Are Subacute Care Patients Living Longer?

In order to provide prognostic information for gerontologists who regularly counsel families, we determined to measure the longevity of subacute patients who have feeding tubes and tracheostomies. This study compares two cohorts of patients: 2002-2006 and 2015-2019. T-tests were performed to compare the total days in acute care, the total survival days, and the number of hospital admissions between the two groups. Results revealed (2002-2006, 2015-2019), some variance in the acute care days between the two groups (M= 15.4186, 21.49438) and p= .66. There is a wide difference in the total survival days between the two groups with individuals from 2015-2019 living longer than 2002-2006 (M= 229.8198, 644.0449), p< .001. However, there is no statistically significant difference in the number of hospital admissions between the two groups (M= 0.994186, 0.7752809), p= .09754. We hypothesize that advances in technology, medicine, and care over the span of 17 years contribute to increased longevity. On average, patients in the 2015-2019 group survived 414 days longer than the first group. Yet, even with such advances, more days were spent in acute care in the second group (2015-2019). Our data show subacute longevity has nearly tripled in the last decade. Although patients are living longer, they are often in a vegetative state; in most instances, there is no apparent improvement in quality of life. This study provides current data which will help gerontologists improve prognostication and allow them to form a more realistic long view of care.

Improving Outcomes for Patients with Multiple Myeloma through the Optimization of Treatment Sequences

Introduction: Multiple myeloma (MM) is an incurable disease characterized by the proliferation of malignant plasma cells within the bone marrow, causing a wide range of burdensome symptoms. Patients initiating treatment typically receive a combination of drugs across various classes with or without autologous stem cell transplantation (ASCT). However, patients will invariably relapse following initial treatment, and often require many lines of drug treatment over the course of their disease. Real-word data showed that a significant proportion of newly diagnosed MM patients that receive frontline (FL) treatment did not receive subsequent treatment. These high attrition rates suggest that using the best treatment upfront is crucial in delaying disease progression. The CASSIOPEIA (transplant-eligible [TE] setting), MAIA and ALCYONE (transplant-ineligible [TIE] setting) trials demonstrate that the addition of daratumumab (DARA) to standard of care treatments in FL significantly improves patient outcomes. Based on data from these trials, the European marketing authorization for DARA has been extended to the FL setting. To ensure the best possible long-term patient outcomes in clinical practice, the availability of new FL treatment options requires a redefinition of treatment patterns. Thus, we aim to investigate whether the adoption of DARA as a FL, as opposed to later-line, treatment of MM leads to better outcomes and improved clinical practice. Methods: In the absence of real-world sequencing data, we developed a clinical sequencing simulation using individual patient data from the DARA trials and indirect comparative evidence, across all indications in MM. We used progression-free survival curves to simulate health state transition probabilities across four lines of active treatment, to capture the efficacy of treatment sequences in MM. Patients start with initiation of FL treatment, and ASCT eligibility determines the sequences patients receive. Clinical expert opinion was sought to determine 1) the full range of meaningful treatment sequences and 2) which of these are used most in Italian clinical practice. Based on the clinical simulation outcomes, we calculated average time spent in each line of treatment, percentage of patients alive at different timepoints, and the total survival for patients initiating a sequence. This analysis included conservative attrition rates from trial data, 14% for TE (CASSIOPEIA) and 24% for TIE (MAIA/ALCYONE), assumed as similar across regimens in each setting. Results: In the TE setting, the best outcomes were achieved when using the DARA-based regimen (DVTd) as FL treatment, followed by either a LEN-based regimen (KRd) or a BOR-based regimen (PVd), resulting in a total survival of 14.2 and 14.1 years, respectively. In the TIE setting, the best outcomes were achieved when DRd or DVMP were used as FL treatment, followed by either a BOR-based regimen (PVd, for DRd) or a LEN-based regimen (KRd, for DVMP), resulting in a total survival of 11.7 and 10.9 years, respectively. In both the FL and second line (2L) settings, there was a clear survival benefit of using DARA. When comparing the DARA-based sequence with the current FL TE benchmark sequence (DVTd + KRd + Pd + Vd versus VTd + DRd + Kd + Pd), an additional survival of 1.5 years was observed in TE patients. When DARA was added to the current FL TIE benchmark sequence (DRd + PVd + Kd + Vd versus VMP + DRd + Kd + Pd), TIE patients lived on average 2.8 years longer. For TE patients, time spent progression-free ranged from an average of 4.83 to 7.99 years at FL, 1.42 to 5.40 years in 2L, 0.23 to 2.24 years in 3L and 0.17 to 1.53 years on 4L. For TIE patients, the variation was higher, leaving more room for optimization: 1.97 to 7.31 years at FL, 0.68 to 4.76 years in 2L, 0.17 to 3.25 years in 3L and 0.19 to 0.51 years in 4L. Conclusion: To our knowledge, this is the first sequencing simulation to consider optimal patient outcomes across several lines of MM treatment. The results show that the longest time in remission is achieved with the use of DARA-based regimens as FL treatment, significantly improving patient outcomes. Time spent progression free decreases with each subsequent line of treatment and the magnitude of the effect seen in the third and fourth treatment lines is not as significant as that of the effect seen in earlier treatment lines. Therefore, patients should be treated with the most effective treatment upfront. Disclosures Petrucci: Celgene: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board. Mendes: Janssen-Cilag Farmacêutica: Current Employment. Boer: Janssen: Consultancy. Casamassima: Janssen: Current Employment. Willis: Janssen: Consultancy. Wadlund: Janssen: Current Employment. Matthijsse: Janssen: Consultancy. Armeni: Astrazeneca: Consultancy; Boehringer Ingelheim: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; Johnson & Johnson: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy

It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.

Absence of WDR13 in p53-Null Mice Increases Longevity

Absence of WDR13 is known to be involved in pancreatic, colon and uterine hyperproliferation. However, a recent study showed its antiproliferative role liver regeneration in response to hepatotoxins. These findings intrigued to study the role of WDR13-null condition in Trp53 knockout mouse to study the tumour predisposition and survival. We report absence of Wdr13 in Trp53-null background alleviates the tumour load, in turn increasing total survival in mouse model.

NQPC-02 Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study

Purpose: In the present study, we performed a retrospective review of patients receiving carboplatin based chemotherapy followed by radiotherapy for newly diagnosed primary intracranial germ cell tumors. In order to identify an optimal germ cell tumor treatment strategy, we evaluated treatment outcomes and toxicity and compliance. Methodology: This study included 110 consecutive patients with newly diagnosed primary intracranial germ cell tumors. The drug doses and administration schedule of carboplatin-etoposide (CARB-VP) were as follows: carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 on days 1 to 3). Ifosfamide-carboplatin-etoposide (ICE) treatment comprised ifosfamide (1500 mg/m2 daily for 3 days), carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 daily for 3 days). Patients with germinomatous germ cell tumors (pure germinoma or germinoma with STGC) basically receive three cycles of CARB-VP and a total dose of 30Gy whole ventricular radiotherapy. We delivered combination therapy consisting of combined ICE chemotherapy and craniospinal irradiation followed by the complete resection of the residual tumor for nongerminomatous malignant germ cell tumors. Results: The median follow-up time was 11.0 years (range, 0.5–37.8 years). The 5-year total survival rates of germinomatous and nongerminomatous germ cell tumors were 97.2% and 66.7%, respectively. The 10-year and 20-year total survival rates of germinomatous germ cell tumors were 95.7% and 90.0%, respectively. Adverse events related to carboplatin based chemotherapy are not detected. Furthermore, no treatment-related deaths were observed. Conclusions: Our treatment with surgery, carboplatin based chemotherapy followed by radiotherapy is effective in treating primary intracranial germ cell tumors, especially in germinomatous group.

Sarcopenia as a Prognostic Factor of Hepatotoxicity and Lower Survival Rate in Chemotherapy of Pancreatic Cancer

Aim. Evaluation of sarcopenia’s effect on hepatotoxicity in patients with locally advanced and metastatic pancreatic cancer (PC).Materials and methods. A retro-prospective study included 66 patients (30 men and 36 women) with locally advanced and metastatic PC receiving chemotherapy treatment in the form of gemcitabine monotherapy and in combination with platinum, taxanes, fluoropyrimidines in standard chemotherapy protocols. Sarcopenia was observed using computer tomography with intravenous bolus contrast and nonionic contrast medium with iodine concentration 350 mg/ml. Muscle tissue area (cm2) was estimated with two consecutive axial slices at the level of L3 lumbar vertebra. Sarcopenia was determined with the L3 skeletal muscle index (L3SMI) calculated as a ratio of skeletal muscle area at the L3 vertebra to patient’s height squared. Condition was marked as sarcopenia at L3SMI values of 52.4 cm2/m2 in men and 38.5 cm2/m2 in women.Results. Hepatotoxicity was revealed in 57.5% (n = 38) of PC patients receiving chemotherapy, with 60.87% (n = 28) of them having sarcopenia. In patients with sarcopenia and no toxic effects, the total survival median was 41 months, whilst hepatotoxicity combined with sarcopenia was associated with almost a 3 times lower median survival (14.1 months). A better survival trend was observed in a polychemotherapy cohort without sarcopenia, with the total survival median of 17.0 months compared to 15.2 months in such patients with sarcopenia (p = 0.781). A positive trend towards survival was observed in a hepatotoxicity-negative cohort, with the total survival median of 18.7 months compared to 16.9 months in PC patients with toxic side effects (p = 0.174).Conclusions. Sarcopenia may be used as a prognostic factor of lower survival rate and higher hepatotoxic effect of chemotherapy in patients with locally advanced and metastatic pancreatic cancer.

