BHS guidelines on the management of relapsed and refractory diffuse large B-cell lymphoma: Part 1

peer reviewedApproximately 30-40% of patients with diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), will relapse or are unable to obtain a complete remission (CR) after frontline treatment. These patients have a poor prognosis and represent a therapeutic challenge. In this article, we reviewed the recent literature to update the practice guidelines of the Belgian Hematology Society (BHS) Lymphoproliferative Disease Committee for the treatment of relapsed or refractory (R/R) DLBCL. In the first part, we will focus on first relapse and the role of CAR T-cell therapy in first and second relapse. In the second part, we will focus on novel treatment options for patients with a second or higher relapse, secondary central nervous system (CNS) relapse and high-grade lymphoma

BHS GUIDELINES ON THE MANAGEMENT OF RELAPSED AND REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: PART 2

peer reviewedApproximately 30-40% of patients with diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), will relapse or are unable to obtain a complete remission (CR) after frontline treatment. These patients have a poor prognosis and represent a therapeutic challenge. In this article, we reviewed the recent literature to update the practice guidelines of the Belgian Hematology Society (BHS) Lymphoproliferative Disease Committee for the treatment of relapsed or refractory (R/R) DLBCL. In the first part, we will focus on first relapse and the role of CAR T-cell therapy in first and second relapse. In the second part, we will focus on novel treatment options for patients with a second or higher relapse, secondary central nervous system (CNS) relapse and high-grade lymphoma

Spontaneous bladder rupture diagnosis based on urinary appearance of mesothelial cells: a case report

Introduction. Spontaneous bladder rupture is an extremely rare clinical event that is associated with urinary ascites and apparent acute renal failure. This event is difficult to diagnose clinically, even with advanced techniques such as computed tomography; however, the timely diagnosis of this condition is critical. Here, we report a case of a patient who experienced a spontaneous intraperitoneal bladder rupture 10 years after postoperative pelvic irradiation for the treatment of uterine cancer. In this report of a rare case, we describe the contribution of the appearance of mesothelial cells in the urine to the diagnosis of this condition. Case presentation. Our patient was a 71-year-old Asian woman who experienced lower abdominal pain and vomiting of two days duration. On admission, abdominal computed tomography showed intraperitoneal fluid collection and her blood tests revealed acute renal failure and hyperkalemia. She underwent hemodialysis and a transurethral catheter was inserted. The transurethral catheter was removed three days after her admission. Four days after the catheter removal, her symptoms recurred and her serum creatinine and blood urea nitrogen levels were elevated. We noted the presence of mesothelial cells in her urine, which led to a diagnosis of intraperitoneal bladder rupture. She underwent surgical repair of her bladder and hyperbaric oxygen therapy, and was discharged after her renal function returned to normal. Conclusion: Urine analysis is a simple and non-invasive test and we believe that a thorough urine analysis may contribute to the early diagnosis of an intraperitoneal bladder rupture. We think that the findings presented in this case report will significantly enhance our understanding of the etiology of bladder rupture. Moreover, these case findings may help nephrologists and urologists to rapidly diagnose this condition

Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.</p> <p>Methods</p> <p>review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1^stSeptember, 2006 and 31^stJuly, 2007.</p> <p>Results</p> <p>179 episodes of either primary (<it>n </it>= 117) or secondary (<it>n </it>= 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; <it>p </it>< 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; <it>p </it>= 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (<it>n </it>= 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; <it>p </it>< 0.050).</p> <p>Conclusion</p> <p>In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.</p

Implementation of a program for type 2 diabetes based on the Chronic Care Model in a hospital-centered health care system: "the Belgian experience"

Background: Most research publications on Chronic Care Model (CCM) implementation originate from organizations or countries with a well-structured primary health care system. Information about efforts made in countries with a less well-organized primary health care system is scarce. In 2003, the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting, a setting where the organisational framework for chronic care is mainly hospital-centered. Methods: Process evaluation of an action research project (2003-2007) guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients. In consultation with the region a program for type 2 diabetes patients was developed. The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey (ACIC). A multimethod approach was used to evaluate the implementation process. The resulting data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process. Results: The overall ACIC score improved from 1.45 (limited support) at the start of the study to 5.5 (basic support) at the end of the study. The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care. The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator. Important barriers were the complexity of the intervention, the lack of quality data, inadequate information technology support, the lack of commitment procedures and the uncertainty about sustainable funding. Conclusion: Guided by the CCM, this study highlights the opportunities and the bottlenecks for adapting chronic care delivery in a primary care system with limited structure. The study succeeded in achieving a considerable improvement of the overall support for diabetes patients but further improvement requires a shift towards system thinking among policy makers. Currently primary care providers lack the opportunities to take up full responsibility for chronic care

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60&nbsp;years old