Long-term outcomes of robot-assisted versus minimally invasive esophagectomy in patients with thoracic esophageal cancer: a propensity score-matched study.

BACKGROUND: Recently, robot-assisted minimally invasive esophagectomy (RAMIE) has gained popularity worldwide. Some studies have compared the long-term results of RAMIE and minimally invasive esophagectomy (MIE). However, there are no reports on the long-term outcomes of RAMIE in Japan. This study compared the long-term outcomes of RAMIE and MIE. METHODS: This retrospective study included 86 patients with thoracic esophageal cancer who underwent RAMIE or MIE at our hospital from June 2010 to December 2016. Propensity score matching (PSM) was employed, incorporating co-variables such as confounders or risk factors derived from the literature and clinical practice. These variables included age, sex, body mass index, alcohol consumption, smoking history, American Society of Anesthesiologists stage, comorbidities, tumor location, histology, clinical TNM stage, and preoperative therapy. The primary endpoint was 5-year overall survival (OS), and the secondary endpoints were 5-year disease-free survival (DFS) and recurrence rates. RESULTS: Before PSM, the RAMIE group had a longer operation time (min) than the MIE group (P = 0.019). RAMIE also exhibited significantly lower blood loss volume (mL) (P < 0.001) and fewer three-field lymph node dissections (P = 0.028). Postoperative complications (Clavien-Dindo: CD ≥ 2) were significantly lower in the RAMIE group (P = 0.04), and postoperative hospital stay was significantly shorter than the MIE group (P < 0.001). After PSM, the RAMIE and MIE groups consisted of 26 patients each. Blood loss volume was significantly smaller (P = 0.012), postoperative complications (Clavien-Dindo ≥ 2) were significantly lower (P = 0.021), and postoperative hospital stay was significantly shorter (P < 0.001) in the RAMIE group than those in the MIE group. The median observation period was 63 months. The 5-year OS rates were 73.1% and 80.8% in the RAMIE and MIE groups, respectively (P = 0.360); the 5-year DFS rates were 76.9% and 76.9% in the RAMIE and MIE groups, respectively (P = 0.749). Six of 26 patients (23.1%) in each group experienced recurrence, with a median recurrence period of 41.5 months in the RAMIE group and 22.5 months in the MIE group. CONCLUSIONS: Compared with MIE, RAMIE led to no differences in long-term results, suggesting that RAMIE is a comparable technique.

Hypokalemia, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear.Methods and Results: We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K+<3.5 mmol/L) and hyperkalemia (K+>5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary ß2-microglobulin to creatinine ratio ≥300 µg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors. CONCLUSIONS: Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Albumin-to-globulin ratio predicts clinical outcomes of heart failure with preserved ejection fraction in women.

Despite advances in medicine, heart failure with preserved ejection fraction (HFpEF) remains an increasing health concern associated with a high mortality rate. Research has shown sex-based differences in the clinical characteristics of patients with HF; however, definitive biomarkers for poor clinical outcomes of HFpEF in women are unavailable. We focused on the albumin-to-globulin ratio (AGR), a biomarker for malnutrition and inflammation and investigated its usefulness as a predictor of clinical outcomes of HFpEF in women. We measured the AGR in consecutive 224 women with HFpEF and 249 men with HFpEF. There were 69 cardiac events in women with HFpEF and 69 cardiac events in men with HFpEF during the follow-up period. The AGR decreased with advancing New York Heart Association functional class in women with HFpEF. Patients were categorized into three groups based on AGR tertiles. Kaplan-Meier analysis showed that among the three groups, the risk for cardiac events and HF-associated rehospitalizations was the highest in the lowest tertile in women with HFpEF. Univariate and multivariate Cox proportional hazard regression analyses showed that after adjustment for confounding risk factors, the AGR was an independent predictor of cardiac events and HF-associated rehospitalizations in women with HFpEF, but not in men with HFpEF. The addition of AGR to the risk factors significantly improved the net reclassification and integrated discrimination indices in women with HFpEF. This is the first study that highlights the significant association between the AGR and the severity and clinical outcomes of HFpEF in women. Addition of AGR to the risk factors improved its prognostic value for clinical outcomes, which indicates that this variable may serve as a useful clinical biomarker for HFpEF in women.

[A Case of Isolated Metachronous Splenic Metastasis after Rectal Cancer Surgery].

