Distinguishing pathophysiological features of heart failure with reduced and preserved ejection fraction: A comparative analysis of two mouse models.

Heart failure (HF) is a heterogeneous condition that can be categorized according to the left ventricular ejection fraction (EF) into HF with reduced (HFrEF) or preserved (HFpEF) EF. Although HFrEF and HFpEF share some common clinical manifestations, the mechanisms underlying each phenotype are often found to be distinct. Identifying shared and divergent pathophysiological features might expand our insights on HF pathophysiology and assist the search for therapies for each HF subtype. In this study, we evaluated and contrasted two new murine models of non-ischaemic HFrEF and cardiometabolic HFpEF in terms of myocardial structure, left ventricular function, gene expression, cardiomyocyte calcium handling, mitochondrial polarization and protein acetylation in a head-to-head fashion. We found that in conditions of similar haemodynamic stress, the HFrEF myocardium underwent a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation was greater in the HFpEF myocardium. We observed opposing features on calcium release, which was diminished in the HFrEF cardiomyocyte but enhanced in the HFpEF cardiomyocyte. Mitochondria were less polarized in both HFrEF and HFpEF cardiomyocytes, reflecting similarly impaired metabolic capacity. Hyperacetylation of cardiac proteins was observed in both models, but it was more accentuated in the HFpEF heart. Despite shared features, unique triggering mechanisms (neurohormonal overactivation in HFrEF vs. inflammation in HFpEF) appear to determine the distinct phenotypes of HF. The findings of the present research stress the need for further exploration of the differential mechanisms underlying each HF subtype, because they might require specific therapeutic interventions. KEY POINTS: The mechanisms underlying heart failure with either reduced (HFrEF) or preserved (HFpEF) ejection fraction are often found to be different. Previous studies comparing pathophysiological traits between HFrEF and HFpEF have been conducted on animals of different ages and strains. The present research contrasted two age-matched mouse models of non-ischaemic HFrEF and cardiometabolic HFpEF to uncover divergent and shared features. We found that upon similar haemodynamic stress, the HFrEF heart experienced a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation appeared to be greater in the HFpEF myocardium. Calcium release was diminished in the HFrEF cardiomyocyte and enhanced in the HFpEF cardiomyocyte. Mitochondria were comparably less polarized in both HFrEF and HFpEF myocytes. Hyperacetylation of proteins was common to both models, but stronger in the HFpEF heart. Casting light on common and distinguishing features might ease the quest for phenotype-specific therapies for heart failure patients.

An FDA-Validated, Self-Cleaning Liquid Chromatography-Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium.

As organoids and organ-on-chip (OoC) systems move toward preclinical and clinical applications, there is an increased need for method validation. Using a liquid chromatography-mass spectrometry (LC-MS)-based approach, we developed a method for measuring small-molecule drugs and metabolites in the cell medium directly sampled from liver organoids/OoC systems. The LC-MS setup was coupled to an automatic filtration and filter flush system with online solid-phase extraction (SPE), allowing for robust and automated sample cleanup/analysis. For the matrix, rich in, e.g., protein, salts, and amino acids, no preinjection sample preparation steps (protein precipitation, SPE, etc.) were necessary. The approach was demonstrated with tolbutamide and its liver metabolite, 4-hydroxytolbutamide (4HT). The method was validated for analysis of cell media of human stem cell-derived liver organoids cultured in static conditions and on a microfluidic platform according to Food and Drug Administration (FDA) guidelines with regards to selectivity, matrix effects, accuracy, precision, etc. The system allows for hundreds of injections without replacing chromatography hardware. In summary, drug/metabolite analysis of organoids/OoCs can be performed robustly with minimal sample preparation.

Early detection of pancreatic cancer in the era of precision medicine.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality and it is often diagnosed at advanced stages due to non-specific clinical presentation. Disease detection at localized disease stage followed by surgical resection remains the only potentially curative treatment. In this era of precision medicine, a multifaceted approach to early detection of PDAC includes targeted screening in high-risk populations, serum biomarkers and "liquid biopsies", and artificial intelligence augmented tumor detection from radiologic examinations. In this review, we will review these emerging techniques in the early detection of PDAC.

