Absence Of Specific Therapy Research Articles

Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review

BackgroundKnowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians’ and patients’ expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections.MethodsWe searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points).ResultsWe identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas.ConclusionsOur review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.

MPOX: A RE-EMERGING INFECTION

World Health Organization (WHO)'s declaration on July 23, 2022 regarding Mpox (previously Monkey pox) outbreak appeared as Public Health Emergency of International Concern (PHEIC). Although, WHO, in May 2023 declared an end to the global health emergency for Mpox, but still, it is still prevalent and public awareness should continue.1 This viral Zoonotic contagious disease was first discovered in 1958 when two outbreaks occurred in monkeys kept for research in Denmark, hence the name “monkeypox”. The first human case of monkeypox was recorded in 1970 in the Democratic Republic of Congo.2
 Orthopoxvirus infections can cause a spectrum of febrile rash illnesses in humans, ranging from fairly benign, localized skin infections to severe systemic infections. Other diseases confused with vesicular rashes are smallpox, generalized vaccinia (vaccinia is the virus used in smallpox vaccination), disseminated herpes zoster, disseminated herpes simplex, drug eruptions, erythema multiforme, buffalopox, scabies, enteroviral infections, insect bites, impetigo, molluscum contagiosum, meningococcemia, and idiopathic thrombocytopenic purpura. The most striking feature that distinguishes Mpox from others is the presence of cervical lymphadenopathy, while in all other orthopoxviral infections this feature is absent.3,5
 When suspicion is strong, nucleic acid amplification testing (NAAT), using real-time or conventional PCR Polymerase chain reaction (PCR) is the preferred laboratory test. The recommended specimen type for laboratory confirmation of Mpox is skin lesion material, including swabs of lesion surface and/or exudate, roofs
 from more than one lesion, or lesion crusts. Many individuals infected with Mpox virus have a mild, self-limiting disease course in the absence of specific therapy. However, in the case of severe disease, treatment after infectious diseases consultation should be considered with vaccinia immunoglobulin intravenous (VIGIV), and antivirals brincidofovir or tecovirimat.2 The prognosis for Mpox depends on multiple factors such as previous vaccination status, initial health status, and concurrent illnesses or comorbidities.6 In addition to infection control measures, people need to get vaccinated, where available, for the best protection against mpox.2
 National Institute of Health (NIH), Islamabad, Pakistan, under guidance of Ministry of National Health Services Regulations & Coordination (NHSR&C) has issued the National Guidelines for Mpox. NIH has also developed the bottom-up approach for the flow of information and reporting.7 The relationship between Mpox and smallpox has raised anxieties and misperceptions among the public, patients, and healthcare providers. Misinformation about Mpox has already begun to circulate. The public need to be engaged. Targeted risk-communication strategies should be developed. There is also need for regions to maintain public health preparedness and response. This warrants the strongest medical, scientific, and political global effort.

COVID-19 Vaccination status among Health care workers diagnosed with COVID-19 in a tertiary care institute of Uttarakhand: A Cross-sectional Study

Background: Vaccines are considered as the one of the main pillars in halting and ending the presently on-going coronavirus disease (COVID-19 disease) pandemic which has spread globally since it was first detected in Wuhan, China in December 2019. In the absence of specific therapy, infection prevention practices and mass vaccination remains the mainstay in controlling the disease. Objectives: Objective of the study was to assess COVID-19 vaccination status, socio-demographic and clinical profile among healthcare workers diagnosed with COVID-19. Methodology: A cross-sectional survey from 1st March 2021 to 30th June 2021 among healthcare workers who were diagnosed with COVID-19 in a tertiary care institute of Uttarakhand, India was conducted, and universal sampling was used. Institutional Ethics Committee approved this study. Results: Total 662 healthcare workers were diagnosed with COVID-19. 429 (64.8%) of these COVID-19 diagnosed healthcare workers had received either single (129,30%) or both dose (300,70%) of COVID-19 vaccine while remaining 233 (35.2%) belonged to non-vaccinated group. History of exposure to COVID-19 positive patients was higher in vaccinated (66.4%) than in non-vaccinated group (55%) (p = 0.004). Hospitalisation was found to be higher among non-vaccinated (5.6%) than vaccinated group (2.3%) (p = 0.029). Conclusions: This study concludes that being vaccinated against COVID-19 disease provides protection against severe infection and reduces the need for hospitalization.

