Therapy-related acute myeloid leukemia following postoperative adjuvant chemotherapy including cisplatin and fluorouracil for esophageal carcinoma

We report a case of therapy-related acute myeloid leukemia (t-AML), which developed following chemotherapy involving cisplatin and 5-fluorouracil for esophageal carcinoma. A 70-year-old man with past history of esophageal carcinoma, which was treated with subtotal esophagectomy 32 months earlier followed by 2 courses of chemotherapy involving cisplatin and 5-fluorouracil, was diagnosed with t-AML. His leukemia was resistant to chemotherapy, and the patient died from pneumonia 4 months after being diagnosed with leukemia. Although treatment for esophageal carcinoma is associated with a markedly lower frequency of therapy-related myeloid neoplasms than treatment for certain other malignancies such as hematological neoplasms, it is important to be aware that therapy-related myeloid neoplasms can occur as late complications of esophageal carcinoma treatment.     

Calcium and calcimimetics regulate paracellular Na+ transport in the thin ascending limb of Henle’s loop in mouse kidney

The effect of Ca²⁺ and calcimimetics on NaCl transport was investigated in the in vitro isolated microperfused mouse thin ascending limb of Henle’s loop. In the presence of a transmural NaCl gradient, the transepithelial diffusional potential was 13.7?±?0.4 mV (n?=?17). When the Ca²⁺ in the bath was increased from 1.5 to 4.5 mM at 37°C, the relative permeability of Na⁺ to Cl^? (P _Na /P _Cl) estimated from the diffusional voltage deflection due to the transepithelial NaCl gradient (V _d) changed from 0.371?±?0.017 to 0.341?±?0.015 (n?=?10, P?<?0.0001). When the Ca²⁺ in the lumen was increased from 1.5 to 4.5 mM, the P _Na /P _Cl decreased from 0.349?±?0.013 to 0.330?±?0.013 (n?=?5, P?<?0.002). The addition of 0.1 mM neomycin and 0.2 mM gentamicin to the bath or lumen also decreased the P _Na /P _Cl. The same effect on P _Na /P _Cl of Ca²⁺ and calcimimetics occurred in ClC-K1 (kidney-specific chloride channel) knockout mice. The addition of 300 μg/ml protamine to the bath strongly inhibited changes to P _Na /P _Cl induced by basolateral Ca²⁺. These data indicate that ambient Ca²⁺ and calcimimetics inhibit Na⁺ transport in the thin ascending limb, which is known to occur via the paracellular shunt pathway. Our observations strongly suggest that Ca²⁺ is involved in the regulation of paracellular Na⁺ permeability in the thin ascending limbs.     

Significance of a positive Clostridium difficile toxin test after hematopoietic stem cell transplantation

Patients with hematological malignancies show a high prevalence of asymptomatic colonization with Clostridium difficile (CD colonization). Therefore, it is difficult to distinguish CD colonization with diarrhea induced by a conditioning regimen from true Clostridium difficile infection (CDI) in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively analyzed 308 consecutive patients who underwent a CD toxin A/B enzyme immunoassay test for diarrhea within 100 d after HSCT from November 2007 to May 2014. Thirty patients (9.7%) had positive CD toxin results, and 11 of these had positive results in subsequent tests after an initial negative result. Allogeneic HSCT, total body irradiation, stem cell source, acute leukemia, and the duration of neutropenia were significantly correlated with positive CD toxin results. In a logistic regression model, allogeneic HSCT was identified as a significant risk factor (odds ratio 18.6, p < 0.01). In an analysis limited to within 30 d after the conditioning regimen, the duration of neutropenia was the sole risk factor (odds ratio 10.4, p < 0.01). There were no distinctive clinical features for CDI, including the onset or duration of diarrhea. In conclusion, although CDI may be overdiagnosed in HSCT recipients, it is difficult to clinically distinguish between CDI and CD colonization.     

Multicentric papillary and follicular carcinomas of the thyroid

A 63-year-old female, complaining of a swelling in the neck, was diagnosed as having a thyroid carcinoma. Thus, a subtotal thyroidectomy was performed, leaving a part of the right lobe. Two thyroid carcinomas were found in the left lobe, and one carcinoma in the right lobe with a right cervical lymph nodal involvement. Each carcinoma was small and encapsulated by thick fibrous tissue, but there was no continuity among them. The three carcinomas were regarded as being multicentric in origin, and not an intraglandular metastasis.     