A 50-year-old woman underwent laparotomic anterior resection(D3)and total hysterectomy with bilateral adnexectomy (type 2, 3.0×4.5 cm, pT4a[SE], N1a, M1c2[ovary and peritoneum], H0, P1, PUL0, stage Ⅳc, tub2>por, Cur B)for ovarian metastasis from rectal cancer in June 20XX. During the outpatient visit in May, 2 years and 11 months after surgery, a splenic tumor was found on abdominal contrast-enhanced CT, without distant metastasis in other organs. In July 20XX, laparoscopic splenectomy was performed for suspected splenic metastasis of rectal cancer. The specimen of the resected tumor showed pathological findings consistent with metastasis of rectal cancer. Currently, the patient is being followed up without any sign of recurrence. Herein, we report a rare case of isolated metachronous splenic metastasis, whose associated prognosis might be improved by surgical treatment, in reference to the literature.

[A Case of Diffuse Large B-Cell Lymphoma of the Testis, Which Also Developed in the Rectum after Resection of a Large B-Cell Lymphoma].

A man aged 65 years had undergone high orchidectomy of the right testis for diffuse large B-cell lymphoma(DLBCL) occurring primarily in the testis 11 months before. Although he was referred to another hospital for postoperative chemotherapy, he refused the treatment by self-judgement. For 1 month, he had been experiencing melena and anal pain, so he visited our department in June. Rectal palpation revealed a sub-circumference tumor palpable from the anal margin, in which a part protruded outside the anus. CT revealed a sub-circumference hypertrophic wall from the rectal Ra to the anus and intramural enlarged lymph nodes, without metastases to the other organs. Systemic gallium scintigraphy detected a strong concentration in the rectum. The endoscopic examination of the inferior region revealed a circumference type 2 tumor at Rb, and biopsy revealed DLBCL. Clinically, this case was considered a testoid DLBCL with rectal metastasis. Therefore, we performed laparoscopic rectal amputation in July, XX. sT3N1b, cM0. The postoperative course was uneventful. After the patient was discharged from our department, he received chemotherapy at another hospital. At present, 4 years 0 month postoperatively, the patient condition is favorable without recurrence. When perforation occurs in gastrointestinal DLBCL, the start of chemotherapy is delayed and the primary lesion worsen. Therefore, we performed surgical therapy first. Such cases must be evaluated for metastases or new lesions carefully.

[A Case of Sigmoid Colon Neuroendocrine Cell Carcinoma Discovered by Defecation Disorder].

A 65-year-old man presented to our hospital with a chief complaint of abdominal pain during defecation. Abdominal contrast-enhanced CT showed circumferential wall thickening with contrast effects in the sigmoid colon, and multiple metastases in the liver. Colonoscopy revealed a type 2 colon tumor that was obstructing the passage. A diagnosis of sigmoid colon cancer and multiple liver metastases was made based on laparoscopic sigmoidectomy plus D3 dissection. Pathologically, the resected specimen was diagnosed as colorectal neuroendocrine cell carcinoma(NEC)that was positive for synaptophysin and CD56. Postoperatively, 8 courses of FOLFOX plus bevacizumab(BV)therapy were administered, but CT showed remarkable increase in liver metastasis, and he died 5 months after the operation. Colorectal NEC is a very rare disease, for which no chemotherapy has been shown to be effective. Since we encounterd a case of sigmoid colon NEC with multiple liver metastases that followed a rapid course, we have presented it along with a literature review.

[A Case of Local Remnant Esophageal Cancer after Chemotherapy Getting Complete Response by Radiotherapy].

This is a case of a 72-year-old woman who presented without anymajor complaint. An anemia was indicated during follow-up for diabetes at the internal medicine unit and an upper gastrointestinal endoscopy(GS)was performed. A type 2 tumor was detected in the middle thoracic esophagus and biopsyrevealed a squamous cell carcinoma. A tumor was detected in the middle thoracic esophagus bycervical thoracoabdominal computed tomography(CT)scan and no invasion of surrounding organs was noted. The lymph node 104R had enlarged significantlybut no distant metastasis was observed. The patient was diagnosed with advanced esophageal cancer, Mt, type 2, cT2N2M0, stage Ⅱ. For preoperative chemotherapy, CDDP plus 5-FU(FP)therapywas administered. Lung metastasis was found on CT examination and surgical resection was not indicated. Hence, 4 courses of docetaxel plus CDDP plus 5-FU(DCF)therapywere administered. Following treatment, lung and lymph node metastases disappeared on the image. However, the main tumor remained at the GS. Radiotherapy was administered as a local additional treatment. Thereafter, GS showed mucous membrane redness and white spots of the lesion. Biopsyfrom the same site showed no malignant findings. The patient has remained malignancy-free since 18 months.

