Assessment of fitness for open repair in patients with infrarenal abdominal aortic aneurysms.

OBJECTIVE: Endovascular aortic repair (EVAR) was originally designed as a treatment modality for patients with abdominal aortic aneurysms (AAAs) deemed unfit for open repair. However, the definition of "unfit for open repair" is largely subjective and heterogenous. The purpose of this study was to compare patients deemed unfit for open repair who underwent EVAR to a matched cohort who underwent open repair for infrarenal AAAs. METHODS: The Vascular Quality Initiative of the Society for Vascular Surgery was queried for patients who underwent EVAR and open infrarenal AAA repair from 2003 to 2022. Patients that underwent EVAR were included if they were deemed unfit for open repair by the operating surgeon. EVAR patients deemed unfit because of a hostile abdomen were excluded. Patients in both the open and EVAR datasets were excluded if their repair was deemed non-elective or if they had prior aortic surgery. EVAR patients were matched to a cohort of open patients. The primary outcome for this study was 1-year mortality. Secondary outcomes included 30-day mortality, major adverse cardiac events, pulmonary complications, non-home discharge, reinterventions, and 5-year survival. RESULTS: A total of 5310 EVAR patients were identified who were deemed unfit for open repair. Of those, 3028 EVAR patients (57.0%) were able to be matched 1:1 to a cohort of open patients. Open patients had higher rates of major adverse cardiac events (20.2% vs 4.4%; P < .001), pulmonary complications (12.8% vs 1.6%; P < .001), non-home discharges (28.5% vs 7.9%; P < .001), and 30-day mortality (4.5% vs 1.4%; P < .001). There were no differences in early survival, but open repair had better middle and late survival compared with EVAR over the course of 5 years. A total of 74 EVAR patients (2.4%) had reinterventions during the study period. EVAR patients that required interventions had higher 1-year (40.5% vs 7.3%; P < .001) and 5-year mortality (43.2% vs 14.1%; P < .001) compared with those that did not require reinterventions. EVAR patients who had reinterventions had higher 1-year (40.5% vs 6.3%; P < .001) and 5-year (43.2% vs 20.3%; P = .006) mortality compared with their matched open cohort. CONCLUSIONS: Patients undergoing EVAR for AAAs who are deemed unfit for open repair have better perioperative morbidity and mortality compared with open repair. However, patients who had an open repair had better middle and late survival over the course of 5 years. The categorization of unfitness for open surgery may be inaccurate and re-evaluation of this terminology/concept should be undertaken.

Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant.

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen.

A systematic review of venetoclax for the treatment of unfit AML patients in real-world: is all that glitters gold?

Acute myeloid leukemia (AML) is an aggressive hematological disease that mainly affects elderly patients. Following the randomized VIALE-A trial, current standard treatment in patients who are not candidates for intensive chemotherapy consists of the combination of venetoclax (VEN), a selective inhibitor of the anti-apoptotic protein BCL-2, with azacitidine (AZA) or decitabine (DEC). We performed a systematic review to critically assess the growing existing evidence regarding the effectiveness of the VEN-based combinations in unfit adult patients with newly diagnosed AML in the real-world setting. Following PRISMA guidelines, a systematic search of published manuscripts and conference abstracts (European Hematology Association and American Society of Hematology) was conducted (updated March 2024). Primary outcomes were composite complete remission (CRc) and median overall survival (mOS). A total of 73 studies fulfilled inclusion criteria, with a median age of 73 years old. The weighted mean mOS was 10.3 months among 7 138 patients, significantly lower than expected according to the VIALE-A trial (14.7 months), while the weighted mean CRc rate was 58.2% among 5 831 patients, slightly lower to that reported in the VIALE-A (66.4%). Early death rates at 30 and 60 days were 5% and 13%, respectively. The weighted mean percentage of subsequent allogeneic transplant was 15.4%. In conclusion, breakthrough mOS reported in the VIALE-A trial using VEN-AZA was not well reproduced in real world for unfit newly diagnosed AML patients, while CRc rates were more consistent. Strategies to optimize patient selection, dosing regimens, and supportive care are crucial to improve outcomes in real-world.

Tamsulosin 0.8 mg daily dose in management of BPH patients with failed tamsulosin 0.4 mg monotherapy and unfit for surgical intervention.

AIM: This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention. MATERIALS AND METHODS: Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment. RESULTS: All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively. CONCLUSION: Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

Use of gemcitabine, oxaliplatin, and anti-CD20 therapy in children and adolescents with non-Hodgkin lymphoma unfit for intensive therapy.