Infezione congenita da citomegalovirus e ipoacusia

Background - Cytomegalovirus (CMV) infection is the most common of congenital infections, with a prevalence of 0.3-1.2% in industrialized countries and is the most frequent non-genetic cause of permanent hearing loss in children, with an incidence ranging from 0.2 to 2%. Since there is no antenatal therapy or vaccine against CMV and since many patients with congenital CMV (cCMV) do not experience sequelae even in the absence of specific therapy, a universal screening programme has not been established. Current protocols provide test for the detection of cCMV in case of failure at newborn hearing screening. Aim - This article aims to analyze the pros and cons of the different screening approaches for cCMV, through an overview of the topic based on the most recent literature. Materials and Methods - The recent national and international literature on cCMV screening has been examined through a narrative review. Results - As part of the screening and early identification programmes for neonatal hearing loss, current procedures include a search for cCMV on urine or saliva within 3 weeks of life, following a positive result (Refer) at newborn audiological screening. This approach enables to recognize cCMV infection in newborns suffering from isolated hearing loss, which is already present at birth, however it does not allow cases of CMV-related hearing loss occurring in the postnatal period or late in childhood to be recognized. A universal newborn cCMV screening, in conjunction with audiological screening, would have the advantage of identifying all infants infected with cCMV, including 10%-15% of asymptomatic conditions at birth who may develop late hearing loss. One of the major obstacles to the establishment of universal cCMV screening is the unknown cost of its application and a clear understanding of the sensitivity and specificity of the cCMV test. Conclusions - Strategies are needed to identify children with congenital CMV infection at risk for developing late-onset hearing loss. A universal newborn screening to ensure timely recognition of children with cCMV, close audiological surveillance and possible early treatment at the onset of the first hearing symptoms should be provided.

Pathophysiological Prerequisites and Therapeutic Potential of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis

Due to the high morbidity and mortality, the problem of severe alcoholic hepatitis has not lost its relevance to date. In the absence of specific therapy, the associated to him one-month survival rate is low, and mortality rates reach 30-50 %. Although the use of corticosteroids is a scientifically proven first-line treatment for severe alcoholic hepatitis, a short-term response is observed in approximately 60 % of patients with no long-term survival benefits compared to placebo. It should also take into account the occurrence of adverse side reactions to their use in about 50 % of patients, as well as the risk of complications, in particular, bacterial and fungal infections. The second-line drugs, for example, pentoxifylline, etanercept, infliximab, N-acetylcysteine, etc. in severe alcoholic hepatitis did not show an improvement in the clinical outcome. The modern guidelines discuss the feasibility of liver transplantation in carefully selected patients who do not respond to corticosteroid treatment with severe alcoholic hepatitis. Nevertheless, due to numerous contradictions, it is too early to talk about the introduction of this approach into clinical practice. In recent years, some progress has been made in understanding the pathophysiological mechanisms of the development of alcoholic hepatitis, which served as an impetus for new directions of its pathogenetic therapy. One of them is the techniques that provide intestinal eubiosis, in particular, through the fecal microbiota transplantation. The purpose of the review was to describe the pathophysiological prerequisites and therapeutic potential of fecal microbiota transplantation from healthy donors to patients with severe alcoholic hepatitis. Experimental studies have shown a positive effect of fecal microbiota transplantation on the intestinal microflora, which led to a weakening of alcohol-induced liver damage. In patients with severe alcoholic hepatitis, it improved the severity of its symptoms and contributed to increased survival compared to those receiving corticosteroids. These preliminary results are encouraging and create conditions for further clinical trials involving a large cohort of patients with severe alcoholic hepatitis, which will allow us to identify those for whom fecal microbiota transplantation will be most effective with minimal risk of complications.

Defining improvement in chronic kidney disease: regression and remission.

International definitions exist for chronic kidney disease (CKD) progression and kidney failure but despite evidence that kidney function may improve, there are no agreed definitions for regression and remission of CKD. In the light of recent novel kidney protective therapies and the promise of regenerative medicine to reverse kidney damage, it is time to critically examine these neglected aspects of CKD epidemiology. We propose that CKD regression is viewed as a process of improvement defined as a sustained increase in glomerular filtration rate (GFR) by ≥25% and an improvement in GFR category or increase in GFR of 1≥ml/min/year, whereas remission is considered a category of improvement defined as GFR ≥60 ml/min/1.73m 2 and urine albumin to creatinine ratio <30 mg/g. Several recent studies have reported improvement in kidney function in populations with CKD, even in the absence of specific therapy. Regression and remission of CKD are associated with increased likelihood of sustained improvement in kidney function as well as improved survival. Further research is warranted to validate the proposed definitions and investigate associated mechanisms. We look to a future in which the goal of therapy is not merely to slow CKD progression but to improve kidney function and seek a cure.