Expression of Serum PTTG1 in Laryngeal Carcinoma and Its Correlation to Prognosis

Objectives. The purpose of this study was to investigate serum pituitary tumor transforming gene (PTTG1) expression in laryngeal carcinoma and its relationship with the clinical pathological characteristics and prognosis.Methods. Expression of serum PTTG1 was measured by enzyme-linked immunosorbent assay in 110 patients with laryngeal carcinoma and 60 patients with vocal cord polyps. Expression of the serum PTTG1 levels relationship with the clinicopathological characteristics and prognosis were analyzed.Results. In laryngeal carcinoma patients’ serum, the PTTG1 median concentration was 141.43 pg/mL (interquartile range [IQR], 111.387 to 160.837 pg/mL), significantly higher than that of the vocal cord polyp group of 94.01 pg/mL (IQR, 81.26 to 108.59 pg/mL), and the difference was statistically significant (z=–6.715, P<0.001). PTTG1 expression with lymph node metastasis, clinical stage, and patients with laryngeal carcinoma was significantly correlated with the tumor differentiation degree (P<0.05). The total survival rate of the PTTG1 high expression group was significantly lower than the low expression group, and the difference of total survival time of the two groups was statistically significant (P<0.001).Conclusion. The PTTG1 expression level can be used as an index for evaluating prognosis of laryngeal cancer. High PTTG1 expression is one of the factors of poor prognosis of laryngeal carcinoma patients.

Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.

An endophytic fungus interacts with crown level and larval density to reduce the survival of eastern spruce budworm, Choristoneura fumiferana (Lepidoptera: Tortricidae), on white spruce (Picea glauca)

A two-year field study was carried out to determine whether inoculating white spruce, Picea glauca (Moench) Voss, with a native endophytic fungus, Phialocephala scopiformis DAOM 229536 Kowalski & Kehr (Helotiales, Ascomycota), decreased the performance of eastern spruce budworm, Choristoneura fumiferana Clemens, developing on these trees. Second instars were reared at three densities in the mid crown and at one density in the lower, mid, and upper crown. Larval survival (i.e., survival of larvae to pupation) was lower on endophyte-inoculated trees than on control trees in the mid crown and especially the upper crown but was similar in the lower crown, resulting in a significant interaction between endophyte and crown level. A similar but marginally insignificant interaction was observed for overall survival up to adult emergence (i.e., total survival). Larval survival and total survival were approximately 22% and 19% lower, respectively, when developing in the upper crown of endophyte-inoculated trees than in control trees. Larval survival remained relatively constant, with increased density on control trees but decreased with density on endophyte-inoculated trees, resulting in a significant interaction between endophyte and larval density. Sex ratios of emerged adults and wing lengths of emerged females were not influenced by the endophyte. Our results suggest that endophytic fungi could be useful additions to integrated pest management programs.

Is Right Sleeve Lower Lobectomy Necessary? Is It Safe?

Objectives The right sleeve lower lobectomy is the least used of the bronchial sleeve operations. There are only case-based studies in the literature. In this study, we compared this technique to those used in patients who underwent a right lower bilobectomy. Methods We retrospectively reviewed the data of patients who had been operated on due to non-small cell lung cancer (NSCLC) from January 2005 to December 2015 from a dataset that was formed prospectively. Of the 4,166 patients who underwent resections due to NSCLC, the files of those who had a right sleeve lower lobectomy (group S) and those who had a right lower bilobectomy (group B) were evaluated. The remaining 25 patients in group B and 18 patients in group S were compared in terms of demographic data, morbidity, hospitalization time, mortality, histopathology, recurrence, and total survival. Results No significant differences in the demographic or clinical characteristics were observed between the two groups, except that group S had more female patients. Postoperative complications developed in 52% of the patients in group B and 11.1% of the patients in group S (p = 0.006). Mean hospitalization time was 9.6 ± 3.6 (range, 6–19) days in group B and 6.72 ± 1.5 (range, 4–9) days in group S (p = 0.001). All patients received complete resections. The mean patient follow-up time was 42.9 months. No significant difference was found between local and distant recurrences (p = 1, p = 0.432). Mean survival time was 89.6 months (5-year rate = 73%), which was 90.6 months (5-year rate = 75.3%) in group B and 63.1 months (5-year rate = 69.3%) in group S (p = 0.82). Conclusion This technique allows for reduced filling of the thoracic cavity by a prolonged air leak and a reduced prevalence of complications. Additionally, the hospitalization time is shortened. It does not produce any additional mortality burden, and total survival and oncological outcomes are reliable. This technique can be used in selected patients at experienced centers.