Multiagent immunochemotherapy affords excellent outcomes in pediatric non-Hodgkin lymphoma (NHL); however, scarce data exist for patients unfit for intensive treatment. Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is well tolerated and efficacious in elderly adults with NHL; however, its use has not been described in pediatrics. In this retrospective, single-center study, six children with mature B-cell NHL and significant comorbidities received anti-CD20 therapy with GemOx (rituximab or obinutuzumab or ofatumumab with gemcitabine and oxaliplatin [R/O-GemOx]). R/O-GemOx was well tolerated and resulted in complete response in two of three patients with newly diagnosed NHL and one of three patients with primary refractory NHL. R/O-GemOx is a viable treatment option for children with NHL who cannot tolerate intensive therapy.

An Update on FLT3 in Acute Myeloid Leukemia: Pathophysiology and Therapeutic Landscape.

PURPOSE OF REVIEW: This review aims to summarize the pathophysiology, clinical presentation, and management of acute myeloid leukemia (AML) with FMS-like tyrosine kinase-3 (FLT3) mutations. RECENT FINDINGS: The recent European Leukemia Net (ELN2022) recommendations re-classified AML with FLT3 internal tandem duplications (FLT3-ITD) as intermediate risk regardless of Nucleophosmin 1 (NPM1) co-mutation or the FLT3 allelic ratio. Allogeneic hematopoietic cell transplantation (alloHCT) is now recommended for all eligible patients with FLT3-ITD AML. This review outlines the role of FLT3 inhibitors in induction and consolidation, as well as for post-alloHCT maintenance. It outlines the unique challenges and advantages of assessing FLT3 measurable residual disease (MRD) and discusses the pre-clinical basis for the combination of FLT3 and menin inhibitors. And, for the older or unfit patient ineligible for upfront intensive chemotherapy, it discusses the recent clinical trials incorporating FLT3 inhibitors into azacytidine- and venetoclax-based regimens. Finally, it proposes a rational sequential approach for integrating FLT3 inhibitors into less intensive regimens, with a focus on improved tolerability in the older and unfit patient population. The management of AML with FLT3 mutation remains a challenge in clinical practice. This review provides an update on the pathophysiology and therapeutic landscape of FLT3 AML, as well as a clinical management framework for managing the older or unfit patient ineligible for intensive chemotherapy.

Acute Myeloid Leukemia Treatment in the Elderly: A Comprehensive Review of the Present and Future.

BACKGROUND: Acute myeloid leukemia (AML) is a disease of the hematopoietic system that remains a therapeutic challenge despite advances in our understanding of the underlying cancer biology in the past decade. It is also an affliction of the elderly that predominantly affects patients over 60 years of age. Standard therapy involves intensive chemotherapy that is often difficult to tolerate in older populations. Fortunately, recent developments in molecular targeting have shown promising results in treating leukemia, paving the way for novel treatment strategies that are easier to tolerate. SUMMARY: Venetoclax, a BCL-2 inhibitor, when combined with a hypomethylating agent, has proven to be a highly effective and well-tolerated drug and established itself as a new standard for treating AML in patients who are unfit for standard intensive therapy. Other targeted therapies include clinically proven and FDA-approved agents, such as IDH1/2 inhibitors, FLT3 inhibitors, and Gemtuzumab, as well as newer and more experimental drugs such as magrolimab, PI-kinase inhibitors, and T-cell engaging therapy. Some of the novel agents such as magrolimab and menin inhibitors are particularly promising, providing therapeutic options to a wider population of patients than ever before. Determining who will benefit from intense or novel low-intense therapy remains a challenge, and it requires careful assessment of individual patient's fitness and disease characteristics. KEY MESSAGES: This article reviews past and current treatment strategies that harness various mechanisms of leukemia-targeting agents and introduces novel therapies on the horizon aimed at exploring therapeutic options for the elderly and unfit patient population. It also provides a strategy to select the best available therapy for elderly patients with both newly diagnosed and relapsed/refractory AML.

Self-harming behaviors and forensic system-related factors: an analysis of the Ontario review board database.