[A Case of Diverticular Perforation of Sigmoid Colostomy during FOLFIRI plus BevacizumabTreatment].

A 61-year-old man with a diagnosis of rectal cancer underwent assisted laparoscopic rectal amputation. Recurrence occurred, and treatment with FOLFIRI plus bevacizumab was initiated at our department. After 12 treatment courses, he developed abdominal pain at home. Emergency surgery was performed for the stoma perforation. We confirmed the diverticular perforation in the resected specimen. In our case, we found a para-stoma hernia and considered it to be the cause of perforation together with bevacizumab administration. Molecular-targeted drugs contribute to improving treatment outcomes in malignant tumors, but specific adverse events such as perforation have been reported. In addition, as causes of sigmoid colon perforation such as that of the stoma, cases associated with intestinal operation, constipation, and para-stoma hernia are suggested. In our case of hyperpolarization due to a para-stoma hernia, administration of bevacizumab was considered the cause of the perforation. This was a case that could be rescued with surgery.

[A Case of T4 Esophageal Cancer with Refractory Chylothorax Developed Postoperatively].

A 65-year-old man was diagnosed as having middle thoracic esophageal cancer(c-T3N2M0, stage III ), and neoadjuvant chemoradiotherapy was performed.We performed surgical therapy.However, tumor and #113 lymph node invasion into the aortic arch was observed; therefore, it was judged that curative resection was difficult, and R2 surgery was performed instead. Postoperative diagnosis was Mt, CRT-type 5b, s-T4(aortic arch)N4(#113)M0, stage IV a.After surgery, pleural effusion was abundant and was diagnosed as chylothorax.Even though intestinal rest and octreotide administration were performed as a conservative treatment, chylothorax was not improved.Therefore, thoracoscopic thoracic duct ligation was performed on 8POD.After that, pleural effusion was still sustained, and pleural adhesions were performed.However, it did not prove to be effective.Furthermore, when Lipiodol lymphangiography was performed to identify the leakage site, the leakage of contrast medium was observed from the remaining lymph node.After lymphangiography twice(in total), pleural effusion disappeared, and the patient was discharged on the 75POD.In this case, we report an example in which lymph leakage disappeared due to lymphangiography for diagnostic purpose, while no improvement was observed in the lymphatic leakage from the remaining metastatic lymph node in T4 esophageal cancer with R2 surgery, nor with some treatments for chylothorax, including thoracic duct ligation.

[Efficacy of Radiation Therapy for Esophageal Cancer with Bone Metastases].

We retrospectively considered the validity of radiotherapy for patients with bone metastases from esophageal cancer. Eight patients have received radiotherapy in our hospital since 2007. The median age of the patients was 63 years, with 5 men and 3 women. Bone metastatic sites were 4 to the vertebrae, 3 to the ribs, 3 to the femur and 1 each to the humerus, ulna, and radius, respectively. All of the patients had other unresectable sites of metastasis. Radiotherapy reduced pain of 3 patients of PS 1 clearly. Median survival time from the start of radiation therapy was 50 days. When PS was relatively good, the possibility of easing pain and improving QOL was suggested by our data. There is a possibility that radiation therapy for patients with bone metastases from esophageal cancer can improve the QOL and alleviate pain.

[Evaluation of esophageal cancer treatment for patients aged over 80 years].

We examined the effectiveness of chemoradiotherapy for esophageal cancer patients aged 80 years or older, 9 of whom were treated after 2010. Treatment consisted of cisplatin 35 mg/m² (day 1 and 29) and 5-FU 350 mg/m² (days 1-4 and 29- 32) combined with 50.4 Gy radiotherapy (1.8 Gy/day, 5 days/week, days 1-42). We administered 50% of the normal dose of chemotherapy. Median survival was 387 days, and there were 6 PRs, 1 SD, and 2 PDs. The toxicities related to the chemoradiotherapy were manageable (7 patients had toxicities worse than Grade 2, of whom 6 died and 3 were alive at the time of reporting). This treatment may be effective and safe for elderly esophageal cancer patients.

Incomplete bowel obstruction caused by sigmoid colon cancer in an inguinal hernia: a case report.

