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.

Unexpected Mycoplasma hominis infection in two renal transplant recipients traced back to the same donor by whole-genome sequencing.

Mycoplasma hominis is a common colonizer of the lower genitourinary tract. Although its clinical relevance for causing urogenital infections in immunocompetent individuals is controversial, this bacterium has been involved in severe invasive infections in allograft recipients. In this report, we describe two cases of M. hominis infection in two young renal transplant recipients within the first month post-transplant. Although at first no epidemiological link between the two cases had been suspected, whole-genome sequencing (WGS) analysis showed that both isolates were identical, highly suggestive of an origin with the common organ donor.

Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland.

Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15-77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.

Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study.

BACKGROUND: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study. METHODS: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT. RESULTS: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr. CONCLUSIONS: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr.

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Long-term remission of clear cell carcinoma of the cervix after chemoradiation with 109 cycles of paclitaxel: a case report and literature review.

BACKGROUND: Clear cell carcinoma of cervix (CCCC) is a rare cervical neoplasm that is usually associated with diethylstilbestrol (DES) exposure in utero as a primary risk factor. Advanced stage disease typically has poor outcomes and no evidence-based approach exists to guide clinicians in treating this rare disease. CASE: The authors report a case of locally advanced CCCC in a 37-year-old Caucasian female. She underwent chemoradiation therapy that included 109 courses of paclitaxel chemotherapy until no disease could be detected on imaging studies. She is now disease-free 13 years after discontinuing chemotherapy. CONCLUSION: A prolonged course of single agent paclitaxel after completing standard radiation therapy was successful in achieving remission in a patient with this rare disease.

Clinical outcomes and the role of adjuvant therapy sequencing in Type II uterine cancer following definitive surgical treatment.

PURPOSE OF INVESTIGATION: Because of rarity, consensus on adjuvant therapies for Type II endometrial cancers (BC) remains undefined. Reporting their institutional outcomes, the present authors assessed the impact of adjuvant therapies on recurrence and overall survival in women with 2009 FIGO Stage I-III Type II BC. MATERIAL AND METHODS: The authors identified 108 women, treated with definitive surgery between 2000-2013, with pathologically-confirmed Type II EC (non-endometrioid [NEM, n=801 and high grade endometrioid [G3EEC, n=28]) Cox proportional hazard models were used to assess the effect of prognostic variables on disease-free (DFS) and overall survival (OS). Kaplan-Meier method was used to assess survival. RESULTS: Of the 108 women, 83 (77%) were African American (AA). Fifty-nine (55%), 12 (11%), and 37 (34%) were Stage I, II, and III, respectively. Ninety-seven patients received adjuvant therapy: 52 (radiation only), four (chemotherapy only), and 40 (combined). During follow-up (median 41 months), 44 patients (41%) recurred. Five-year DFS was 53% overall (48% [NEM], 80% [G3EEC]). Five-year OS was 75% overall (68% [NEM], 95% [G3EEC]). On multivariate analysis, lower stage and adjuvant radiation improved DFS. Higher stage, NEM, and increasing age were poor prognostic indicators of OS. CONCLUSION: Representing a large single institutional cohort for Type II BC, the present study's observed sur- vival rates are consistent with previous studies, despite the relatively high frequency of carcinosarcoma and Stage III/nodal disease. The protective effect on recurrence was not lost when radiation was delayed for chemotherapy. The present results support a multimodal adjuvant approach for treating all stages of invasive NEM EC.

Effectiveness of weekly azathioprine pulse in the treatment of chronic plaque psoriasis: an open-label study.

BACKGROUND: Azathioprine is a potent immunosuppressive drug that has been used in many immune-mediated diseases. There are a few reports of its use in psoriasis; however, azathioprine weekly pulse doses have not been evaluated in this disease. AIM: The objective of this study was to evaluate the therapeutic effectiveness of weekly oral pulse doses of azathioprine for the treatment of chronic plaque psoriasis, and to determine the side effects of this regimen both clinically and biochemically. METHODS: In this open-label clinical trial, a 300 mg bolus dose of azathioprine was given once every week orally for 24 weeks to patients with chronic plaque psoriasis having body surface area involvement of ≥ 10% and Psoriasis Area and Severity Index (PASI) of ≥ 10. Patients were evaluated every 4 weeks for 24 weeks to determine the response to treatment and any adverse effects (AEs), and then followed up for a further period of 12 weeks to determine any relapse of the disease. RESULTS: There were 50 patients in the study, of whom 28 (56%) completed the 24 weeks of treatment and 27 (54%) completed the 12-week post-treatment follow-up. Azathioprine 300 mg weekly pulse was effective in achieving PASI 75 in 42% of patients, PASI 90 in 36% of patients and PASI 100 in 22% of patients. In five patients (10%), the therapy had to be withdrawn due to AEs. CONCLUSION: Weekly azathioprine pulse appears to be an effective treatment for chronic plaque psoriasis, and can be used as an alternative therapy to other available therapeutic agents.

Syk mediates airway contractility independent of leukocyte function.

BACKGROUND: Syk, an immune regulatory tyrosine kinase, plays a role in inflammatory disease processes. We recently reported a role for epithelial expression of Syk in the airways hyper-responsiveness in response to air pollution in a mouse model of asthma. The aim of this study was to further investigate the role of Syk in airway contractility in response to methacholine (MCh) and particulate matter (PM) air pollutants, in the absence of underlying inflammation. METHODS: We used Syk(flox/flox) //rosa26CreER(T) (2) conditional Syk knockout mice to evaluate respiratory mechanics and MCh responsiveness following PM exposure in vivo using the ventilator-based flexiVent system. RESULTS: While total and differential cell counts in bronchoalveolar lavage fluid were similar between the Syk(flox/flox) and Syk(del/del) mice, central airways respiratory resistance (RN ) to MCh was significantly augmented following PM exposure between Syk-intact (Syk(flox/flox) ) and Syk-deficient (Syk(del/del) ) mice (RN (max) : 2.06 ± 0.29 vs. 1.29 ± 0.10, respectively; p < 0.05, n = 8-10/group). We employed live videomicroscopy to investigate changes in airway luminal diameter using ex vivo lung slices, which were devoid of circulating leukocytes. MCh reduced the airway luminal area of Syk(flox/flox) mice to 81.1 ± 1.4% of baseline, which was virtually abrogated in Syk(del/del) mice (luminal area = 93.2 ± 0.5%, n = 5/group, p < 0.05). In response to PM exposure, Syk(flox/flox) airways contracted to 73.8 ± 2.7% of baseline luminal diameter, whereas Syk(del/del) airways exhibited minimal contractility to PM and MCh (90.0 ± 1.3% of baseline, n = 5/group, p < 0.05). CONCLUSIONS: These observations suggest that Syk mediates airway contractility in the normal and allergic airways, independent of its role and function in leukocytes, and supports a paracrine role for airway epithelial Syk in modulating airway smooth muscle activity.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

The tangled web: a study of knowledge and attitude towards leprosy from a tertiary care hospital in India.

Leprosy stands tall among the oldest and most misunderstood diseases of man. Today leprosy is easily treated; unfortunately, persistent misconceptions result in unnecessary stigmatization. Thus the present study aims to assess the knowledge and attitudes regarding leprosy in people with and without leprosy, factors affecting the same; and to study their relationship with treatment status in leprosy patients. Detailed knowledge and attitude questionnaires were administered to 260 subjects (100 leprosy patients, 60 family members of leprosy patients and 100 people with non-leprosy skin diseases) at AIIMS, New Delhi. Crude scores based on subject responses were used for inter-group comparisons. Leprosy patients had significantly higher knowledge scores than family members who in turn scored significantly higher than people with other skin diseases. Leprosy patients had fair knowledge about common symptoms, but awareness about MDT was low. Delayed diagnosis and non-compliance were common. Attitudes did not differ between groups. Fear of the leprosy-affected and reluctance for physical contact, food sharing and marriage were prominent. Treated leprosy patients had the highest knowledge scores. Higher education and greater knowledge scores were positive predictors of attitude. Knowledge and attitude scores showed significant positive correlation. Knowledge and attitude towards leprosy are unsatisfactory. Improving knowledge may help to improve attitudes. In the post-elimination era, we must incorporate education about the disease into routine care of leprosy patients and focus on community education about leprosy.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

[Fever and lymphadenopathy. Report of 4 cases of tularemia]. / Fieber und Lymphadenopathie. Bericht über 4 Tularämiefälle.