BACKGROUND: In Canada, ensuring public safety, and the safety and well-being of accused individuals under the jurisdiction of the provincial review board are very important. While previous studies have reported a significant risk of self-harming behaviors (non-suicidal self-injury and suicide attempt) in forensic psychiatric settings, no large population study has assessed any relationship between forensic system-related factors and self-harming behaviors. A better understanding of these factors can help clinicians implement protective measures to mitigate self-harming behaviors or actions. METHODS: Using the Ontario Review Board (ORB) database covering 2014-2015 period (n = 1211, mean age = 42.5 ± 13.37 years, males = 86.1%), we analyzed the prevalence and factors associated with self-harming behaviors, emphasizing the characterization of the forensic system-related factors (ORB status, legal status, type of offense, previous criminal history, and victim relationship). The relationships between the forensic system-related factors and self-harming behaviors were explored using five separate logistic regression models, controlling for clinical and sociodemographic characteristics. RESULTS: Approximately 4% of the individuals in the forensic system over the study period engaged in self-harming behaviors Among the studied patients, individuals determined to be unfit to stand trial and inpatients were significantly more likely to have self-harming behaviors. There was no significant relationship between the type of offence, victim relationship, and previous criminal history with self-harming behavior. CONCLUSION: Forensic psychiatry inpatients should have close observation, screening, monitoring, and individual tailored management strategies for self-harming behaviors. The findings of this study indicate that forensic system-related factors, especially those that pertain to the status of individuals in the forensic system (i.e., unfit to stand trial and being an inpatient) are more responsible for self-harming behaviors among forensic patients in Ontario.

Special considerations to the assessment of fitness to stand trial in Australia.

Australian criminal law presumes that defendants are fit to stand trial until proven otherwise on the balance of probabilities. Forensic mental health experts often provide opinions to the court about defendants' fitness, which requires them to understand the legal context within which the court decides the defendant's fitness status. This article outlines important case law considerations to the assessment of fitness in Australia, including the notions that fitness must be evaluated when there is a 'real and substantial question', assessments should be 'reasonable and common sense' and accommodations should be considered when impairments in capacity are evident. The essentially negligible impact of delusions, an unhelpful defence, unmanageable behaviour and poor defendant-lawyer relationship are also considered. Finally, precedent is reviewed for the use of the Presser standards in New Zealand and other pacific jurisdictions.

Understanding who benefits from endovascular aortic repair in those deemed unfit for open repair.

INTRODUCTION: Patients with abdominal aortic aneurysms (AAAs) who are deemed unacceptable candidates for open repair (UNFIT) pose a clinical challenge. The EVAR2 Trial randomized UNFIT patients to endovascular aortic repair (EVAR) vs no intervention from 1999 to 2003, concluding that survival was not improved by EVAR. However, outcomes after EVAR over the last 2 decades have dramatically changed. Thus, the purpose of this study was to evaluate outcomes after EVAR in UNFIT patients using more contemporary data and to determine which subsets of UNFIT patients may potentially benefit from EVAR. METHODS: The Vascular Quality Initiative database (2003-2020) was used to identify elective EVARs for AAAs. Patients were categorized as UNFIT or suitable (SUITABLE) for open repair by the operative surgeon. Predicted 1-year mortality of untreated AAAs was calculated via a modified Gagne Index adjusted for AAA size. The primary outcome for the study was 30-day mortality. Secondary outcomes included perioperative major adverse cardiac events (a composite of clinically significant arrhythmia, congestive heart failure, and myocardial infarction), length of stay, and 1-year mortality. RESULTS: A total of 31,471 patients met study criteria with 27,036 (85.9%) deemed SUITABLE and 4435 (14.1%) UNFIT. UNFIT patients were more likely to experience a perioperative major adverse cardiac event (5.1% vs 2.2%, P < .001) and had longer lengths of stay (1 day [interquartile range, 1-3 days] vs 1 day [interquartile range, 1-2 days], P < .001). The 30-day mortality was significantly higher for UNFIT patients (0.8% vs 0.4%, P < .001). UNFIT patients had worse 1-year survival compared with SUITABLE patients. However, UNFIT and SUITABLE patients had significantly improved actual 1-year mortality with EVAR compared with predicted 1-year mortality without EVAR: 9.5% vs 15.6% (P < .001) and 4.0% vs 11.7% (P < .001), respectively. The mortality benefit after EVAR in UNFIT patients was primarily restricted to those with smaller Gagne Indices and larger aneurysm diameters. Patients deemed unsuitable for open repair due to frailty or multiple reasons had significantly higher 30-day mortality rates after EVAR when compared with SUITABLE patients (1.3% vs 1.6% vs 0.4%, P < .001). Those deemed unsuitable for open repair due to frailty or multiple reasons had worse 1-year cumulative survival compared with all other UNFIT patients. CONCLUSIONS: Despite being high risk with higher perioperative morbidity and mortality, UNFIT patients have lower actual 1-year mortality with EVAR than predicted 1-year mortality without EVAR. However, this potential benefit is reserved to those with small Gagne Indices, larger AAA diameters, and lack of frailty.

Efficacy of non-intensive therapies approved for relapsed/refractory acute myeloid leukemia: a systematic literature review.

Aim: De novo relapsed and/or refractory acute myeloid leukemia (rrAML) has limited treatment options for patients not eligible ('unfit') to receive intensive chemotherapy-based interventions. The authors aimed to summarize outcomes for licensed therapies in this setting. Materials & methods: A systematic literature review identified licensed therapies in this setting. A feasibility assessment was made to conduct a network meta-analysis to evaluate comparative efficacy. Results: Seven unique trials were identified. Median survival months were 13.8 for gemtuzumab ozogamicin (GO), 9.3 for gilteritinib (FLT3 mutated rrAML), 5.6 for low-dose cytarabine and 3.2 for best supportive care; transplant rates with gilteritinib and GO were 25.5 and 19%, respectively. A network meta-analysis was not feasible. Conclusion: There remains a high unmet need in de novo rrAML patients not eligible for intensive therapy, with GO and gilteritinib (only FLT3-mutated AML) providing the best current options.

Some patients with acute myeloid leukemia (AML) have no response to initial treatment or have a response that is subsequently lost. Follow-on treatment options after that initial stage are limited, especially for patients who are not able to have intensive therapy, such as chemotherapy, due to age, physical or cognitive function, existing comorbidities or symptoms. This study aimed to review the published literature to identify data associated with treatments that are licensed for use in patients ineligible for intensive therapy who do not maintain a response from their initial therapy. The study found that the drug gilteritinib was an option for the subgroup of AML patients with FLT3-mutated disease with an average life expectancy just under 1 year, while gemtuzumab ozogamicin was an option for a wider group of AML patients with a life expectancy just over 1 year. Between a fifth and a quarter of patients went on to receive a stem-cell transplant after treatment with one of these. With limited options, this patient group needs further attention; however, the availability of the previously mentioned treatments is promising.

The Ontario Forensic Mental Health System: A Population-based Review.

OBJECTIVE: The purpose of this study was to increase the understanding of the Canadian forensic psychiatry system by providing a population-based overview of the Ontario forensic mental health system. METHODS: Data were collected on 1,240 accused adults who were subject to the jurisdiction of the Ontario Review Board (ORB) between 2014 and 2015. Archival data were retrieved from annual ORB hearing hospital reports for accused supervised by all nine adult forensic psychiatry facilities across Ontario. RESULTS: The sample included not criminally responsible (NCR; 91.6%) and unfit to stand trial (UST; 8.4%) accused. The majority of the sample was male (85.7%), single (70.1%), unemployed (63.6%), with a high school education (48.8%). Most were on a detention order (78.5%) and almost half were living in the community at the time of the report (48.8%). The majority had prior contact with psychiatric services (83.1%) and/or the criminal justice system (70.6%) before entering the forensic system. A history of elopement (31.5%) and inpatient aggression was high (60.6%). Most had a psychotic spectrum disorder (81.6%) and over half had a substance use disorder (57.2%) in the reporting year. A range of index offences was observed (69.9% violent, 20.3% general, 9.8% sexual), and the majority of the sample (61.0%) had an index offence that resulted in no injury or a minor injury to the victim. CONCLUSION: The Canadian forensic psychiatry system is comprised of a unique subset of justice-involved individuals. This study provides a detailed examination of accused who are subject to the jurisdiction of the ORB and provides key insight into risk factors associated with offending behaviour in this population. The results of this study will provide a framework for future studies examining the association between mental disorder and violence and the treatment trajectories for those in the forensic psychiatry system.

Fitness to Drive: A Smartphone Application for Doctors, Patients and the Driver Licensing Authority.

Medical fitness to drive in Victoria is currently governed by the Austroads Fitness to Drive Guidelines. Doctors are expected to review the 188-page document and advise patients in relation to their unique medical condition. Patients must then report themselves to the driver licensing authority if they are unfit to drive. Despite multiple recommendations from coroners, there is no mandatory reporting system in Victoria, as mandatory reporting is disliked by both doctors and patients. Research has shown that binary decision trees are more accurate than doctors in determining fitness to drive. This article proposes a phone application implementing yes-no decision trees for each condition in the guidelines to increase accuracy and documentation rates and protect doctors from liability.

Helical tomotherapy for asymptomatic chemotherapy-refractory or -unfit multiple (3 or more) metastases.

