Dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor has been consistently shown to reduce recurrent major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) compared with aspirin monotherapy but at the expense of an increased risk of significant bleeding. Among patients with stable CAD undergoing PCI with drug-eluting stents (DES), shorter duration of DAPT (3–6 months) were shown non-inferior to 12 or 24 months duration concerning MACE but reduced the rates of major bleeding? Contrariwise, prolonged DAPT durations (18–48 months) reduced the incidence of myocardial infarction and stent thrombosis, but at the cost of an increased risk of majör bleeding and all-cause mortality. Until more evidence becomes available, the choice of optimal DAPT regimen and duration for patients with CAD requires a tailored approach based on the patient clinical presentation, baseline risk profile and management strategy. Patients with acute coronary syndromes (ACS) and a history of atrial fibrillation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. This article provides a contemporary state-of-the-art review of the current evidence on DAPT for secondary prevention of patients with CAD and its future perspectives.
Hydrogel-based formulations hold significant promise for treating ocular diseases that impact the posterior segment of the eye. These formulations exhibit the ability to surmount ocular barriers and offer sustained drug release, rendering them efficacious drug delivery systems. This article addresses the challenges linked to treating disorders affecting the posterior eye segment and underscores the imperative for less invasive drug delivery methodologies. We further delve into diverse contemporary ocular dosage forms, encompassing gels, nanostructures, and implants, with a specific emphasis on hydrogels. Hydrogels offer several merits, including precise targeting, sustained release, enhanced bioavailability, and non-invasiveness. Moreover, they curtail the risk of adverse effects and foster patient adherence. An enthralling advancement is the amalgamation of hybrid drug delivery systems, integrating nanoparticles, liposomes, dendrimers, and stimuli-activated nano-systems, with hydrogels for posterior eye ailment treatment. These hybrid nano-systems exhibit promise in enhancing drug stability, prolonging drug release, and pinpointing specific tissues within the posterior segment. We also provide an overview of ongoing clinical trials and approved hydrogel-based drug delivery systems, like Retisert and Ozurdex. These systems have demonstrated efficacy in managing chronic non-infectious uveitis, Age-related Macular Degeneration (AMD), and diabetic macular edema. Nevertheless, challenges persist, including optimizing bioavailability, maintaining drug stability, and implementing personalized treatment approaches. The incessant evolution of gel-based drug delivery systems stands to substantially enhance patients’ quality of life and establish new benchmarks in treating posterior eye diseases. The future of ophthalmology brims with excitement, as gel-based drug delivery systems hold the potential to revolutionize ocular therapies, providing effective remedies for an array of vision-related afflictions.
Development of genetic profiles from the biological mixtures has remained challenging, although modern-day technologies may help forensic scientists to attain a reliable genetic profile in the identification of the accused.
In the case of rape, vaginal swab exhibits usually contain epithelial cells of victims and sperm cells of accused, such samples are more challenging when there is more than one contributor. In such cases, separation of distinct cells from a mixture that includes blood cells, epithelial cells and sperm cells for their single genetic profile is important.
In the last ten decades several new techniques were developed and invented for the separation of single cell from the biological mixture that includes differential lysis, laser micro-dissection, cell sorting (FACS), sieve-based filtration, (vi) micro-fluidic devices or immunomagnetic beads cell separation of fresh samples, and the magnetic activated cell sorting (MACS).
Out of them, some techniques have been commonly applied for cell separation in forensic biology. Each technique has its own limitation. Some recent studies showed, magnetic activated cell sorting (MACS), laser capture microdissection (LCM), DEPArray technology and fluorescence activated cell sorting (FACS) has proved to be effective in separation of single cell from cell mixtures.
Therefore, in this review we have evaluated these four alternative methods and their potential application in the modern-day over the others for the separation of a single cell from the mixture. In this review we also discuss the advantage of these methods and their modern–day applicability and acceptance in the forensic world.
Chronic obstructive pulmonary disease (COPD) is associated with numerous comorbidities, including muscle involvement which consists of changes in the structure and function of peripheral and respiratory muscles. Ultrasound can provide a non-invasive assessment of muscle damage. Ultrasound assessment of the quadriceps contractility index (Qci) is feasible, rapid, simple, and reliable. Numerous studies have demonstrated that Qci is linked to the severity of COPD, clinical symptoms, and respiratory muscle activity. Furthermore, ultrasound makes it possible to observe the dynamics of the diaphragm by measuring its amplitude, its contraction speed, and the duration of each contraction phase. Ultrasound examination of muscle damage in COPD could constitute a promising new tool to assess the severity of the disease.
Oxygen therapy is the main supportive treatment in hypoxemic respiratory failure and has traditionally been delivered using low and high flow devices. However, the maximal flow rates that these devices can deliver are limited because of the insufficient heat and humidity provided to the gas administered. Low flow devices such as the nasal cannula, conventional face mask and reservoir bag deliver a flow rate of up to 15 L/min by administering more variable oxygen fractions (FiO2), depending on the patient’s respiratory pattern, peak inspiratory flow and characteristics of the devices. Conventional high flow devices, such as venturi type masks, utilize a constant flow of oxygen through precisely sized ports, entraining the ambient air, using the Bernoulli principle, providing a more constant inspired oxygen fraction. However, they are less tolerated than nasal cannulas because they are less comfortable and the insufficient humidification and heating of the gas delivered [1].
In the last two decades, new devices have been developed to administer high humidified and heated flow through a nasal cannula (HFNC) that also allows the delivery of oxygen with a known FiO2 up to 100%. In the literature, this technique has also been called mini CPAP (continuous positive airway pressure), transnasal insufflation, high nasal flow ventilation, high flow oxygen therapy, and high flow nasal cannula oxygen therapy [2].
It is considered that high flow nasal cannula has certain benefits compared to those of oxygen therapy previously detailed. HFNC manages a flow of more than 30 L/min, which is able to surpass the peak inspiratory flow of the patient, being able to reach values between 60-80 L/min depending on the flow used. The gas source, which may be delivered by an air/oxygen blender, fans, or a flow generating turbine, is connected by an active humidifier to a nasal cannula and the FiO2 can be adjusted independently of the flow.
From a clinical point of view, there is some confusion between venturi and high flow nasal cannula devices. In the literature, both have been considered as high flow oxygen therapy devices. In our opinion this is not appropriate because the high nasal cannula flow is much more than a simple system for administering oxygen therapy [3]. Venturi-type masks provide the patient with a gas mixture with a controlled FiO2, but do not exert additional benefits on the ventilator mechanics of the patient. Nevertheless, HFNC allows the delivery of a high flow, which can also add oxygen therapy, providing a series of physiological effects that imply an active treatment to respiratory failure.
Effects related to HFNC include the following:
1. Delivery of higher and more stable FiO2 values, because the flow delivered is greater than the patient’s inspiratory demand.
2. The anatomical dead space decreases by washing the nasopharynx, consequently increases alveolar ventilation. This improves the thoracoabdominal synchrony.
3. Respiratory work decreases because it acts as a mechanical stent in the airway and markedly attenuates inspiratory resistance.
4. The gas administered is warmed and humidified, improving mucociliar clearance, reducing the risk of atelectasis, improving ventilation perfusion and oxygenation ratio.
5. There is a CPAP-like effect. The dynamic positive espiratory airway pressure generated by HFNC reaches a value between 6-8cmH2o depending on the flow and the size of the cannula. This positive pressure distends the lungs and ensures their recruitment.
6. Pulmonary end-expiratory volume is higher with HFCN than with conventional high-flow oxygen therapy.
7. In addition, the technique is considered easy and simple for the medical staff and nurses, and can be used in different areas (emergency, hospitalization, critical care unit, weaning centers) and even at home [4].
Currently available evidence has demonstrated that HFNC therapy is an alternative for the treatment of acute hypoxemic respiratory failure, hypercapnic respiratory failure, acute heart failure, as rescue therapy preventive therapy in post-extubation respiratory failure and in specific conditions such as bronchoscopy [5].
We believe that high-flow nasal cannula treatment should not be confused with high flow oxygen therapy of venturi masks. According to detailed mechanisms of action, HFNC is not limited to being only an oxygen therapy system but also behaves as a true treatment that can be used in different clinical scenarios, generating physiological benefits that result in the reduction of respiratory work. In addition, in venturi type masks, the air is not humidified and complications such as dryness and nasal pain are common, generating a poor tolerance to oxygen therapy. The benefits of proper humidification and heating of the gas delivered with HFNC therapy allow better comfort and tolerance of the patient with easy adherence to the treatment. All this contributes to making HFNC be considered a technique of choice in patients with hypoxemic respiratory failure. The growth in its use associated with easy acceptance for patients and the expansion in its application show us that HFNC is a promising therapy.
Endometrial Stromal Sarcoma (ESS) is a rare gynecological malignancy originating from endometrial stromal tissue. Representing only a tenth of uterine malignant tumors, ESS is categorized into Low-Grade (LGESS) and High-Grade (HGESS) based on nuclear division. Interestingly, prognostic studies have found no strong correlation between ESS prognosis and nuclear division activity. Undifferentiated Uterine Sarcoma (UUS) represents a spectrum of tumors with varied morphological, clinical, and prognostic features, and lacks a standardized naming convention. In 2014, the World Health Organization grouped ESS into LGESS, HGESS, and UUS based on clinical and pathological attributes. HGESS, despite its rarity, is notorious for its poor prognosis and low survival rate. Its early detection is complicated due to its asymptomatic presentation and ambiguous pathogenesis, leading to debates over treatment approaches. This article delves into the recent research developments concerning HGESS.