We report on 4 patients with different types of tularemia acquired in Switzerland or nearby countries. All patients presented with fever, moderate to highly elevated signs of inflammation, and local lymphadenopathy. Additionally, 3 patients did not respond to empirical antimicrobial therapy with aminopenicillins. A tick bite was identified as mode of transmission in 2 patients, while 1 patient showed a possible connection to a tick bite. The route of transmission for the fourth patient remained unknown. The diagnosis of tularemia was either based on positive serology, on a positive polymerase chain reaction (PCR) from the lymph node samples or on positive blood cultures. The treatment in adult patients was ciprofloxacin 500-750 mg twice daily orally for 3 weeks. The pediatric patient was treated with gentamicin 4 mg/kg i.v. once daily for 1 week and ciprofloxacin 15 mg/kg twice daily orally for another 2 weeks. All patients recovered completely. Due to the increasing incidence of tularemia in Switzerland, this infection should be considered in patients with fever and lymph node enlargement particularly after tick bite. We recommend treatment with ciprofloxacin orally for 14-12 days.

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

Legionella pneumophila serogroup 3 infection: importance of serology.

We present a case of Legionella pneumophila serogroup 3 (LP3) infection in a patient with severe community-acquired pneumonia (CAP). The diagnosis was complicated by an initial equivocal L. pneumophila urinary antigen test, followed by two negative samples. LP3 was cultured from a sputum sample and the diagnosis was confirmed by serology 15 days into the admission. This case highlights the importance of considering non-LP1 serogroups as causes of CAP and the role of serological testing in diagnosis.

[Fever, coughing and dyspnea in a 38-year-old female kidney transplant recipient]. / Fieber, Husten und Dyspnoe bei einer nierentransplantierten 38-jährigen Patientin.

This article reports on a 38-year-old kidney transplant patient who presented with fever, coughing and dypnea. The patient was immunosuppressed with mycophenolate and prednisone. Due to the suspicion of community acquired pneumonia antibiotic treatment was initiated and the patient was admitted to the intensive care unit. Despite antibiotic treatment the condition did not improve and in the subsequently performed bronchioalveolar lavage parainfluenza virus was diagnosed.Infections with respiratory viruses can be fatal in immunosuppressed patients. Human parainfluenza virus is the third most common pathogen of viral pneumonia. Molecular genetic detection methods allow fast and sensitive diagnosis of respiratory materials. As the treatment options are limited for these infections prophylactic measurements are important.

Evidence for intensive LDL-C lowering for acute coronary syndrome: Recommendations from the Lipid Association of India.

Patients with acute coronary syndrome (ACS) have a high risk of subsequent adverse cardiovascular outcomes, particularly within the first 30 days. Although it is well documented that initiation of statin therapy in the setting of ACS improves short- and long-term cardiovascular outcomes, and achievement of lower levels of low density lipoprotein cholesterol (LDL-C) incrementally improves outcomes, many patients with ACS have persistent hypercholesterolemia after discharge from the hospital. This is a missed opportunity that prompted the Lipid Association of India to develop recommendations for earlier initiation of more aggressive LDL-C lowering treatment, particularly for patients of South Asian descent who are well-documented to have earlier onset of more aggressive atherosclerotic cardiovascular disease. The Lipid Association of India recommends individualized aggressive LDL-C goals after ACS, which can be rapidly achieved with high intensity statin therapy and subsequent goal-directed adjunctive treatment with ezetimibe and PCSK9 inhibitors. Improved treatment of hypercholesterolemia achieved within weeks after ACS has the potential to reduce the high rate of morbidity and mortality in these high risk patients.