PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.

Idiopathic Pulmonary Fibrosis Comorbid With Mediastinal Small Cell Carcinoma: A Clinical Dilemma.

We present an interesting case of mediastinal small cell carcinoma (MSCC), an exceedingly rare entity, comorbid with idiopathic pulmonary fibrosis (IPF). A 66-year-old female was first seen in the pulmonology office for abnormal chest computed tomography (CT) findings of right apical bronchiectasis and subpleural fibrotic changes with focal pleural thickening along the fissures, along with a right lower lobe nodule. Pulmonary function testing (PFT) showed an obstructive pattern with modest bronchodilator response, although subsequent PFT showed a worsening restrictive pattern with a worsening DLCO. On a follow-up CT one year later, a soft tissue density with peripheral calcification was found in the anterior mediastinum, later found to be hypermetabolic on a PET scan. Radiographically, fibrosis worsened with the appearance of worsening diffuse bilateral coarse reticular interstitial changes with lower lobe predominance, honeycombing, and areas of ground-glass opacity. A biopsy of the mediastinal lesion showed a high-grade neuroendocrine tumor. Cam5.2, insulinoma-associated protein-1, synaptophysin, and thyroid transcription factor-1 immunostains were positive. She underwent four cycles of chemotherapy with cisplatin and etoposide with a total of 60 Gy of radiation. Mediastinal mass started to decrease in size. Her respiratory status, imaging, and PFTs continued to show evidence of IPF progression. Prednisone resulted in modest clinical and radiographic response. Steroid-sparing therapy with mycophenolate mofetil, although effective, had to be discontinued due to GI bleeding. Anti-fibrotic therapy was deferred due to evidence showing a lack of clinical improvement. We discuss the existing evidence available on IPF management and proceed to highlight the deficiencies in existing data available on the management of IPF and MSCC in these patients. Most of the cases of MSCC reported in the past have managed MSCC using guidance from treatment practices for small cell lung cancer. No reported cases discuss or describe the management of IPF and MSCC in the very rare cohort of patients our case represents.

Sweet Syndrome With Vasculitis: Time To Adopt a New Criteria?

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. Although perceived to be rare, the disease may well have been underreported due to lack of exposure in low-volume clinical settings and due to the use of rather strict clinical criteria for diagnosis. It presents as cutaneous papules, plaques, or nodules in an asymmetric distribution that follows fever and flu-like symptoms. Data on the disease is ever-expanding. Several associations have been identified, including drugs, infections, malignancies, and autoimmune diseases. Different disease patterns and histological variants have been identified. Pathophysiology is complex and multifactorial but appears to involve mechanisms that negatively influence neutrophil apoptosis and facilitate neutrophil recruitment. The existing diagnostic criteria exclude cases with vasculitis; over time, cases of neutrophilic dermatoses with vasculitis have been reported as SS as long as other criteria were met. Newer diagnostic models have been proposed, some arguing against the exclusion of vasculitis. Steroids continue to be the mainstay of treatment, and steroid responsiveness continues to be a part of the diagnostic criteria, although newer treatment modalities have been used and have shown promise. No established guidelines exist for management. We present a case of Idiopathic SS with vasculitis along with a brief review of the existing literature. We agree to the inclusion of vasculitis as proposed by the newer diagnostic criteria.

A Case of Mirtazapine-Induced Pancreatitis.

Acute pancreatitis is a concerning cause of hospitalization in the United States, with the most common etiologies being secondary to alcohol abuse and gallstones. Rarely, medications can trigger this inflammatory response, whether via direct toxic effects or other metabolic derangements. Mirtazapine is an antidepressant that has been associated with elevations in triglyceride levels on initiation. Relatedly, high triglyceride levels and autoimmune disorders are other causes of pancreatitis exacerbations. Here, we present the case of a female who was started on mirtazapine therapy and found to have elevated triglyceride levels. The course was complicated by acute pancreatitis requiring plasmapheresis, despite medication discontinuation, to which she responded well.

COVID-19 Vaccine Booster-Induced Dermatographism.

The urgent requirement for a preventative vaccination became more pressing due to the severe repercussions that the SARS-CoV-2 (COVID-19) virus had on society and the economy. The deployment of the COVID-19 vaccination program had to be expedited. As with all vaccinations, adverse events have been recorded with the COVID-19 vaccine. Some patients may experience cutaneous reactions such as rashes, itching, hives, and swelling after receiving the COVID-19 vaccine, but it is unclear how common these events are or how frequently they recur. This article discusses an unusual case of a young man who got chronic severe dermatographism after receiving a booster shot of the Moderna vaccine (Moderna, Inc., Cambridge, Massachusetts).

COVID-19 Vaccine-Induced Parsonage-Turner Syndrome: A Case Report and Literature Review.

All modern vaccines share the risk of neurological adverse effects. Only a few cases of Parsonage-Turner syndrome (PTS), an uncommon peripheral nerve condition associated with coronavirus disease 2019 (COVID-19) immunization, have been reported to date. We describe a case of COVID-19 vaccine-induced PTS and provide a brief literature review. A 78-year-old male non-smoker with a medical history of coronary artery disease presented with non-exertional, constant chest pain for one hour and new onset of bilateral hand weakness for three days. He had no neurological disease or allergies and denied any recent trauma or infection. Three weeks before the onset of the symptoms, the patient received a second dose of the BNT162b2 COVID-19 vaccine, which was administered 21 days after the first dose. Physical examination was significant for weakness in right-hand grip and wrist flexion. There were no other motor deficits, upper motor neuron signs, bulbar weakness, or sensory deficits. Diagnostic workup for the underlying diabetes mellitus, infections, or other autoimmune diseases was negative. Imaging workup revealed no demyelination, fracture deformity, traumatic subluxation, or compressive myelopathy. Nerve conduction studies, including needle electromyography, showed decreased motor unit recruitment in the bilateral first dorsal interosseous and right deltoid, biceps, and triceps muscles confirming PTS. The patient was treated with 40 mg/day of oral prednisone and occupational therapy to maintain range of motion and activities of daily living. PTS is also known as neuralgic amyotrophy, brachial plexus neuritis, brachial plexopathy, and shoulder-girdle syndrome. It is characterized by asymmetrical, chronic, resistant upper extremity neuropathic pain and neurological defects such as paralysis and paresthesia. There are two different types of PTS: non-hereditary and inherited. The etiology and pathophysiology of PTS are not fully understood. Various aspects such as genetic, environmental, and immunological predisposition may play a role in developing the syndrome. Infections, vaccines, and injuries are typical causes of non-hereditary forms. After the COVID-19 epidemic and the commencement of a global immunization effort, similar instances happened. Presently there is no available test that unequivocally confirms or excludes PTS itself. Electrodiagnostic study and imaging modalities help to rule out other differential diagnoses. Also, there is no specific treatment available; however, it may resolve independently of treatment with supportive care.

Myelomatous Pleural Effusion: A Rare Occurrence in Multiple Myeloma.

Various factors can cause pleural effusion in multiple myeloma patients. Myelomatous pleural effusion (MPE) is an uncommon but potentially life-threatening complication of multiple myeloma with a poor prognosis. After ruling out all other probable causes, the present case reports MPE in a patient with IgG kappa multiple myeloma.

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer / 药物分析学报

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast cancer has become increasingly challenging owing to the increase in tumor het-erogeneity and aggressiveness,which gives rise to therapeutic resistance.Epidemiological,population-based,and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer.Diallyl disulfide(DADS)and diallyl trisulfide(DATS)are the main allyl sulfur compounds present in garlic,and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation,tumor metastasis,and angiogenesis.The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer.This review discusses the potential anticancer activities of DADS and DATS,with emphasis on drug resistance in triple-negative breast cancer(TNBC).Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mecha-nisms of TNBC,especially in clinical studies.

Diffuse Alveolar Hemorrhage With Avelumab Maintenance Therapy.

Immune checkpoint blockade is a rapidly expanding therapeutic modality in oncology. However, its adverse effects extend beyond the cytotoxicity of conventional chemotherapy. Pneumotoxicity associated with immune checkpoint therapy presents a diagnostic conundrum that has been further complicated by the COVID-19 pandemic. We report a case of a patient with metastatic urothelial carcinoma who developed diffuse alveolar hemorrhage (DAH) following treatment with avelumab.

Efficient Data Communication Using Distributed Ledger Technology and IOTA-Enabled Internet of Things for a Future Machine-to-Machine Economy.

A potential rise in interest in the Internet of Things in the upcoming years is expected in the fields of healthcare, supply chain, logistics, industries, smart cities, smart homes, cyber physical systems, etc. This paper discloses the fusion of the Internet of Things (IoT) with the so-called "distributed ledger technology" (DLT). IoT sensors like temperature sensors, motion sensors, GPS or connected devices convey the activity of the environment. Sensor information acquired by such IoT devices are then stored in a blockchain. Data on a blockchain remains immutable however its scalability still remains a challenging issue and thus represents a hindrance for its mass adoption in the IoT. Here a communication system based on IOTA and DLT is discussed with a systematic architecture for IoT devices and a future machine-to-machine (M2M) economy. The data communication between IoT devices is analyzed using multiple use cases such as sending DHT-11 sensor data to the IOTA tangle. The value communication is analyzed using a novel "micro-payment enabled over the top" (MP-OTT) streaming platform that is based on the "pay-as-you-go" and "consumption based" models to showcase IOTA value transactions. In this paper, we propose an enhancement to the classical "masked authenticated message" (MAM) communication protocol and two architectures called dual signature masked authenticated message (DSMAM) and index-based address value transaction (IBAVT). Further, we provided an empirical analysis and discussion of the proposed techniques. The implemented solution provides better address management with secured sharing and communication of IoT data, complete access control over the ownership of data and high scalability in terms of number of transactions that can be handled.

