The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement

Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril–Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril–Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril–Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril–Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40–50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

A rare case of bilateral choroidal coloboma within deep posterior staphyloma associated with macular hole retinal detachment

To report case of bilaterally symmetrical choroidal coloboma within posterior staphyloma with MHRD. This is a case report of a 50year old female presented with diminished vision in both eyes. On examination, she had Bilateral High Myopia with recent onset MHRD associated with symmetrically bilateral Choroidal Coloboma within posterior staphyloma and was operated for MHRD in left eye. Presence of choroidal coloboma within posterior staphyloma is rare and with coexisting macular hole makes pathophysiology of RD challenging to understand.

Distribution of Chlamydia trachomatis omp A genotypes in patients attending a sexually transmitted disease outpatient clinic in New Delhi, India

Background & objectives: Limited data are available on the typing of Chlamydia trachomatis in India. Serovars D to K of C. trachomatis are chiefly responsible for urogenital infections. Thus, this study was conducted to determine the distribution of C. trachomatis serovars in patients with urogenital infections and to characterize omp A gene of the detected C. trachomatis isolates by sequence analysis. Presence of other co-infections was also evaluated. Methods: Endocervical swabs were collected from 324 women and urethral swabs/urine were collected from 193 men attending the sexually transmitted diseases outpatient clinic. The samples were screened for C. trachomatis by cryptic plasmid PCR and omp A gene PCR. Genotyping was performed by PCR-restriction fragment length polymorphism (RFLP) and sequencing of the omp A gene. Samples were screened for genital mycoplasmas, Neisseria gonorrhoeae, Treponema pallidum and human immunodeficiency virus (HIV). Results: C. trachomatis was found in 15.0 per cent men and 10.8 per cent women. Serovar D was the most prevalent followed by serovars E, F, I and G. Twenty two C. trachomatis isolates were selected for omp A gene sequencing. No mixed infection was found. Variability in omp A sequences was seen in 31.8 per cent cases. Both PCR-RFLP and omp A gene sequencing showed concordant results. The presence of Ureaplasma spp. and Mycoplasma hominis was observed in 18.7 and 9.5 per cent patients, respectively. Co-infection of C. trachomatis was significantly associated with Ureaplasma urealyticum and HIV. Interpretation & conclusions: The high occurence of C. trachomatis infections warrants its screening in addition to other sexually transmitted infections namely U. urealyticum and HIV. Genotyping of the omp A gene may provide additional information for vaccine development.

Herpes simplex virus type 2 and cytomegalovirus perigenital ulcer in an HIV infected woman

We report a case of mucocutaneous Herpes Simplex Virus (HSV)-2 and Cytomegalovirus (CMV) infection in a 39-year-old female with acquired immunodeficiency syndrome, who presented with a perigenital ulcer. The patient was receiving antiretroviral treatment (ART) for 3 months before presentation. Scraping from the perigenital ulcer was positive for HSV-2 and Treponema pallidum using polymerase chain reactions (PCR). The extent and duration of the lesions led us to consider the possibility of coinfection with CMV. The patient also tested positive for CMV by PCR. On subsequent follow-up after 8 weeks, the genital lesions had healed completely. This is possibly ascribable to the ART, which led to significant immune reconstitution.

Applicability of 2008 World Health Organization classification system of hematolymphoid neoplasms: Learning experiences

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.

A non-inferiority randomized controlled clinical trial comparing Unani formulation & psoralen plus ultraviolet A sol in chronic plaque psoriasis

Background & objectives: Though Unani medications have been used for centuries to treat psoriasis, there is paucity of published studies which have systematically evaluated their efficacy and safety. This study was conducted to establish non-inferiority of Unani medications (oral UNIM-401 and topical UNIM-403) vs psoralen plus ultraviolet A (PUVA) sol in treatment of moderate-severe chronic plaque psoriasis (CPP) in achieving psoriasis area severity index (PASI) 75 at 12 wk and to estimate proportion of patients who relapsed in follow up period of 12 weeks, after having achieved PASI 50. Methods: In this randomized, controlled trial patients with CPP were block randomized to receive either Unani treatment (147 patients) or PUVA sol (140 patients) for 12 weeks. Percentage reduction in PASI was determined in each patient at 12 wk to calculate number of patients who achieved PASI 75 as also to estimate median of percentage reduction in PASI in each group. All patients who achieved PASI 50 at 12 weeks were followed up for another 12 wk to determine proportion of patients who relapsed. Results: Of the 287 patients randomized, 84 of 147 in Unani group and 67 of 140 in PUVA sol group completed 12 weeks of treatment. On intention-to-treat (ITT) analysis, the response in patients on Unani medication was not inferior to those receiving PUVA sol, in attaining PASI 75 (16.3% in Unani group vs 15.7% in the PUVA sol group). Median of percentage reduction of PASI at 12 wk from baseline in Unani group (68.2%; ?60, 100) and PUVA sol group (63%; ?15.7, 100) was comparable. Proportion of patients who relapsed at 24 wk was comparable in both groups. However, frequency of clinical side effects was significantly higher (P =0.001) in PUVA sol group (16.4%) compared to Unani group (2%). Interpretation & conclusions: The findings of the present study indicated that oral UNIM-401 and topical UNIM-403 were effective and well tolerated therapeutic options in patients with moderate-severe CPP.

Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain / Los abridores de canales de potasio exhiben tolerancia cruzada con la morfina en dos modelos experimentales de dolor

OBJECTIVE: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. METHODS: Swiss albino mice of either gender weighing between 25-30 g were used for the study. The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. RESULTS: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. CONCLUSIONS: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.

OBJETIVO: El estudio fue realizado para evaluar el efecto de los abridores de canales de potasio en la tolerancia a la morfina, y viceversa. MÉTODOS: Para el estudio, se usaron ratones albinos suizos de ambos sexos que pesaban entre 25-30 g. El estudio evalúa el efecto de los abridores de canales de potasio (cromacalina, diazóxido y minoxidil) en la tolerancia a la morfina, y viceversa, usando la prueba de la sacudida de la cola y la prueba de la formalina. RESULTADOS: El efecto antinociceptivo de la cromacalina y el minoxidil fue significativamente reducido cuando se le administró a los ratones tolerantes a la morfina, en ambas pruebas conductuales. Sin embargo, se observó un efecto analgésico reducido de diazóxido sobre la tolerancia a la morfina en la prueba de la formalina, pero no en la prueba de la sacudida de la cola. Se observó tolerancia al administrar morfina a animales crónicamente tratados con cualquiera de los abridores de canales de potasio. El mismo efecto fue observado cuando se inyectó la morfina al grupo tratado con una combinación de morfina y cualquiera de los abridores de canales de potasio. CONCLUSIONES: Por consiguiente, este estudio sugiere que tanto la morfina como los abridores de canales de potasio son tolerantes cruzados. Sin embargo, tal interacción ocurre a nivel de los canales de potasio más bien que a nivel de los receptores.

Evaluation of a new fixed duration (12 weeks) multi-drug regimen of bactericidal drugs in multibacillary leprosy.

Leprosy still remains a public health problem mainly in Asia, Africa and South America. The WHO Expert Committee on Leprosy recommended, in 1997, the simplified treatment of leprosy for multibacillary (MB) cases, by reducing the duration of treatment from 24 to 12 months. From the operational point of view even this reduced duration is still long and monthly supervised drug administration may not always be practical in those areas where the accessibility is difficult and health infrastructure weak. The present study was carried out to compare the safety and efficacy of a new fixed duration regimen consisting of four bactericidal drugs with WHO/MDT (MB). METHODS: Thirty adult patients were randomly allocated to two groups. Group 1 (18 patients) received a new regimen of daily rifampicin 600 mg, sparfloxacin 200 mg, clarithromycin 500 mg and minocycline 100 mg for 12 weeks. Group 2 (12 patients) received WHO/MDT (MB) for 12 months. A detailed clinical evaluation and laboratory investigations, BI and MI were done at the baseline, every 4 weeks for 12 weeks, and thereafter every 8 weeks till 48 weeks. Skin biopsies were taken and chest X-rays were done at 0, 12 and 48 weeks. RESULTS: At 48 weeks, the net percentage clinical improvement in group 1 was 73.92% and in group 2 it was 66.66%. The net percentage reduction (NPR) in BI in group 1 was 19.17% and in group 2 it was 18.87% (p = 0.09). NPR in MI in both groups was 100% by 8 weeks, and somewhat faster in group 1. In group 1, 8 patients had mild gastrointestinal side-effect, and 16 had minocycline-induced hyperpigmentation. Three patients in group 1 developed type I reversal reactions. CONCLUSION: The regimen containing daily doses of rifampicin 600 mg, sparfloxacin 200 mg, minocycline 100 mg and clarithromycin 500 mg for 12 weeks was found to be an acceptable, effective and safe alternative regimen for MB leprosy with an additional operational advantage of shorter duration of treatment.

Post-kala-azar dermal leishmaniasis: a histopathological study.

BACKGROUND: Post-kala-azar dermal leishmaniasis follows an attack of visceral leishmaniasis and is caused by the same organism, i.e. Leishmania donovani. METHODS: In the present study, biopsy specimens from hypopigmented macules, nodules or plaques of 25 patients clinically diagnosed as PKDL were evaluated for epidermal and dermal changes and for the presence or absence of Leishmania donovani bodies (LDBs). RESULTS: The hypopigmented macules showed a patchy perivascular and periappendageal infiltrate with no demonstrable LDBs in any of the biopsies. In the nodular and plaque lesions, the infiltrate was diffuse, beneath an atrophic epidermis (74%) and follicular plugging (95.6%) was seen in most biopsies. The infiltrate consisted of lymphocytes, histiocytes and plasma cells in decreasing order of presence. LDBs could be demonstrated in only 10 (43.5%) biopsy specimens from nodular and plaque lesions and were never numerous. CONCLUSIONS: Histopathological features of PKDL are elucidated and discussed.

Dapsone-induced eosinophilic pneumonitis in a leprosy patient.

A leprosy patient with no prior history of respiratory complaints, developed symptoms of dry cough, fever and dyspnea after six weeks of therapy. Peripheral eosinophilia and radiological evidence of pulmonary interstitial infiltrates pointed towards the possibility of drug-induced eosinophilic pneumonitis. The results of relevant tests for other possible pathologies were normal. The resolution of symptoms without any intervention other than withdrawal of the drug and subsequent re-challenge proved dapsone to be the cause.

Mucosal and peri-orificial involvement in post-kala-azar dermal leishmaniasis.

BACKGROUND AND AIMS: Lesions of post-kala-azar dermal leishmaniasis (PKDL) usually affect the skin. Uncommonly, the involvement of oral and genital mucosae has been reported. METHODS: Twenty five patients clinically diagnosed as post-kala-azar dermal leishmaniasis were studied for periorificial and mucosal lesions. Clinical examination, skin smears and biopsy were done for the patients with periorificial or mucosal lesions. RESULTS: Out of 25 patients of PKDL, seven patients had lesions on the oral and/or genital mucosa. Three cases had oral lesions; two had only genital lesions and three patients had both sites involved. All the patients were having skin lesions elsewhere too either as nodules and/or plaque or macules. Conclusion: While examining a case of PKDL, mucosal involvement must also be examined carefully.

Therapeutic trial of sodium antimony gluconate alone and in combination with ketoconazole in post-kala-azar dermal leishmaniasis.

BACKGROUND: Drugs used in PKDL include parenteral sodium antimony gluconate (SAG), amphotericin-B, pentamidine, and ketoconazole (KTZ). SAG is the most effective one. Given alone, SAG has to be given for a long duration, leading to poor patient compliance and treatment failure. This study was carried out to compare the effectiveness of SAG alone and a combination of SAG and KTZ for sixty days. METHODS: Ten patients of PKDL were included in the study. Five patients (Group A) were given SAG intravenously, in the dose of 20 mg/kg per day and five (Group B) were given SAG (intravenously 20 mg/kg per day) and KTZ (200 mg twice daily orally). Both treatment regimens were given for sixty days. RESULTS: In Group A, the nodules and/or plaques showed approximate 80-85% clinical improvement, and macules showed 25-30% improvement. In group B (SAG + KTZ), there was 90-95% clinical improvement in the nodules and/or plaques and 25-30% in macules. CONCLUSION: This study suggests the therapeutic superiority of the combination treatment regimen in a shorter duration but is not conclusive as the number of patients was low. Further trials are recommended.

Cerebral venous thrombosis in ulcerative colitis.

Cerebral venous thrombosis is a rare complication of ulcerative colitis. We report a case of 29 year old male who developed superior sagittal, left lateral and sigmoid sinus thrombosis secondary to ulcerative colitis. He was successfully treated with low molecular weight heparin and steroids.

Anti-inflammatory and analgesic effect of herbal preparation: septilin.