Mitochondrial Ca2+ Uniporter-Dependent Energetic Dysfunction Drives Hypertrophy in Heart Failure.

The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)-induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B-dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin-independent protein kinase II/cyclic adenosine monophosphate response element-binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.

Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objectives: There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients. Methods: A retrospective review of a single center, prospective database (1994-2021) was performed to identify patients with rare ovarian malignancies treated with CRS/HIPEC. Clavien-Dindo 90-day morbidity/mortality and Kaplan-Meier overall (OS) and progression-free survival (PFS) were analyzed. Results: Of 44 patients identified, 28 underwent CRS/HIPEC. Six were aborted due to extensive disease. Histologic subtypes included: clear cell (5/28, 17.9 %), endometrioid (5/28, 17.9 %), granulosa cell (3/28, 10.7 %), low-grade serous (6/28, 21.4 %), mesonephric (1/28, 3.6 %), mucinous (6/28, 21.4 %), and small cell (2/28, 7.1 %) carcinomas. Eight (28.6 %) patients had primary and 20 (71.4 %) had recurrent disease. Median peritoneal cancer index (PCI) was 21 (IQR: 6-29). Complete cytoreduction (<2.5 mm residual disease) was achieved in 27/28 (96.4 %). Grade III/IV complications occurred in 9/28 (32.1 %) with one (3.6 %) mortality. After a median follow-up of 65.8 months, 20 patients were alive. Five-year OS and PFS were 68.5 and 52.6 %, respectively. Conclusions: In patients with PM from rare ovarian malignancies, CRS/HIPEC is feasible and has an acceptable safety profile. Longer follow-up and multicenter trials are needed.

Collaborative expertise of gynecological and surgical oncologists in managing advanced epithelial ovarian cancer.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) present with significant peritoneal spread. We assessed collaborative efforts of surgical and gynecological oncologists with expertise in cytoreductive surgery (CRS) in the management of advanced EOC. METHODS: Using a prospective single-center database (2014-2022), we described the operative and oncologic outcomes of stage IIIC-IVA primary and recurrent EOC perioperatively managed jointly by gynecological and surgical oncologists both specializing in CRS and presented components of this collaboration. RESULTS: Of 199 identified patients, 132 (66 %) had primary and 53 (27 %) had recurrent EOC. Due to inoperable disease, 14 (7 %) cases were aborted and excluded from analysis. Median peritoneal cancer index (PCI) in primary and recurrent patients was 21 (IQR: 11-28) and 21 (IQR: 6-31). Upper abdominal surgery was required in 95 % (n = 125) of primary and 89 % (n = 47) of recurrent patients. Bowel resections were performed in 83 % (n = 110) and 72 % (n = 38), respectively. Complete cytoreduction (CC-0/1) with no disease or residual lesions <2.5 mm was achieved in 95 % (n = 125) of primary and 91 % (n = 48) of recurrent patients. Ninety-day Clavien-Dindo grade III-IV morbidity was 12 % (n = 16) and 21 % (n = 11), respectively. Median follow-up was 44 (95%CI: 33-55) months. Median overall survival in primary and recurrent EOC was 68 (95%CI: 45-91) and 50 (95%CI: 16-84) months. Median progression-free survival was 26 (95%CI: 22-30) and 14 (95%CI: 7-21) months, respectively. CONCLUSIONS: Perioperative collaboration between surgical and gynecological oncologists specializing in CRS allows safe performance of complete cytoreduction in the majority of patients with primary and recurrent EOC, despite high tumor burden.

Previous cardiovascular injury is a prerequisite for immune checkpoint inhibitor-associated lethal myocarditis in mice.