Aims: To audit the use of cervical dilators, local anaesthetic, and failure rates in outpatient hysteroscopy over a two-year period in University Hospital Kerry. To review the experiences of women attending the outpatient hysteroscopy clinic (OHC) over a two-year period in University Hospital Kerry.
Methods: Retrospective data review was carried out. Green-top Guideline No. 59: Best Practice in Outpatient Hysteroscopy, published by the Royal College of Obstetricians and Gynaecologists (RCOG), was the standard used for comparison.
Results: Two hundred and twenty women were seen over a two-year period. The average age was forty-eight. The most common complaint being of menorrhagia/irregular bleeding per vaginum (PV).
Local anaesthetic was used in just under one third of cases of which half required cervical dilatation. Most women reported experiencing mild to moderate levels of discomfort however most would opt for an outpatient hysteroscopic procedure again if required.
Discussion/Conclusion: Outpatient hysteroscopy is a well-tolerated and safe procedure. Suitability for outpatient hysteroscopy is not predictable based on parity of menopausal status. Women would elect to undergo outpatient hysteroscopy again if required and this is likely due to several reasons including convenience and lack of requirement for general anaesthetic.
There is a constant rise in cases of rhino-orbital mucormycosis in people with Coronavirus disease 2019 (COVID-19). Generally, Mucormycosis develops in immunosuppression or debilitating diseases. In cases having head and neck involvement, the mold enters the respiratory tract with further involvement of nose and sinuses and there is consecutive progression into orbital and intracranial structures. Diabetes Mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. The clinical examination and direct smears are helpful for early diagnosis of the disease and timely intervention. For the better prevention and management of such opportunistic infections in COVID-19 patients, it is prudent to establish prophylactic treatment protocols along with rational use of corticosteroids. We here report a case of Rhino-orbital Mucormycosis infection caused by Rhizopus oryzae in a COVID-19 patient with Diabetes Mellitus.
Jorge Cabrera Morales*, Giuseppe Sias, Marco Manzoni and Giacomina Loriga
Published on: 5th October, 2023
“A 40-year-old woman with melanoma, under treatment with Dabrafenib and Trametinib, was evaluated in our hospital for rapidly progressive deterioration of renal function”. 8 months before the current admission, the patient had been diagnosed with melanoma, and underwent radical surgery and subsequent therapy with Dabrafenib and Trametinib.After 5 months of therapy, the patient was brought to this hospital for precordial pain, with a diagnosis of myopericarditis, therapy was started for heart failure with a good response. However, the patient developed a progressive impairment of renal function, associated with hemolytic anemia and thrombocytopenia. The peripheral smear showed the presence of schistocytes.The suspicion of atypical Hemolytic Uremic Syndrome (aHUS) was confirmed by the assay of C5B-9 induced by serum on endothelial cells, which showed a deposition of 331%, treatment with Eculizumab was initiated.After 3 administrations the patient did not improve, with further worsening of the hemolytic condition, and progression of renal damage.Due to the failure of Eculizumab, we considered the use of Ravulizumab. However, in Italy only can be administered to patients in Eculizumab stable treatment for at least three months. Nevertheless, faced with the catastrophic condition, it was decided to shift the therapy and use off-label Ravulizumab. After 10 days of the first administration, the laboratory tests showed a continuous rise in the values of haptoglobin, platelets, and hemoglobin, and a decrease in LDH. The renal function failed to return to normal values but after 20 days of therapy with Ravulizumab, there was complete resolution of the hemolytic condition.
Background/Introduction: WHO recommended ‘ready to use therapeutic food’ (RUTF) for community-based management (CMAM) of severely malnourished children (SMC). This is often rejected by children. The objective is to identify and map the locally produced and socio-culturally acceptable food items to treat SMC. Methods: Through community participation, eight varieties of MAHAN Local therapeutic foods (LTFs) were prepared by tribal females at our center as per WHO norms with a shelf life of 4 weeks. LTFs with micronutrients were given at the feeding centers in the villages under supervision 3 - 4 times a day. Results: Multiple, palatable, culturally acceptable, safe, feasible with local womanpower, and cost-effective recipes were developed. Hence, our LTFs are qualitatively superior to other therapeutic foods. This mapping exercise provides a ready reference to other government or non-government organizations for CMAM. Conclusion: MAHAN-LTF is a multiple, palatable, generalizable, and sustainable therapeutic food and are being used in other tribal blocks of India.
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