Carbonic anhydrases in the human adrenal gland and its disorders: Immunohistochemical and biochemical studies of the enzymes

To study the possible roles of carbonic anhydrases (CA) in the human adrenal glands, an immunohistochemical study (using polycloncal antibodies against CA I and II), and a biochemical assay of CA activity (based on the change in pH caused by the hydration of CO₂) were performed in normal human adrenal tissue and adrenocortical adenomas. All of 10 normal adrenal glands showed positive staining for CA II in the zona glomerulosa, whereas weak CA I-positive staining was detected in only 5 glands. A biochemical study of 3 normal human adrenal specimens also demonstrated CA activity only in the outer adrenal cortex. Of 26 adrenocortical adenoma specimens ( 15 aldosteronomas, 6 nonfunctioning adenomas, and 5 Cushing’s adenomas), CA I and II immunoreactivity was observed in only 3 and 5 aldosteronoma samples, respectively. A biochemical analysis of CA in 5 adenoma specimens (3 aldosteronomas, 2 nonfunctioning adenomas) detected enzymatic activity in 2 aldosteronomas. In all 26 specimens of non-neoplastic attached adrenals of adrenocortical adenomas, CA II immunoreactivity was present in the zona glomerulosa cells. These results indicate that CAs are present in the zona glomerulosa cells of the non-neoplastic human adrenals glands (but not in the majority of adrenocortical adenomas) and that CA II may constitute the major form of the enzyme. Exclusive localization of CA II in the zona glomerulosa cells in human adrenal glands may suggest a possible involvement of CAs in aldosterone biosynthesis or secretion through ion transport, or both. Our data also suggest that CA II can be used as an immunochemical marker for the zona glomerulosa cells in human adrenal glands.     

Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung

The expression of matrix mdalloproteinase-2 (MMP-2; 72 kDa type IV collagenase/gelatinase A) and MMP-9 (92 kDa type IV collagenase/gelatinase B) was Immunohisto chemically Investigated In 79 T1 adenocarcinomas of the lung using non-commerclal polydonal anti-MMP-2 and -9 antibodies. Thirty-two (41%) and 22 (28%) among the 79 cases were positive in the tumor cells for MMP-2 and -9, respectively. The incidences of MMP-2 and -9 Immunoreactivities were higher (64 and 45%, respectively) in poorly differentiated tumors than in well differentiated tumors (36 and 25%, respectively), and lower in bronchloloalveolar carcinoma (22 and 10%, respectively) compared with other subtypes of adenocarcinoma. The prognosis for patients with MMP-2 andor -9 positive Immunoreactivities was significantly poorer than for those with a MMP-negative tumor (P<0.05). The degree of collagenization was divided into four grades, and tumors with a small to abundant amount of collagen (grade 2 and grade 3 fibrosis) had a higher Incidence of Immunoreactivity to both types of MMP. It is estimated that these expressions might be responsible for tumor Invasion, metastasis, and for grade 2 and grade 3 fibrosis In T1 adenocarcinoma of the lung.     

Impact of the HeartMate 3 continuous-flow left ventricular assist device in patients with small body size

Open in a separate window OBJECTIVESLimited data are available for use of the HeartMate 3 (HM 3) left ventricular assist device in patients with a small body surface area (BSA). Because the HM 3 is currently the sole device available worldwide, we conducted a single-centre retrospective study of patients with a small BSA (<1.5 m²) who underwent HM 3 implantation to better understand the operative and postoperative management.METHODSThis study enrolled 64 consecutive patients who had undergone HM 3 implantation from August 2018 to July 2021. The patients were divided into 2 groups based on their BSA before the operation: BSA of <1.5 m² (small BSA group, n = 18) and BSA of ≥1.5 m² (regular BSA group, n = 46). The primary study endpoint was survival free of events such as disabling stroke and pump failure. The secondary endpoint was the frequency of adverse events.RESULTSThe average BSA was 1.38 m² in the small BSA group. The overall event-free survival rate at 12 months was 100% and 86.7% in the small BSA group and regular BSA group, respectively, and no significant difference was found between the 2 groups (log-rank P = 0.2). The number of cumulative adverse events of death, stroke of any severity, driveline infection, pump infection, ventricular arrhythmia, gastrointestinal Haemorrhage and pump failure was similar between the 2 groups.CONCLUSIONSThe HM 3 was safely implanted in patients with a small BSA, and postoperative outcomes were acceptable regardless of BSA. However, further research is needed to confirm the indications for HM 3 implantation in even smaller patients.     