AIMS: Immune checkpoint inhibitors (ICIs) are antineoplastic drugs designed to activate the immune system's response against cancer cells. Evidence suggests that they may lead to immune-related adverse events, particularly when combined (e.g., anti-CTLA-4 plus anti-PD-1), sometimes resulting in severe conditions such as myocarditis. We aimed to investigate whether a previously sustained cardiac injury, such as pathological remodelling due to hypertension, is a prerequisite for ICI therapy-induced myocarditis. METHODS: We evaluated the cardiotoxicity of ICIs in a hypertension (HTN) mouse model (C57BL/6). Weekly doses were administered up to day 21 after the first administration. Our analysis encompassed the following parameters: (i) survival and cardiac pathological remodelling, (ii) cardiac function assessed using pressure-volume (PV)-loops, with brain natriuretic peptide (BNP) serving as a marker of haemodynamic dysfunction and (iii) cardiac inflammation (cytokine levels, infiltration, and cardiac antigen autoantibodies). RESULTS: After the first administration of ICI combined therapy, the treated HTN group showed a 30% increased mortality (P = 0.0002) and earlier signs of hypertrophy and pathological remodelling compared with the untreated HTN group. BNP (P = 0.01) and TNF-α (<0.0001) increased 2.5- and 1.7-fold, respectively, in the treated group, while IL-6 (P = 0.8336) remained unchanged. Myocarditis only developed in the HTN group treated with ICIs on day 21 (score >3), characterised by T cell infiltration and increased cardiac antigen antibodies (86% showed a titre of 1:160). The control group treated with ICI was unaffected in any evaluated feature. CONCLUSIONS: Our findings indicate that pre-existing sustained cardiac damage is a necessary condition for ICI-induced myocarditis.

Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation.

Skeletal muscle relies on mitochondria for sustainable ATP production, which may be impacted by reduced oxygen availability (hypoxia). Compared with long-term hypoxia, the mechanistic in vivo response to acute hypoxia remains elusive. Therefore, we aimed to provide an integrated description of the Musculus gastrocnemius response to acute hypoxia. Fasted male C57BL/6JOlaHsd mice, fed a 40en% fat diet for six weeks, were exposed to 12% O2 normobaric hypoxia or normoxia (20.9% O2) for six hours (n = 12 per group). Whole-body energy metabolism and the transcriptome response of the M. gastrocnemius were analyzed and confirmed by acylcarnitine determination and Q-PCR. At the whole-body level, six hours of hypoxia reduced energy expenditure, increased blood glucose and tended to decreased the respiratory exchange ratio (RER). Whole-genome transcriptome analysis revealed upregulation of forkhead box-O (FOXO) signalling, including an increased expression of tribbles pseudokinase 3 (Trib3). Trib3 positively correlated with blood glucose levels. Upregulated carnitine palmitoyltransferase 1A negatively correlated with the RER, but the significantly increased in tissue C14-1, C16-0 and C18-1 acylcarnitines supported that ß-oxidation was not regulated. The hypoxia-induced FOXO activation could also be connected to altered gene expression related to fiber-type switching, extracellular matrix remodeling, muscle differentiation and neuromuscular junction denervation. Our results suggest that a six-hour exposure of obese mice to 12% O2 normobaric hypoxia impacts M. gastrocnemius via FOXO1, initiating alterations that may contribute to muscle remodeling of which denervation is novel and warrants further investigation. The findings support an early role of hypoxia in tissue alterations in hypoxia-associated conditions such as aging and obesity.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. METHODS: A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). RESULTS: We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). CONCLUSIONS: After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal dissemination from ovarian carcinosarcoma.

BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon and aggressive malignancy, with poor response to current treatment approaches and no clear guidelines. Our aim is to evaluate the outcomes of an OCS cohort after cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A descriptive cohort study was performed. Patients who underwent CRS/HIPEC for peritoneal dissemination from tubo-ovarian malignancies (1999-2021) were retrospectively reviewed. Patients with confirmed histopathologic diagnosis of FIGO stage III/IV OCS were included. Overall (OS) and progression-free survival (PFS) were determined with the Kaplan-Meier method. RESULTS: Of 267 patients with tubo-ovarian malignancies reviewed, 7.5% (20/267) had OCS. Of these, 16 underwent CRS/HIPEC, including 9 for a new diagnosis and 7 for disease recurrence. Median age at surgery was 66.5 (IQR: 54.5-74.5) years. Nine (56.2%) patients were FIGO stage IV. Median peritoneal cancer index was 22 (IQR: 14-28). Complete cytoreduction was achieved in 15/16 (93.7%) cases. HIPEC agents included carboplatin (n = 7), cisplatin+doxorubicin (n = 4), and melphalan (n = 5). Major complications occurred in 4/16 (25%), with no 90-day mortality. Median follow-up was 41.8 months. Median PFS was 11.7 (95%CI: 10.5-17.1) months. Malignant bowel obstruction occurred in 3/16 (18.7%). Median OS from CRS/HIPEC was 21.3 (95%CI: 16.3-31.6) months, not reached for newly diagnosed vs 19.7 months for recurrent patients (p = 0.23). CONCLUSIONS: CRS/HIPEC showed promising survival and abdominal disease control with low rates of malignant obstruction in patients with advanced stage OCS. Collaborative studies with larger cohorts and longer follow-up may further elucidate the role of CRS/HIPEC in OCS.

Volumen plaquetario medio e índice de plaquetas-linfocitos como factores de pronóstico en cáncer papilar de tiroides.

BACKGROUND: Papillary thyroid cancer is the most common endocrine neoplasia. There are prognostic factors that establish risk of recurrence and mortality; however, patients considered low risk may have a less favorable evolution and hence the importance of finding new markers. OBJECTIVE: To assess whether the mean platelet volume (MPV) and the platelet-lymphocyte index (PLI) show a relationship with the clinical staging in papillary thyroid cancer. METHOD: Retrospective, observational and analytical study. Preoperative MPV and PLI were recorded, its relationship with TNM and MACIS systems was sought, as well as locally advanced invasion and tumor focality. RESULTS: 107 cases treated from November 2017 to February 2020. No statistically significant difference was observed in these two preoperative parameters with advanced and initial stages, risk groups or tumor focality. The statistical analysis used was one-way ANOVA with SPSS 25, a 95% confidence interval and p < 0.05. CONCLUSIONS: Despite the logical reasoning of tumor pathophysiology, our study did not find a relationship between papillary thyroid carcinoma with MPV and PLI, and should be complemented with more extensive studies.

ANTECEDENTES: El cáncer papilar de tiroides es la neoplasia endocrina más frecuente. Existen factores pronósticos que establecen el riesgo de recurrencia y mortalidad; sin embargo, los pacientes considerados de bajo riesgo pueden llegar a presentar una evolución menos favorable, y de ahí la importancia de encontrar nuevos marcadores. OBJETIVO: Evaluar si el volumen plaquetario medio (VPM) y el índice plaquetas-linfocitos (IPL) presentan una relación con la etapificación clínica en el cáncer papilar de tiroides. MÉTODO: Estudio retrospectivo, observacional y analítico. Se registraron el VPM y el IPL preoperatorios, y se buscó su relación con los sistemas TNM y MACIS, así como con la invasión localmente avanzada y la focalidad del tumor. RESULTADOS: Se trataron 107 casos de noviembre de 2017 a febrero de 2020. No se observó diferencia estadísticamente significativa en estos dos parámetros preoperatorios o en estadios avanzados e iniciales, grupos de riesgo ni focalidad del tumor. El análisis estadístico utilizado fue ANOVA de una vía, con SPSS 25, con intervalo de confianza del 95% y p < 0.05. CONCLUSIONES: Pese al razonamiento lógico de la fisiopatología tumoral, en nuestro estudio no se encontró relación entre el carcinoma papilar de tiroides, el VPM y el IPL, y debiera complementarse con estudios más extensos.