BACKGROUND: Most colon cancers that develop in the intestinal tract within the inguinal hernia sac are identified by incarceration. However, treatment methods for these cases vary depending on the pathology. Cases showing perforation or abscess formation require emergency surgery for infection control, while cases with no infection generally involve oncological resection, with laparoscopic surgery also being an option. We encountered a case of Incomplete bowel obstruction secondary to sigmoid colon cancer within the hernial sac. We report the process leading to the selection of the treatment method and the surgical technique, along with a review of the literature. CASE PRESENTATION: A 79-year-old man presented to our hospital complaining of a left inguinal bulge (hernia) and pain in the same area. The patient had the hernia for more than 20 years. Using computed tomography, we diagnosed an incomplete bowel obstruction caused by a tumor of the intestinal tract within the hernial sac. Since imaging examination showed no signs of strangulation or perforation, we decided to perform elective surgery after a definitive diagnosis. After colonoscopy, we diagnosed sigmoid colon cancer with extra-serosal invasion; however, we could not insert a colorectal tube. Although we proposed sigmoid resection and temporary ileostomy, we chose the open Hartmann procedure because the patient wanted a single surgery. For the hernia, we simultaneously used the Iliopubic Tract Repair method, which does not require a mesh. Eight months after the surgery, no recurrence of cancer or hernia was observed. CONCLUSIONS: We report a case of advanced sigmoid colon cancer with a long-standing inguinal hernia that later became incomplete bowel obstruction. Although previous studies have used various approaches among the available surgical methods for cancer within the hernial sac, such as inguinal incision, laparotomy, and laparoscopic surgery, most hernias are repaired during the initial surgery using a non-mesh method. For patients with inguinal hernias that have become difficult to treat, the complications of malignancy should be taken into consideration and the treatment option should be chosen according to the pathophysiology.

Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin-6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.

[A case of primary esophageal carcinoma treated with 5-fluorouracil plus cisplatin and curatively resected after complete response].

A 76-year-old woman visited the hospital for difficulty during swallowing. Endoscopy revealed the presence of an esophageal tumor, and she was referred to our hospital for further examination. A subsequent endoscopy revealed a whole rounded type 3 tumor in the lower esophagus. Computed tomography( CT) scan showed swelling of the lymph node( number 106recL), and no remote metastasis was observed. A diagnosis of Lt type 3, T3N1M0, clinical Stage III esophageal cancer was made, and neoadjuvant chemotherapy( NAC) with 5-fluorouraci(l 5-FU) plus cisplatin( CDDP) was administered. The only side effect noted was grade 1 anorexia. Endoscopy after 2 courses of NAC revealed only scars, and no tumor was detected. CT showed remarkable reduction of the lymph nodes and esophageal wall thickness. Subtotal esophagectomy by right thoracotomy, retrosternal gastric tube reconstruction, and 3-field lymph node dissection were performed. Histopathological examination of the resected specimen revealed the absence of malignant cells in the esophagus and presence of metastasis in the lymph node (Effect 3). Although we have encountered 49 cases of esophageal cancer treated with NAC at our center, this was the first case in which pathologically complete response was achieved. Here, we report a rare case of esophageal carcinoma, which was curatively resected after complete response was achieved following treatment with 5-FU/CDDP as NAC.

Growth Differentiation Factor-15 and Clinical Outcomes in Japanese Patients With Ischemic Heart Disease.

Background: Despite a reduction in the rate of thrombotic events, ischemic heart disease (IHD) remains a key medical problem associated with high major bleeding and mortality in Asian patients with IHD. Growth differentiation factor (GDF)-15, a stress-response cytokine belonging to the transforming growth factor beta superfamily, is reportedly associated with poor clinical outcomes in Western patients with IHD. However, the clinical significance of GDF-15 in Asian patients with IHD has not yet been fully elucidated. Objectives: The aim of the present study was to examine the impact of serum GDF-15 on clinical outcomes in Japanese patients with IHD. Methods: Serum GDF-15 levels were evaluated in 632 consecutive patients with IHD. All patients were followed up for a median period of 2.8 years. The primary endpoint was the all-cause mortality rate. Secondary endpoints were major adverse cardiovascular events (MACE), heart failure (HF)-related rehospitalization, bleeding, and thrombotic events. Results: Serum GDF-15 levels were elevated in acute coronary syndrome, severe coronary artery disease, and the major Japanese version of the high bleeding risk criteria. Multivariate Cox proportional hazards regression analysis demonstrated that GDF-15 was an independent predictor of all-cause mortality, MACE, HF-related rehospitalizations, and bleeding events after adjusting for confounding risk factors but not for thrombotic events. Adding GDF-15 to risk factors significantly improved the net reclassification index and integrated discrimination improvement for all-cause deaths, MACE, HF-related rehospitalization, and bleeding events. Conclusions: Serum GDF-15 could be a feasible marker for major bleeding and adverse clinical outcomes in Japanese patients with IHD.

Renal tubular damage and clinical outcome in heart failure with preserved ejection fraction and chronic kidney disease.