Background: Despite chemotherapy innovations, prognosis of patients with chemotherapy-refractory or -unfit multiple metastases (CRMM/CUMM) remains poor. In this prospective study, the efficacy and toxicity of helical tomotherapy for CRMM/CUMM were evaluated. Materials and methods: Between 2014 and 2020, asymptomatic patients with CRMM/CUMM with ≥ 3 lesions and no prior radiotherapy of the targets were enrolled. Patients who had intolerable toxicities to chemotherapy and those who refused chemotherapy were included in the CRMM and CUMM groups, respectively. Prostate cancer patients and patients with metastases mainly localized in the liver, lung, or brain were excluded. By helical tomotherapy, up to 10 lesions per patient were irradiated in order of volume. The standard dose was 50-60 Gy in 25-30 fractions. Results: Forty-five patients (median age, 63 years; 35 CRMM/10 CUMM) were enrolled. Primary tumors included lung, gynecological, and gastrointestinal cancers. The most frequently treated targets were lymph node metastases, followed by peritoneal/pleural disseminations and bone tumors. The 1-year survival rate was 51% (median, 12.5 months). In the 35 patients with CRMM, the median survival time was 12.5 months, and the median pre-radiation chemotherapy period was 8.8 months (p > 0.05). The 6-month target control rate was 78%. Acute adverse events (grade ≥ 2) occurred in 33 patients: hematologic toxicities in 23, dermatitis in 6, and others in 8. Late grade ≥ 2 toxicities occurred in 6 patients: pneumonitis in 4 and gastric hemorrhage in 2. Conclusion: Tomotherapy for CRMM/CUMM resulted in median survival times > 1 year. This treatment should be investigated further in larger prospective studies.

Treatment patterns and outcomes of unfit and elderly patients with Mantle cell lymphoma unfit for standard immunochemotherapy: A UK and Ireland analysis.

Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progression-free survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8·7-21·2) and median OS was 31·4 months (95% CI 19·7-43·2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2·90, P = 0·01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0·49, P = 0·02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2·14, P = 0·04), blastoid morphology (HR 4·08, P = 0·001) and progression of disease at <24 months status (HR 5·68, P < 0·001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors in this specific clinical setting are warranted.

Endometrial Cancer: When Upfront Surgery Is Not an Option.

Background and Summary: The management of endometrial cancer, in an ever-older population with considerable comorbidity, remains a challenge for gynecological and radiation oncologists. Key Message: The present paper reviews literature data on treatment options for endometrial cancer patients unfit for surgery.

Treatment options for older unfit patients with acute myeloid leukemia.

Older acute myeloid leukemia patients usually experience a bleak outcome, especially those in the unfit group. For this unfit category, intensive chemotherapy and allogeneic stem cell transplantation are usually accompanied by higher early mortality, which results from higher risk genetic profiles and worse psychological and physiological conditions. The significant improvement in genetic technology recently has driven the appearance of several mutation-targeted therapies, such as FLT3, Bcl-2, IDH and Hedgehog pathway inhibitors and an anti-CD33 antibody-drug conjugate, which have changed enormously the therapeutic landscape of acute myeloid leukemia. This review describes the treatment dilemma of the unfit group and discusses the objective clinical data of each targeted drug and mechanisms of resistance, with a focus on combination strategies with fewer toxicities and abrogation of drug resistance.

[Investigation of the reduction in the disability after fractures in children and adolescents]. / Ermittlung der Minderung der Erwerbsfähigkeit nach Frakturen bei Kindern und Jugendlichen.

The student accident insurance has been part of the German Statutory Accident Insurance (Deutsche Gesetzliche Unfallversicherung, DGUV) for 50 years. In order to assess the reduction in working capacity (Minderung der Erwerbsfähigkeit, MdE) in the event of permanent consequences of accidents and injuries, the recommendation to treat the affected child or adolescent "as an average adult" is currently still valid. The present work deals with the everyday practice of the MdE assessment in children and adolescents and their weaknesses through the transfer of the principles from adulthood. In addition, proposals for the adaptation of the assessment principles for the growth age are drawn up.

[Stratified treatment of fit and unfit acute myeloid leukemia].

The etiology and pathogenesis of acute myeloid leukemia (AML) have been elucidated at chromosomal and genetic levels. The classification and prognosis for its treatment has clearly involved specific chromosomal aberrations and genetic mutations. The recent comprehensive genomic analysis represented by next-generation sequencers has led to discovering new genetic mutations in AML. These findings have not only been applied clinically as prognostic factors and MRD markers but also contributed to the development of new molecular-targeting drugs. Many new drugs have already been approved in the USA and Europe, and new stratified treatments have tried to incorporate them. With the advent of venetoclax, treatment strategies, especially for patients with poor prognosis and who are unfit, have been substantially revised, and the maintenance therapy for AML is also being reevaluated in accordance to the National Comprehensive Cancer Network guidelines. This article will review the current status of AML treatment in Japan and according to Western guidelines.