Targeting the mitochondrial Ca2+ uniporter complex in cardiovascular disease.

Cardiovascular diseases (CVDs), the leading cause of death worldwide, share in common mitochondrial dysfunction, in specific a dysregulation of Ca2+ uptake dynamics through the mitochondrial Ca2+ uniporter (MCU) complex. In particular, Ca2+ uptake regulates the mitochondrial ATP production, mitochondrial dynamics, oxidative stress, and cell death. Therefore, modulating the activity of the MCU complex to regulate Ca2+ uptake, has been suggested as a potential therapeutic approach for the treatment of CVDs. Here, the role and implications of the MCU complex in CVDs are presented, followed by a review of the evidence for MCU complex modulation, genetically and pharmacologically. While most approaches have aimed within the MCU complex for the modulation of the Ca2+ pore channel, the MCU subunit, its intra- and extra- mitochondrial implications, including Ca2+ dynamics, oxidative stress, post-translational modifications, and its repercussions in the cardiac function, highlight that targeting the MCU complex has the translational potential for novel CVDs therapeutics.

Specific plasticity of the anemone Anthopleura hermaphroditica to intertidal and subtidal environmental conditions of the Quempillén estuary.

The cellular capacity of marine organisms to address rapid fluctuations in environmental conditions is decisive, especially when their bathymetric distribution encompasses intertidal and subtidal zones of estuarine systems. To understand how the bathymetric distribution determines the oxidative damage and antioxidant response of the estuarine anemone Anthopleura hermaphroditica, individuals were collected from upper intertidal and shallow subtidal zones of Quempillén River estuary (Chile), and their response analysed in a fully orthogonal, multifactorial laboratory experiment. The organisms were exposed to the effects of temperature (10°C and 30°C), salinity (10 ppt and 30 ppt) and radiation (PAR, > 400-700 nm; PAR+UV-A, > 320-700 nm; PAR+UV-A+UV-B, > 280-700 nm), and their levels of lipid peroxidation, protein carbonyl and total antioxidant capacity were determined. The results indicated that the intertidal individuals of A. hermaphroditica presented higher levels of tolerance to the stressful ranges of temperature, salinity, and radiation than individuals from the subtidal zone, which was evident from their lower levels of oxidative damage to lipids and proteins. These results were consistent with increased levels of total antioxidant capacity observed in subtidal organisms. Thus intertidal individuals could have greater plasticity to environmental variations than subtidal individuals. Future studies are needed to understand the mechanisms underlying stress adaptation in individuals from this estuarine anemone subjected to different environmental stressors during their life cycles.

Safety of Nephrectomy Performed During CRS/HIPEC: A Propensity Score-Matched Study.

BACKGROUND: Surgeons may hesitate to perform nephrectomy (NE) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) due to a potential increase in morbidity. However, no data are available regarding the impact of NE on outcomes, so the authors decided to assess its safety during CRS/HIPEC. METHODS: A single-center propensity score-matched study was conducted using a prospective database (1994-2021). The study included patients who underwent NE during CRS/HIPEC with completeness of cytoreduction (CC) of 0, 1, or 2. Control subjects (no-NE) were selected in a 1:3 ratio using propensity score-matching weighted by age, histology, peritoneal cancer index (PCI), CC-0 or CC-1 rate, and length of surgery. RESULTS: Among 828 patients, 13 NE and 39 no-NE control subjects were identified. The indications for NE included tumor involvement of the ureter, hilum, and/or kidney with preserved (n = 8), decreased (n = 2), or absent (n = 3) function. NE patients received more intraoperative intravenous (IV) fluids (16,000 vs 11,500 mL; p = 0.045) and had a greater urine output (3200 vs 1913 mL; p = 0.008). NE patients received mitomycin C (40 mg for 90 min) or melphalan (50 mg/m2 for 90 min) without reduction of dose or time. Major morbidity (p = 0.435) and mortality (p = 1.000) were comparable between the two groups. No postoperative acute kidney injury was seen in either group. Adjuvant chemotherapy was administered to 46.2% of the NE and 35.9% of the no-NE patients (p = 0.553), with similar starting times (p = 0.903) between the groups. CONCLUSIONS: Nephrectomy performed during CRS/HIPEC does not seem to increase postoperative morbidity or to delay adjuvant chemotherapy, and NE can be performed if required for complete cytoreduction. The NE patients in our cohort did not have a reduction of mitomycin C or melphalan dose or perfusion time.

Adjuvant chemotherapy for high-grade appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: There are no available data on the efficacy of adjuvant chemotherapy (ACT) in stage IVA/B high-grade mucinous appendiceal cancer treated with CRS/HIPEC. We evaluated the association between ACT and survival in this cohort. MATERIALS AND METHODS: A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade mucinous appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1 were included. Survival was compared between ACT and no chemotherapy (NoCT) patients. Subgroup analysis was performed with adjustment for confounding variables. RESULTS: We identified 180 patients: 77 ACT and 103 NoCT. ACT regimens included 5-FU/capecitabine (13%), oxaliplatin-based (63%), and irinotecan-based (21%), combined with bevacizumab in 27% of cases. Median number of cycles was 9 (IQR: 6-12). Median overall survival (OS) did not significantly differ between ACT and NoCT (53 vs 75 months, p = 0.566). Multivariable Cox regression showed no OS benefit for ACT vs NoCT in patients with neoadjuvant chemotherapy (HR 1.14; 95%CI: 0.38-3.39) or without it (HR 1.33; 95%CI: 0.69-2.57), with signet ring cell (HR 0.89; 95%CI: 0.38-2.06) or other histologies (HR 1.11; 95%CI: 0.50-2.46), positive lymph nodes (HR 1.60; 95%CI: 0.74-3.49), or peritoneal cancer index ≥20 (HR 1.08; 95%CI: 0.55-2.11) after adjusting for other factors. CONCLUSIONS: In our cohort, colon-type ACT was not associated with better OS in stage IVA/B mucinous appendiceal cancer after CRS/HIPEC, even after adjusting for confounders. This may be due to different tumor biology than colon cancer or small sample size. Prospective collaborative studies are needed.

Improved Walk Test Performance and Blood Pressure Responses in Men and Women Completing Cardiac Rehabilitation: Implications Regarding Exercise Trainability.

Purpose. To evaluate changes in walk test performance and blood pressure (BP) responses following a 12-week exercise-based outpatient cardiac rehabilitation (CR) program. Methods. Six-Minute Walk Test (6MWT) and resting systolic BP (SBP), diastolic BP (DBP), post-6MWT heart rate (HR), and post-6MWT BPs were measured before and after CR in 311 (237 men,74 women) patients. Using age as a covariate, 2 by 2 (Gender × Measurement) ANCOVAs were used to determine differences in 6MWT performance and hemodynamic variables. Results. After adjusting for age, men covered a greater 6MWT distance than women; pre-CR versus post-CR program values are as follows: men, 429.3 ± 94.6 versus 557.6 ± 90.7 m, P ≤ .001; women, 374.9 ± 100.7 versus 483.2 ± 82.9 m, P ≤ .001. Both genders reduced resting DBP following the CR program (men: 67.2 ± 9.8 vs 65.6 ± 8.5 mm Hg, P = .034; women: 69.2 ± 10.7 vs 65.0 ± 8.0 mm Hg, P = .001) and increased HR following the 6MWT after the CR program (men: 97.7 ± 16.8 vs 112.7 ± 21.3 bpm, P ≤ .001; women: 100.7 ± 20.8 vs 110.2 ± 22.0 bpm, P ≤ .001). Similarly, SBP increased immediately following the 6MWT (122.8 ± 18.5 vs 133.6 ± 20.7 mm Hg; P ≤ .001) in men but not in women. Conclusion. The present findings indicate similar relative improvements in 6MWT performance and BP responses in adherent men and women following an exercise-based CR program.