Endoscopic ultrasound-guided fine-needle aspiration of enlarged adrenals in patients with pyrexia of unknown origin: A single-center experience of 52 cases

Background

Fine-needle aspiration (FNA) of adrenals is needed in patients with pyrexia of unknown origin (PUO) and adrenal enlargement in absence of other diagnostic clues. Adrenals are easily accessible by endoscopic ultrasound (EUS) due to proximity; however, there is no systemic study available on FNA of adrenals in patients with PUO. The aim of this study was to evaluate the diagnostic yield and safety of EUS-FNA of enlarged adrenal in patients with PUO.

Methods

Data was analyzed from October 2010 to September 2016 at a single tertiary care center in northern India. EUS-FNA of enlarged adrenals was done in 52 patients for the etiological diagnosis of PUO in whom a definitive diagnosis could not be made with other means.

Results

The mean age was 48±14 years; 36 were males and 16 were females. EUS-FNA was done from the left adrenal in 50 patients and from the right sample in 2 patients. A technical success was achieved in 100% cases. The 19-G needle was used in the majority (75%) to the presence of necrotic areas in adrenals; median numbers of passes were 2. The cytopathological diagnoses were tuberculosis (n?=?36), histoplasmosis (n?=?13), lymphoma (n?=?2), and metastasis from undiagnosed neuroendocrine tumor of lung (n?=?1). Thus, a diagnosis could be made in 52/52 (100%) patients. None of the patients had any procedure-related complications.

Conclusions

EUS-FNA is a safe and effective method for evaluating etiology of PUO in patients with adrenal enlargement.

     

Lipoprotein(a) as an independent risk factor for coronary artery disease in patients below 40 years of age

Coronary artery disease has assumed alarming proportions in Indians and often affects people at younger age. Traditional risk factors fail to explain the high incidence of disease. Although lipoprotein(a) has been shown to be a powerful risk factor for atherosclerosis, there is very limited data with regard to its significance in premature coronary artery disease. The present study was therefore undertaken to assess lipoprotein(a) levels and its role as a marker of coronary artery disease in patients below the age of 40 years. Lipid profile and lipoprotein(a) levels were estimated in 50 patients of angiographically proven coronary artery disease and an equal number of age-matched healthy controls. There was no significant difference in the family history of coronary artery disease, body mass index and waist-hip ratio between the two groups. Total plasma cholesterol, triglyceride and LDL-cholesterol levels were significantly higher and HDL-cholesterol significantly lower in patients as compared to controls. In patients of coronary artery disease, mean lipoprotein(a) levels, measured by ELISA method, were 35.0 +/- 32.4 mg/dL and the median was 26.7 mg/dL. These values were significantly higher than the mean of 20.3 +/- 17.0 mg/dL (p < 0.002) and the median of 13.8 mg/dL (p < 0.015) in controls. Multiple regression analysis, to assess the influence of various risk factors, showed that low HDL-cholesterol (odds ratio 4.62, 95% CI 1.84-11.60; p < 0.015) and elevated lipoprotein(a) levels (odds ratio 3.06, 95% CI 1.24-7.55; p < 0.001) were independent risk factors, whereas high total cholesterol and triglyceride levels did not have any independent influence on premature coronary artery disease. Our data thus suggest that lipoprotein (a) levels are elevated and constitute an independent risk factor in patients with premature coronary artery disease below 40 years of age.     

Epidemiological profile,management and outcomes of patients with acute coronary syndrome: Single centre experience from a tertiary care hospital in North India

BackgroundCardiovascular disease is the leading cause of death in India. Our aim is to study the clinical, epidemiological profile and in-hospital outcomes of patients presenting with acute coronary syndrome.MethodsWe did a prospective single center observational study of the 1203 patients presenting with ACS to a tertiary referral center in North India over a period of one year (July 2018–June 2019).ResultsThe mean age of study population was 58.4 ± 12.5 years. STEMI and NSTE-ACS accounted for 69.9% and 31.1% respectively. 62.1% of our patients were from rural background. The median time to hospital admission was 600 min for STEMI patients, thrombolysis was performed in 52% of cases. Cardiogenic shock at presentation was noted in 18%. Coronary angiography and percutaneous coronary intervention were done in 1062 (88.3%) and 733 (60.9%) patients respectively. The overall in-hospital mortality was 7.6%. STEMI patients had higher mortality than NSTE-ACS (8.9% vs 4.5% p < 0.001). Female gender (OR?3.306 C.I. 1.87–5.845), severe MR (OR?4.65, C.I.?1.187–18.18), acute kidney injury (AKI) at admission (OR-5.15, C.I.?2.5–10.63), higher Killip class (class III/IV) (OR?3.378,C.I.?1.292–8.849), AF (OR?3.25, C.I.?1,18–8.92), complete heart block (CHB) (OR?4.44,C.I.?2.09–9.43) and right bundle branch block (RBBB) (OR?2.86, C.I.?1.2–6.8) were significant predictors of in hospital mortality.ConclusionsOur study represents the predominance of STEMI as the initial ACS presentation with a considerable delay in first medical contact and higher prevalence of cardiogenic shock (CS). STEMI patients had higher mortality. Female sex, severe MR, AKI, higher Killips class, AF, CHB, RBBB being predictors of high in-hospital mortality in ACS patients.     