Septilin a proprietary herbal preparation has been reported to have wound healing and immunomodulatory properties. The present study was, therefore, designed to ascertain the anti-inflammatory and analgesic properties of septilin in rats and mice by oral route. Anti-inflammatory activity was assessed by using acute (carrageenan-induced paw oedema), sub-acute (cotton pellet granuloma) and chronic (Freund's adjuvant induced-arthritis) models of inflammation. Administration of septilin in a dose of 500 mg/kg orally produced significant anti-inflammatory effect in all experimental models of inflammation. However, the anti-inflammatory effect was more in chronic model when compared to reference standard drug (Prednisolone). Septilin (500 mg/kg) produced significant analgesic effect on tall flick test. However, the effect was less when compared to morphine (5 mg/kg) but when septilin was combined with subanalgesic dose of morphine (2.5 mg/kg) the analgesic effect was more than the either drug given alone. On GAA induced writhing test septilin produced significant analgesic effect at a dose of 750 mg/kg which was comparable to diclofenac (50 mg/kg). However, subanalgesic dose of septilin (500 mg/kg) when combined with diclofenac (25 mg/kg), analgesic effect was enhanced significantly.

Cryptococcosis in the immunocompromised host with special reference to AIDS.

Cryptococcosis is increasing because of an ever rising population of immunocompromised individuals especially those with acquired immune deficiency syndrome (AIDS). Cryptococcal infection of the central nervous system (CNS) were diagnosed in 149 cases over a period of 19.5 years (January 1978-June 1998). Culture was positive in all cases except three who were already on antifungal therapy. India ink mounts of cerebrospinal fluid (CSF) revealed encapsulated cryptococci in 134, and cryptococcal antigen was detected in 111 of 114 patients tested. A comparison of laboratory and certain clinical parameters in patients with and without associated HIV infection showed that a poor CSF cell response and culture of cryptococci from extra-neural sites was more often associated with HIV infection and was statistically significant. Further, presence of concomitant infection especially tuberculosis, and mortality were higher in the HIV positive group.

Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96).

One hundred patients (95 males, 5 females, mean age at presentation 31.6 +/- 9.4 yr) with various neurological disorders associated with HIV infection during 1989-1996 were evaluated at NIMHANS, Bangalore. Eighty patients belonged to group I associated with opportunistic neuroinfections and 20 to group II--non infectious neurological disorders. Cryptococcal meningitis either alone (n = 31) or associated with tuberculous meningitis (n = 6) was the most common (46.3%) followed by neurotuberculosis either alone (n = 24) or with cerebral toxoplasmosis (n = 4) accounting for 35 per cent. Other opportunistic neuroinfections included cerebral toxoplasmosis, herpes zoster, fulminant pyogenic meningitis and neurosyphilis. Clinical characteristics, diagnostic clues, their laboratory and radiological profiles and problems encountered in diagnosis and management of these opportunistic infections are highlighted. In group II (19 males and one female; mean age of 32.6 +/- 9.4 yr), two patients had cortical dementia, three acute brain stem involvement, two epilepsy and one had features suggestive of progressive multifocal leukoencephalopathy. Two patients of group I during follow up developed cortical dementia. Six had peripheral nervous system involvement similar to Guillain-Barre syndrome. Sixty six patients (63 of group I and 3 of group II) progressed to AIDS, 33 patients from group I and one patient from group II succumbed to the disease. With the rapid increase in the incidence of HIV/AIDS and an increase in the neurological manifestations of HIV/AIDS it is important to recognise the magnitude of the problem for health planning in India.

Intraventricular tuberculous abscess: a case report.

Ventricles can be involved in different ways in neurotuberculosis, however, the occurrence of intraventricular abscess has been rarely reported. We report a young woman who had intraventricular tubercular abscess. Cranial computed tomographic scan showed hypodense ring enhancing lesion in the right lateral ventricle with unilateral hydrocephalus. She underwent parasagittal craniotomy with total excision of the lesion. The pus obtained from the lesion was teeming with acid fast bacilli.

Role of ketamine in convulsions.

It can be concluded from the present study that ketamine showed dose-dependent anticonvulsant effect on MES in mice. It is presumed that this anticonvulsant effect of ketamine could be due to blockade of excitatory amino acid NMDA receptors. It was potentiated by anticonvulsants like diazepam and DPH but was found to be insensitive to naloxone. These findings suggest the involvement of NMDA receptors and their antagonists in epilepsy. Ketamine thus can be given as add-on therapy in refractory cases, and may prove to be useful as an anticonvulsant in future.