AIMS: Despite advances in heart failure (HF) treatment, HF with preserved ejection fraction (HFpEF) remains a health problem with a high mortality rate. HFpEF is composed of diverse phenogroups, of which patients with concomitant renal impairment have worse outcomes. Renal tubular damage (RTD) is associated with the development of HF and chronic kidney disease (CKD). However, the impact of RTD on HF progression in patients with HFpEF and CKD remains unclear. The aim of the present study was to examine whether RTD could predict HF-related events in patients with HFpEF and CKD. METHODS AND RESULTS: We measured RTD markers, such as urinary ß2 -microglobulin to creatinine ratio (UBCR) and N-acetyl-ß-d-glucosamidase (NAG) level, in 319 consecutive patients with HFpEF and CKD who were hospitalized for acute HF (49% females, mean age 76 ± 12). Based on previous reports, high UBCR and high NAG levels were defined as UBCR ≥300 µg/gCr and NAG >14.2 U/gCr, respectively. There were 91 HF-related events, defined as HF hospitalizations or HF deaths, during the median follow-up period of 5.2 years. The prevalence of high UBCR increased with advancing New York Heart Association functional class and albuminuria. Kaplan-Meier analysis demonstrated that patients with high UBCR had more HF-related events than those with normal or low UBCR. Multivariate Cox proportional hazards regression analyses demonstrated that high UBCR, but not high NAG level, was an independent predictor of HF-related events after adjusting for confounding risk factors in patients with HFpEF and CKD (hazard ratio, 2.60; 95% confidence interval, 1.52-4.72; P = 0.0009). UBCR significantly improved the C-statistic, with a significant net reclassification index and integrated discrimination improvement (0.738 vs. 0.684; P = 0.0244). CONCLUSION: RTD, as assessed by a high UBCR, was associated with the severity and clinical outcomes of HFpEF and CKD, indicating that it could be a feasible marker for HF progression.

Activity of daily life dependency predicts the risk of mortality in patients with COVID-19 undergoing hemodialysis: a retrospective analysis of a single center with nosocomial outbreak.

Background: We experienced a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from November 2020 to February 2021, during the third wave of the pandemic in Japan. Methods: We retrospectively assessed the characteristics and data of 20 inpatients undergoing hemodialysis who were hospitalized for treatment of diseases other than COVID-19 during the COVID-19 nosocomial outbreak ("inpatient," IP), and of 10 outpatients undergoing hemodialysis who were hospitalized for the care of COVID-19 under outpatient visits ("outpatient," OP). Results: Eleven patients in the IP group (55%) and one in the OP group (10%) died. Kaplan-Meier analysis showed that the IP group died more rapidly than the OP group (p = 0.02). Multivariate analysis among all hemodialysis patients showed that the IP group was not at risk of mortality independently; however, the activity of daily life (ADL) dependency was found to be an independent factor in increasing the risk of mortality (hazard ratio: 7.618). Conclusion: Our findings show that the nosocomial infected group has a worse prognosis, although it is not an independent predictor for the risk of mortality. ADL dependency could predict the risk of mortality in all hemodialysis patients with COVID-19 during the third wave pandemic in Japan.

Association of malnutrition with renal dysfunction and clinical outcome in patients with heart failure.

Malnutrition, glomerular damage (GD), and renal tubular damage (RTD) are common morbidities associated with poor clinical outcomes in heart failure (HF) patients. However, the association between malnutrition and renal dysfunction and its impact on clinical outcomes in HF patients have not yet been fully elucidated. We assessed the nutritional status and renal function of 1061 consecutive HF patients. Malnutrition, GD, and RTD were defined as a controlling nutritional status (CONUT) score of ≥ 5, reduced eGFR or microalbuminuria, and levels of N-acetyl-beta-D-glucosamidase of > 14.2 U/gCr according to previous reports, respectively. Patients with RTD had a higher CONUT score and a lower prognostic nutritional index and geriatric nutritional risk index than those without. Multivariate logistic analysis demonstrated that RTD, but not GD, was significantly associated with malnutrition. There were 360 cardiac events during the median follow-up period of 688 days. Multivariate Cox proportional hazard regression analysis demonstrated that comorbid malnutrition and renal dysfunction, rather than simple malnutrition, were significantly associated with cardiac events in HF patients. We found a close relationship between malnutrition and renal dysfunction in HF patients. Comorbid malnutrition and renal dysfunction were risk factors for cardiac events in HF patients, suggesting the importance of managing and treating these.

Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.

UNLABELLED: We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice. However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations. By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI). The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis. CONCLUSION: IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol. The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair.