Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Chronic Progressive Autonomic Dysfunction in a Dog

A 3.5‐year‐old intact male American Pit Bull was presented because of urinary incontinence and dysuria. Constipation, followed by diarrhoea, ocular disturbances and finally regurgitation developed over the next 4 years. Autonomic dysfunction was evidenced by clinical presentation, as well as positive ophthalmic pilocarpine test and subnormal Schirmer tear test. Diagnosis, however, was established through histopathological and immunohistochemical examination. Lesions attributable to inflammatory degenerative neuropathy of the autonomic ganglia, which represents one of the various types of human autonomic failure, were detected.     

epsilon factor of representations of classical groups

We let G be the isometry group of a nondegenerate symmetric or skew-symmetric form h on a space V over some local or global field K [i.e., G = U(V, h)]. We let (L)G be the L group of G(o) = the identity component of G and r be the natural representation of this group. We develop here a theory of L functions and epsilon factors attached to this r. In particular we develop a theory of local and global zeta integrals for such G. We use very special intertwining operators; therein we require an analysis of the proper normalization of such operators. With such techniques we determine the correct epsilon factors associated to local representations. The issue of the correct local L factor is discussed.     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

CLINICO-PATHOLOGICAL CORRELATION IN NEONATAL AUTOPSIES

Of the 253 neonates admitted to a neonate intensive care unit during the period Jan 91 to Sep 93, 43 neonates died. Autopsy was done in 23 of these (53%). The mean duration of stay of the neonates in the intensive care unit prior to death was 5.6 days (range 2 hours to 10 days). Antemortem diagnoses included asphyxia neonatorum (4), meconium aspiration syndrome (2), septicemia (5), prematurity (3), birth trauma (2), congenital anomalies (2), hypoxic ischemic encephalopathy (1), and non-specific diagnosis (4). There were 6 major autopsy findings that, if known prior to death, would have altered clinical management and might have resulted in cure or prolonged survival. There were 8 additional major findings that, if known prior to death, would not have altered management There were 14 minor findings related to major diagnoses but unrelated to the primary cause of death.KEY WORDS: Autopsy, Cause of death, Perinatal mortality     

Thyroid function in a population of children with attention deficit hyperactivity disorder

To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated.

Method:

Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed.

Results:

The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%.

Conclusion:

Routine thyroid hormone screening is not indicated in children with non-familial ADHD.     

Immunotherapy for advanced hepatocellular carcinoma: From clinical trials to real-world data and future advances

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers. Advanced HCC is managed with systemic therapies; the tyrosine kinase inhibitor (TKI) sorafenib has been used in 1^st-line setting since 2007. Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors (ICIs) are licensed in 1^st- and 2^nd-line treatment setting. The treatment field of advanced HCC is continuously evolving. Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents, such as other ICIs, TKIs, and anti-angiogenics. Novel immunotherapies including adoptive cell transfer, vaccine-based approaches, and virotherapy are also being brought to the fore. Yet, despite advances, several challenges persist. Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort. Consequently, issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications, comorbidities, or poor performance status; lack of response, efficacy, and safety data; and cost-effectiveness. Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making. This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC, with a focus on ICIs, as well as novel immunotherapy strategies underway.