Understanding clinical risk decision making regarding development of depression during interferon-alpha treatment for hepatitis-C: A qualitative interview study

BackgroundHepatitis C virus (HCV) affects 170 million worldwide. Currently, around 30% of patients receiving interferon-alpha (IFN-α) treatment for HCV experience clinically significant depression. Effective and timely detection of depression is crucial to ensuring appropriate treatment and support. However, little is known about how clinical nurse specialists identify patients at risk of developing interferon-alpha-induced depression, and monitor those receiving antiviral treatment for the occurrence of depression.ObjectiveThis study aimed to gain an in-depth understanding of staff experience of, and attitudes towards, the identification and monitoring of interferon-alpha-induced-depression and the decision-making process concerning the use of liaison psychiatry and other clinical services.DesignA qualitative interview study was conducted among clinical staff involved in the care of patients with hepatitis C, using the perspective of naturalistic decision making.SettingsOutpatient liver clinics in three large teaching hospitals in South London, the United Kingdom.ParticipantsAll clinical nurse specialists from the three outpatient liver clinics were included. All were involved directly in the care of patients receiving interferon-alpha treatment and had at least one year experience (mean 6.4 years, range 1–11 years) in this field.MethodsSemi-structured face-to-face interviews were conducted between 2010 and 2011. Data collection and analysis were carried out iteratively to ensure the reliability of the analysis using the constant comparison method.ResultsStaff used verbal and non-verbal cues when assessing risks of patients developing depression before and during IFN-α treatment. Major sources of uncertainty were patient engagement and familiarity, referrals to psychiatrists, language barriers, and distinguishing between psychological and physical symptoms. Good rapport with patients and good communication among multidisciplinary professional groups were key strategies identified to reduce uncertainty.ConclusionCurrent methods of identifying vulnerable patients rely on the availability of clinical experts and good communication within a multidisciplinary team. Detection and management of depression in this population is complex, however, various strategies are employed by nurses to overcome difficulties when making decisions regarding patient welfare. Current clinical practices should be taken into account when developing new tools and methods.     

Serum salusin-alpha levels are decreased and correlated negatively with carotid atherosclerosis in essential hypertensive patients.

Salusin-alpha is a new bioactive peptide with mild hypotensive and bradycardic effects. Our recent study showed that salusin-alpha suppresses foam cell formation in human monocyte-derived macrophages by down-regulating acyl-CoA:cholesterol acyltransferase-1, contributing to its anti-atherosclerotic effect. To clarify the clinical implications of salusin-alpha in hypertension and its complications, we examined the relationship between serum salusin-alpha levels and carotid atherosclerosis in hypertensive patients. The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure, serum levels of salusin-alpha, and atherosclerotic parameters were determined in 70 patients with essential hypertension and in 20 normotensive controls. There were no significant differences in age, gender, body mass index, fasting plasma glucose level, or serum levels of high-sensitive C-reactive protein, high- or low-density lipoprotein (LDL) cholesterol, small dense LDL, triglycerides, lipoprotein(a), or insulin between the two groups. Serum salusin-alpha levels were significantly lower in hypertensive patients than in normotensive controls. The plasma urotensin-II level, maximal IMT, plaque score, systolic and diastolic blood pressure, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than in normotensive controls. In all subjects, maximal IMT was significantly correlated with age, systolic blood pressure, LDL cholesterol, urotensin-II, salusin-alpha, and HOMA-IR. Forward stepwise multiple linear regression analysis revealed that salusin-alpha levels had a significantly independent and negative association with maximal IMT. Serum salusin-alpha levels were significantly lower in accordance with the severity of plaque score. Our results suggest that the decrease in serum salusin-alpha, an anti-atherogenic peptide, may be associated with carotid atherosclerosis in hypertensive patients.