returning to normal in three weeks. Amplitude varies per procedure. Persistently high CRP levels or secondary increases may indicate complications. A low CRP may be used to rule out complications.

[Multidisciplinary approach of facial injuries]. / Multidisciplinaire aanpak bij aangezichtsletsel.

BACKGROUND: Approximately one quarter of polytrauma patients has facial injuries, which usually lead to loss of form and function. Several specialties are involved in the acute and reconstructive phases of facial injuries, such as oral and maxillofacial surgery, otorhinolaryngology, plastic surgery, ophthalmology and dentistry. CASE DESCRIPTION: A 25-year-old man with severe facial injuries was brought to the shock room after sustaining high-energy trauma. He had a panfacial fracture that required reconstruction. This was done with two surgeries, with an interval of 4 days. The patient recovered successfully after this. CONCLUSION: Because of the complexity of facial trauma, many factors are involved in acute care and treatment. It is therefore important to designate one coordinating specialty to guide this process. The oral and maxillofacial surgeon plays a vital role in this.

Survival of autoreactive T lymphocytes by microRNA-mediated regulation of apoptosis through TRAIL and Fas in type 1 diabetes.

Autoreactive CD8(+) T cells recognizing autoantigens expressed by pancreatic islets lead to the destruction of insulin-producing beta cells in type 1 diabetes (T1D), but these T cells also occur in healthy subjects. We tested the hypothesis that uncontrolled expansion of diabetogenic T cells in patients occurs, resulting from failure to activate apoptosis. We compared function, transcriptome and epigenetic regulation thereof in relation with fate upon repeated exposure to islet-autoantigen of islet autoreactive T cells from healthy and type 1 diabetic donors with identical islet epitope specificity and HLA-A2 restriction. Patient's T cells proliferated exponentially, whereas those of non-diabetic origin succumbed to cell death. Transcriptome analysis revealed reduced expression of TRAIL, TRAIL-R2, FAS and FASLG (members of the extrinsic apoptosis pathway) in patient-derived compared with healthy donor-derived T cells. This was mirrored by increased expression of microRNAs predicted to regulate these particular genes, namely miR-98, miR-23b and miR-590-5p. Gene-specific targeting by these microRNAs was confirmed using dual-luciferase reporter assays. Finally, transfection of these microRNAs into primary T cells reduced FAS and TRAIL mRNA underscoring their functional relevance. We propose that repression of pro-apoptotic pathways by microRNAs contributes to unrestricted expansion of diabetogenic cytotoxic T cells, implicating microRNA-mediated gene silencing in islet autoimmunity in T1D.

[Splenectomy in a large general hospital: often caused by iatrogenic injury, often causing multiple complications; poor adherence to post-operative guidelines for vaccination and prophylaxis]. / Splenectomie in een groot algemeen ziekenhuis: vaak iatrogeen letsel als oorzaak, veel complicaties tot gevolg; naleving postoperatieve richtlijnen voor vaccinatie en profylaxe gebrekkig.

OBJECTIVE: To assess the indications, complications and mortality associated with splenectomy in a large general hospital, and to evaluate adherence to guidelines for postoperative vaccination and prophylactic antibiotics. DESIGN: Retrospective, descriptive. METHOD: Data were collected on 106 patients who underwent splenectomy between 1999 and 2004. Indications for surgery, complications, duration of hospitalisation, and vaccination status were investigated retrospectively. Patients were contacted by telephone for a structured interview regarding vaccination and antibiotic prophylaxis. RESULTS: Of the 95 patients with sufficient data for analysis, 41 underwent elective surgery and 54 underwent non-elective surgery, including 37 who required splenectomy due to iatrogenic injury. Posteroperative complications arose in 45 patients, including 23 who developed serious complications. 10 patients died due to complications, including 7 who died within one month after the procedure. Vaccination coverage for the entire group was 58%. CONCLUSION: In this large general hospital, splenectomy was often performed due to iatrogenic injury and was associated with a relatively high complication rate. Adherence to guidelines on vaccination and prophylactic antibiotics could be improved.

[Diagnostic image (212). A man with severe abdominal pain]. / Diagnose in beeld (212). Een man met heftige buikpijn.

A 36-year-old man presented with acute abdominal pain due to occlusion of the superior mesenteric artery associated with intestinal rotation caused by an upper abdominal postoperative adhesion.

Induction of c-Jun immunoreactivity in spinal cord and brainstem neurons in a transgenic mouse model for amyotrophic lateral sclerosis.

Transgenic mice carrying amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutations develop a motoneuron disease resembling human ALS. c-Jun is a transcription factor frequently induced in injured neurons. In this study we have examined the distribution of c-Jun-immunoreactivity in the brainstem and spinal cord of transgenic SOD1 mice with a glycine 93 alanine (G93A) mutation. In non-transgenic littermates c-Jun immunostaining was predominantly situated in motoneurons. The number of c-Jun immunoreactive motoneuron was reduced in SOD1(G93A) mice due to pronounced loss of motoneurons. In SOD1(G93A) mice, however, c-Jun-immunoreactivity was strongly induced in neurons in the intermediate zone (Rexed's laminae V-VIII and X) of the spinal cord and throughout the brainstem reticular formation. These findings are of interest since increased levels of c-jun also have been found in the intermediate zone of the spinal cord of ALS patients. This c-Jun may be involved in the neurodegenerative processes both in ALS and in motoneuron disease in SOD1(G93A) mice.

Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis.

Using immunohistochemical techniques, we analyzed iris biopsy specimens from eight patients with Fuchs' heterochromic cyclitis, seven patients with various other types of uveitis, and eight glaucoma patients without uveitis. No specific abnormalities related to Fuchs' heterochromic cyclitis could be detected. Four of the patients with Fuchs' heterochromic cyclitis and four of the patients with uveitis showed evidence of an inflammatory cell infiltrate, which was a mixture of interleukin-2 receptor-negative T helper and suppressor cells, B lymphocytes, and plasma cells. Only an occasional T lymphocyte could be seen in two of the patients without uveitis. The class II antigen HLA-DR was expressed on iris stromal cells in every patient in the Fuchs' heterochromic cyclitis group and uveitis group and in six of the patients in the nonuveitis group. In six of the Fuchs' heterochromic cyclitis patients, including two without immunohistochemical evidence of inflammatory cell infiltrate, histologic abnormalities were present on hematoxylin and eosin sections.

Sarcoplasmic masses. Enzyme histochemistry and autoradiography.

A comparative enzyme-histochemical study was made of the sarcoplasmic masses in a muscle biopsy specimen from a patient with myotonic dystrophy and those in the jaw-muscle of the Rana temporaria tadpole. The enzyme-histochemical patterns of the two methods proved to be identical. An autoradiographic study was made of the sarcoplasmic masses in the R temporaria tadpole with DL-thyroxine-2-14C and levomethionine 35S. The radioactivity labeled compounds were found to be stored or incorporated mainly in the myofibrillae, and virtually not at all in the sarcoplasmic masses.