Clinical characteristics of patients hospitalized to the Ukrainian expert-consultative center of pulmonary hypertension for adults

Pulmonary arterial hypertension (PAH) is a group of rare, malignant diseases that, without optimal treatment, quickly lead to death (the average survival of patients in the absence of specific therapy is 2.8 years from diagnosis). This nosology is most often diagnosed at an earlier age and mainly in female patients. The global trend indicates a predominance of PAH in women over men in 2–4 times greater.
 The objective of the paper to study the condition of inpatients to determine the strategy of medical care and identify ways to improve the pharmaceutical supply of patients with pulmonary arterial hypertension.
 The object of the study were the results of a retrospective analysis of medical records of inpatients 93 patients hospitalized at the Ukrainian Expert-Consultative Center for Pulmonary Hypertension for Adults, established on the basis of NSC «Strazhesko Institute of Cardiology of the National Academy of Medical Sciences of Ukraine». Analytical, documentary, informational, graphic and retrospective research methods were used during the research.
 According to the results of a retrospective analysis of 93 medical records of inpatients who were registered and treated at the Ukrainian Expert Advisory Center for Adults for the period from 2018 to 2021, it was found that almost all patients with PAH have heart problems and other concomitant pathological conditions.
 The period of inpatient treatment consisted of maintenance therapy with diuretics (spironolactone, furosemide, triphas, torside, torasemide), anticoagulants (warfarin), cardiac glycosides (digoxin) and iron supplements (maltoferfol) and specific therapies using calcium channel blockers (amlodipine), prostacyclin analogues (ventavis), endothelin receptor antagonists (bosentan) and phosphodiesterase type 5 inhibitors (sildenafil, no-lag).
 Patients with PAH were hospitalized for 2 days to 31 days, the average number of bed-days was 8.75 days per 1 patient.
 Thus, the results of the study of the clinical characteristics of patients hospitalized at the Ukrainian Expert Advisory Center of Pulmonary Hypertension for Adults, indicate the need to determine the technology of specific therapy of PAH with pharmacoeconomic analysis.

Relationship between the coronavirus epidemic and the use of complementary and alternative medicine prior to elective surgical procedures

The coronavirus epidemic caused by SARS-CoV-2 from Wuhan at the end of 2019 had considerable impact on our lives. In the absence of specific therapy, some people have resorted to alternative therapies. The aim of our study was to explore the effect of the coronavirus epidemic on the patients' attitudes toward complementary and alternative medicine. We have performed anonymous questionnaire survey among patients of a Hungarian university hospital and a city hospital waiting for elective surgery between August 3, 2020 and December 18, 2020. We received 279 questionnaires, the response rate was 69.7%. As a result of the coronavirus epidemic, 91.4% of the respondents did not change their opinion about complementary and alternative treatments, 8.2% were more optimistic about them. 16.8% of respondents were optimistic, 25.4% rejected, and 57.7% did not form an opinion about the disease-preventing effect of complementary therapy. A quarter of respondents (24.7%) had used complementary therapies in their lifetime, with only 10% of respondents using such therapies to prevent coronavirus infection. As a result of the pandemic, no one started using complementary therapies. 55.6% of the respondents used a herbal preparation during their lifetime. In the course of the epidemic, a high proportion of respondents (27.5%) used herbal preparations; no correlation was found between the use of the treatment and the socio-demographic factors examined. The use of herbs was lower among cancer and thromboembolic patients. Based on our study, the use of complementary therapies presumably decreased due to the restrictions imposed in the epidemic, however, the use of herbs did not change significantly. One-tenth of the respondents used naturopathic cure to prevent coronavirus infection. Orv Hetil. 2021; 162(42): 1678-1686.

Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum.

Active microcalcification of elastic fibers is a hallmark of pseudoxanthoma elasticum and it can be measured with the assessment of deposition of 18F-NaF using a PET/CT scan at the skin and vascular levels. It is not known whether this deposition changes over time in absence of specific therapy. We repeated in two years a PET/CT scan using 18F-NaF as a radiopharmaceutical in patients with the disease and compared the deposition at skin and vessel. Furthermore, calcium score values at the vessel wall were also assessed. Main results indicate in the vessel walls that calcification progressed in each patient; by contrast, the active microcalcification, measured and target-to-background ratio showed reduced active deposition. By contrast, at skin levels (neck and axillae) the uptake of the pharmaceutical remains unchanged. In conclusion, because calcification in the arterial wall is not specific for pseudoxanthoma elasticum condition, the measurement of the deposition of 18F-NaF in the neck might be potentially used as a surrogate marker in future trials for the disease.

Effectiveness of Convalescent Plasma Therapy in Critically Ill COVID-19 Patients: Early Experience from a Dedicated ICU of Bangladesh

Introduction: The management of severe or critical COVID-19 patients in the ICU includes supportivecare as well as repurposed drugs and revival of old strategies like human convalescent plasma therapy(CPT) in the absence of specific therapy against SARS-CoV-2 virus. CPT appears to be an attractivetreatment option as passive antibody transfer, but efficacy remains controversial. Objectives: To determine the effectiveness of convalescent plasma therapy in management of criticallyillCOVID-19 patients admitted at the dedicated intensive care unit of Kurmitola General Hospital, Dhaka. Study Method: All patients admitted in the ICU of Kurmitola General Hospital, Dhaka from 1st May to30th September 2020 were included in this retrospective observational cohort study. The protocolwasapproved by the Ethical and Scientific Committee of the hospital. The clinical and treatment data ofall participants were collected; and the association of CPT and mortality benefit was observed betweenthe patients who received plasma therapy during ICU stay and who didn’t. The statistical analysis wasperformed using the Windows based statistical software package SPSS version 25. Results: A total of 228 critically illCOVID-19 patients were admitted to the ICU of Kurmitola GeneralHospital in the specified time period. Among them, 160 (70%) were male and 68 (30%) females. Mean agewas 57.97 (95% CI 56.23-59.70) years. Important co-morbidities were obstructive airway diseases 160(70.17%), hypertension 117 (51.31%) and diabetes mellitus 103 (45.17%). Only 53 (23.25%) patients receivedCPT during ICU stay. The median day of receiving CPT from the day of symptom onset was 12 (IQR 10-14) days in the survivor group and 18 (IQR 16-19) days in the non-survivor group (p<0.0001). All-causeICU mortality was 29 (54.7%) in CPT group vs. 115 (65.7%) in Non-CPT group (p=0.146). The odds ratioof survival in CPT group was 0.757 (95% CI 0.528-1.085). Conclusion: This retrospective cross-sectional study suggested that the efficacy of use of convalescentplasma in critical or severe COVID-19 patients admitted to ICU is conflicting for mortality benefit. JBSA 2021; 34(1): 26-31

Adaptive immunity against SARS-CoV-2

The impact of host adaptive immune response on COVID-19 has now become a critical issue in absence of specific therapy and immunotherapies. In SARS CoV-2 infection, the immune response is thought to contribute both to the pathogenesis of the disease and to protection during its resolution. While mild cases develop an immune response that contributes to host protection, immunity of severely infected patients is a balance between harmful and protective immune responses. The severity of the disease has raised many questions about the kinetic, amplitude and the quality of adaptive immunity to the virus and its generation during the early phases of infection in severe, mild and asymptomatic patients. The role of antibody and CD4+ and CD8+ T cell responses have been studied and the development of an adaptive immunity seems to correlate with convalescence. The bioinformatics study of the T and B epitopes of coronaviruses has raised the question of the existence of cross-immunity between SARS-CoV-2 and other coronaviruses such as MERS-CoV and SARS-CoV. In this review, we discuss the adaptive immune responses and their potential roles in protection during COVID-19.

Current status and future perspective of coronavirus disease 2019: A review

A novel infectious disease named coronavirus disease-2019 (COVID-19) first emerged in Wuhan, China, in December 2019 and rapidly spread worldwide. In March 2020 the World Health Organization declared a global pandemic which is the worst global public health crisis in over 100 years. On 14 June 2020, almost eight million confirmed cases of COVID-19 and more than 430,000 deaths globally were reported. Over 200 countries have been affected so far. COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the absence of specific therapy and vaccine, effective infection control intervention, particularly self-hygiene and social distancing, is the only way to prevent the spread of SARS-CoV-2. The lessons learned from this pandemic will be useful for successful management of the second wave of COVID-19 which is expected in autumn or winter.

A Systematic Approach to the Cutaneous Lymphoid Infiltrates: A Clinical, Morphologic, and Immunophenotypic Evaluation.

The evaluation of cutaneous lymphoid infiltrates, both neoplastic and inflammatory, occurs very frequently in routine dermatopathologic examination and consultation practices. The "tough" cutaneous lymphoid infiltrate is feared by many pathologists; skin biopsies are relatively small, whereas diagnostic possibilities are relatively broad. It is true that cutaneous lymphomas can be difficult to diagnose and that in many circumstances multiple biopsies are required to establish a correct diagnostic interpretation. As a reminder, one should understand that low-grade cutaneous lymphomas are indolent disorders that usually linger for decades and that therapy does not result in disease cure. It is also important to remember that in most circumstances, those patients will die from another process that is completely unrelated to a diagnosis of skin lymphoma (even in the absence of specific therapy). To use a clinicopathologic, immunophenotypic, and molecular approach in the evaluation of common lymphocytic infiltrates. An in-depth analysis of updated literature in the field of cutaneous lymphomas was done, with particular emphasis on updated terminology from the most recent World Health Organization classification of skin and hematologic tumors. A diagnosis of cutaneous lymphoid infiltrates can be adequately approached using a systematic scheme following the proposed ABCDE system. Overall, cutaneous T- and B-cell lymphomas are rare and "reactive" infiltrates are more common. Evaluation of lymphoid proliferations should start with a good sense of knowledge of the clinical presentation of the lesions, the clinical differential considerations, and a conscientious and appropriate use of immunohistochemistry and molecular tools.

Oxygen-ozone therapy in meningoencephalitis and chronic fatigue syndrome. Treatment in the field of competitive sports: case report

Our study was born from the observation of a clinical case of a boy who arrived in the Emergency Room of our hospital for persistent hyperpyrexia, headache and prolonged emetic episodes and complaining of objective photophobia and dizziness. The patient underwent haematochemical tests, chemical-physical examination of Chronic Fatigue Syndrome (CFS), negative for bacteria, negative for Neisseria Meningitidis, Escherichia Coli 121, Haemophilus Influenzae, Stafilococcus Pneumoniae, Stafilococcus Agalactiae and with slightly positive reaction to Pandy’s test; he was subjected to neurological examination, to Nuclear Magnetic Resonance of the brain and encephalic trunk with contrast agent which resulted negative, and to EEG that showed a slightly slowed-down brain electrical activity, in right occipital region, and frontal irritative abnormalities. Given these clinical and instrumental investigations, an acute meningoencephalitis was diagnosed. During his hospitalization, the patient was treated with intravenous antibiotic therapy and intravenous antiviral therapy for 12 days. At discharge, in the absence of specific therapy, and considering the protraction of the cephalic, dizzying, asthenic and myalgic symptoms and in relation to hematochemical and serological tests (positive for antibodies to Herpes 1 IgG), Epstein Barr Virus antibodies (positive for Viral Capsid Antigen IgG and IgGE BNA, for Extractable Nuclear Antigen and IgG Cytomegalovirus) he was diagnosed a Post-infectious CFS. The patient was treated with Oxygen Ozone Rectal Insufflative Therapy on a bi-weekly basis for 4 weeks, associated with Micetrin, a dietary supplement with sweetener based on Vitamin C, Shitake, Reishi, Maitake, Cordyceps, Magnesium and SOD, continued the treatment on a weekly basis for a further 4 weeks until the complete remission of the symptoms of asthenic, neurological and clinical parameters.

Trends of Dengue Disease Epidemiology.

Dengue disease is an emerging mosquito-borne viral infection transmitted between humans by Aedes spp. that are distributed mainly in the tropical and subtropical region along with chikungunya and zika diseases. The distribution of dengue disease is influenced by local variation, such as geography, rainfall, temperature, and rapid urbanization or migration. The epidemy of mosquito-borne infection significantly led to increased number of cases and hyperendemicity which induce a more severe form of dengue accompanied by cocirculation of chikungunya and zika. The rapid global spreading of dengue disease created public health burdens that are presently unfulfilled by the absence of specific therapy, simple diagnosis tool for the early phase, and effective and efficient vector control system. This review highlights the current situation of dengue distribution, epidemiology, and new strategies for early dengue diagnosis and risk prediction of severity that can be used to improve oversight and alleviate the heavy burden of the disease.

Diagnostic et traitement des déficits du cycle de l’urée à l’âge adulte

Urea cycle disorders (UCDs) are inborn errors of metabolism in which the clinical picture is mostly due to ammonia intoxication. UCD onset may be observed at any age. Acute decompensations of UCDs include neuro-psychiatric symptoms such as headache, confusion, convulsions, ataxia, agitation or delirium, as well as digestive symptoms, namely nausea and vomiting along with abdominal pain. Acute decompensations may lead to an irreversible coma in the absence of specific therapy. The first step is to measure promptly ammonemia in such patients, and start appropriate therapy on an emergency basis.

Effect of adapted physical exercise on satellite cells from skeletal muscles of old mice: ex vivo and in vitro analyses

Aging is characterized by loss of skeletal muscle mass termed sarcopenia, which contributes to frailty, disability and premature death (1). The mechanisms leading to sarcopenia are manifold, the decline in muscle regeneration efficiency playing a crucial role. In the absence of specific therapies, studies have stressed the importance of physical exercise as an effective approach to prevent/limit the sarcopenic drive (2,3). We investigated the effect of adapted exercise on the number and myogenic properties of satellite cells (SCs) in the quadriceps femoris and gastrocnemius muscles of old mice (28 months). Both muscles contain about 90% of type II fibers, which are especially affected by sarcopenia (4). We compared old exercised mice with old sedentary mice, adult sedentary mice (12 months) being the control. SCs were identified and quantified ex vivo; the proliferation and differentiation potential of SC-derived myoblasts from the three groups of mice was studied in vitro. Ultrastructural morphology and immunocytochemistry at light and electron microscopy level localized molecular markers of SC activation and protein factors involved in RNA transcription and splicing. Results showed that: 1) physical exercise induces an increase in the total number as well as activated fraction of SCs compared with sedentary old specimens; 2) myoblasts from exercised old muscles show morphological features and nuclear activity quite similar to myoblasts from adult subjects, whereas myoblasts from non-exercised old muscles exhibit structural and functional alterations suggestive of a reduced metabolic activity; 3) myotubes differentiated from myoblasts of exercised old muscles resemble those from adult myoblasts, whereas myotubes from non-exercised old muscles show marked structural alterations. Physical exercise induces numerical increase and activation of SCs in old muscles and improves their capability to differentiate into structurally and functionally complete myotubes. Adapted physical exercise may represent a non-pharmacological approach to stimulate SCs, enhancing muscle quality at very advanced age. MC is a PhD student of the Doctoral Program “Multimodal Imaging in Biomedicine” (University of Verona).

Clinical improvement of vasovagal syncope in the absence of specific therapies: The Seinfeld effect.

Vasovagal syncope can persist for decades and recur sporadically but many patients appear to improve after being seen in specialty clinics. The absence of specific and proven effective therapy raises the possibility that this might be due to regression to the mean or to a placebo effect. However, analysis using the Poisson distribution indicates the extreme unlikeliness that regression to the mean is the explanation. A main cause of the placebo effect is expectancy. Subject expectancy is the influence of the subject's anticipation of benefit on outcomes, and observer expectancy is the influence of investigator or physician attitudes and behavior on subject response. Ample data support the role of expectancy in outcomes of syncope patients. Moreover, expectancy can vary depending on the type of ineffective intervention. Interestingly, studies in which patients are blinded but the investigator is not show similar patient benefits compared with completely open label studies consistent with a strong observer expectancy effect due to physician-subject interaction. These results suggest the paramount importance of properly conducted randomized clinical trials in assessing biomedical interventions, and also illuminate the powerful potential of studies aimed at enhancing the expectancy effect on patient outcome.

Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations.

In the absence of specific therapy, the 15%–20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin), the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab’s clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab’s incorporation into clinical practice.

Ebola virus outbreak and its management: An overview

Ebola virus disease (EVD) is a severe, often fatal disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). The current outbreak is in West Africa involving countries of Guinea, Liberia, Sierra Leone and Nigeria (as on August 6, 2014). The infection is transmitted to humans through close contact with the blood, secretions, organs or other body fluids of infected nonhuman primates. Clinically, patient should be diagnosed based on signs and symptoms with history of travel from Ebola affected areas or exposure to EVD patients. All suspected patient should be investigated for IgM (enzyme-linked immunosorbent assay), antigen detection, and reverse transcriptase-polymerase chain reaction to confirm. Currently, no specific therapy is available that has demonstrated efficacy in the treatment of EVD. In the absence of specific therapy, a number of modalities have been tried. General medical support is critical. Steriod therapy has no role. There is no role for antibiotics unless there is evidence of secondary bacterial infection. Nutrition is complicated by the patient's nausea, vomiting, and diarrhea. Good hydration is to be ensured with good amount of protein supplement. Experimental vaccines are under trial.