Treatment strategies for central nervous system infections: an update

Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.

Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.

Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.     

Applications of In Vitro–In Vivo Correlations in Generic Drug Development: Case Studies

In vitro–in vivo correlation (IVIVC) is a predictive mathematical model describing the relationship between an in vitro property and a relevant in vivo response. The main objective of an IVIVC is to serve as a surrogate for human bioequivalence (BE) studies, which may reduce the number of BE studies performed during the initial approval process as well as with certain scale-up and postapproval changes. The US Food and Drug Administration (FDA) published a regulatory guidance related to development, evaluation, and applications of IVIVC for extended-release (ER) oral dosage forms in September 1997. Despite the publication of this guidance, the deficiencies related to IVIVC are still identified by the Division of Bioequivalence in the process of Abbreviated New Drug Application (ANDA) review. Thus, the main objective of this article is to present the most commonly occurring deficiencies associated with IVIVCs via selected case studies from the ANDAs for oral ER drug products only. We searched internal FDA databases from January 1996 to December 2014 to identify the ANDAs for proposed generic oral ER drug products containing IVIVC. Only 14 ANDA submissions had IVIVC data, and most were not acceptable. Only one ANDA submission included adequate information related to IVIVC data enabling the completion of BE review within first review cycle. It is hoped that awareness of the deficiencies presented in our article would help the generic drug applicants to submit complete and appropriate information related to IVIVC data, ultimately, resulting in a more timely approval of ANDAs.KEY WORDS: bioequivalence, extended-release drug products, generics, IVIVC, SUPAC     

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression.     

Pure neuritic leprosy in India: an appraisal

BACKGROUND: Pure neuritic leprosy (PNL) constitutes a significant proportion of all cases in India, however, this form of disease has not been fully recognized and investigated and there is little information in the existing literature. OBJECTIVE: To study the epidemiological characteristics of PNL in India. MATERIALS AND METHODS: A retrospective analysis of leprosy clinic records for the period 1993 to 2003 was undertaken. Detailed demographic profiles and clinical findings were noted from the predesigned clinic proforma. A slit-skin smear for acid-fast baclli (AFB) was done in all cases from the area of sensory loss. A skin biopsy was done from the area of sensory impairment to study histopathological changes. Further investigations such as nerve conduction velocity studies (NCV), fine needle aspiration cytology (FNAC), or nerve biopsy (superficial nerve twigs) were done if indicated in patients whenever there was difficulty in clinical diagnosis. RESULTS: Of the total 1542 leprosy patients seen over this period, 65 (4.2%) had PNL. Males were more commonly affected than females (2.6:1.). The majority of patients 40/65(61.5%) were aged between 15 and 35 yrs. Predominant presenting symptoms were paresthesia, pain, sensory/motor deficit, and trophic changes. A majority of the patients 39/65 (60.0%) presented with involvement of 2 or more nerves in the same extremity. Mononeuritis was seen in 26 (40%) patients. The nerves most often involved were the right ulnar nerve in the upper extremity, and the right common peroneal nerve in the lower limb. In general, the nerves of the upper extremity were more commonly involved than in the lower limbs (67 vs. 55). Motor deformities such as claw hand and foot drop were present in 13/75 (20%) and 7/65 (10.8%) patients, respectively. Slit-skin smears were negative in all patients, and skin histopathology from the area of sensory loss revealed non-specific inflammation in the dermis in a majority of patients, with perineural inflammation in a few. All patients were treated with multi-drug therapy (MDT); patients with >/=2 peripheral nerve trunk involvements were treated with WHO MDT MB regimen, while others were administered WHO MDT PB regimen. Follow-up for up to 2 yrs was available in only 32/65 (49.2%) patients, none of whom developed any skin lesions during this period. CONCLUSION: PNL is a distinct subset of disease frequently seen in India. There is need to pay more attention to this form of leprosy and diagnose and treat patients earlier to prevent deformities and sequelae of nerve damage.