Co-administration of Aluminum Sulfate and Propolis Regulates Matrix Metalloproteinases-2/9 Expression and Improves the Uterine Leiomyoma in Adult Rat Model.

The aim of this study was to evaluate the effects of aluminum sulfate (alum) with propolis (PR) on uterine leiomyoma (UL) in rat model. One hundred and four female Wistar rats (180-200 g) were allocated into two main groups of control (Co, n = 8) and experiment (UL model [estradiol benzoate 200 µg/kg/IM twice/week/8 weeks] with/without treatment) defined in 13 subgroups with/without treatment with coil oil (UL + COi), PR (100 or 200 mg/kg) as UL + PR100 or 200, alum (35, 75 or 150 mg/Kg) as UL + AL 35, 75, or 150, and PR (100 mg/kg or 200) with alum (35, 75, or 150 mg/Kg) as UL + PR100 or 200 + AL35, 75, or 150. Subgroups received doses of therapeutics for 14 days (IP). In the end, rats were sacrificed, and the uteri were isolated for molecular and histopathological investigations. The myometrium thickness, collagen contents, and gene expression of MMP-2 and 9 increased significantly in experimental groups with/without treatment (P Ë‚ 0.05). PR administration (100 and 200 mg/kg) alone or with alum (35 and 75 mg/kg) significantly decreased myometrium collagen contents and the gene expression and protein concentration of MMP-2 and 9 compared with UL and UL + Coi subgroups (P Ë‚ 0.05). Alum (75 mg/kg) with PR (200 mg/kg) could improve UL features and reduce MMP-2 and 9 gene expression.

Diagnostic Yield of Ultrasound-guided Trucut Biopsy in Diagnosis of Peripheral Lung Malignancies.

Introduction While computed tomography (CT) guided lung biopsy has been standard in histological diagnosis of pulmonary lesions, its use is limited to the interventional radiologists only. Ultrasound (US) guided biopsy of pulmonary lesions, which can be performed in-clinic by the pulmonologists only, is becoming a more popular technique. It also has the edge of real-time techniques, multi-planar imaging, and no radiation exposure to the patients. Methods This is a retrospective review of all the patients presenting with pleural-based lung lesions who underwent US-guided biopsy for diagnosis in the Department of Pulmonology, Liaquat University of Medical and Health Sciences Hospital, Hyderabad, Pakistan from 1st January 2013 till 31st December 2017. The diagnostic yield, sensitivity, specificity, and accuracy of US-guided biopsies were evaluated for diagnoses of peripheral lung malignancies. Results Ultrasound-guided biopsies for lung lesions has a diagnostic yield of 88.3%, sensitivity of 95.80%, and specificity of 90% with an accuracy of 95.35%. Pneumothorax as an immediate complication was seen only in 1.5% cases. Conclusion US-guided biopsies are a much safer diagnostic alternative to CT-guided biopsy for lung lesions and have high diagnostic yield. It doesn't require special radiological interventionists, can be performed at patients' bedsides, and the equipment is not as expensive.

Bone Marrow Stromal Cells with the Granulocyte Colony-Stimulating Factor in the Management of Chemotherapy-Induced Ovarian Failure in a Rat Model.

BACKGROUND: Bone marrow stromal cells (BMSCs), as a type of mesenchymal stem cells, and the granulocyte colony-stimulating factor (G-CSF), as a type of growth factor, may recover damaged ovaries. The aim of the present study was to investigate the effects of the coadministration of BMSCs and the G-CSF on damaged ovaries after creating a chemotherapy model with cyclophosphamide (CTX) in rats. METHODS: The present study was performed in Semnan, Iran, in the late 2016 and the early 2017. BMSCs were cultured and were confirmed using the CD markers of stromal cells. Forty female Wistar rats were randomly divided into 4 groups. The rats were injected intraperitoneally with CTX for 14 days to induce chemotherapy and ovarian destruction. Then, the BMSCs were injected into bilateral ovaries and the G-CSF was injected intraperitoneally, individually and together. Four weeks later, the number of ovarian follicles using H&E staining, the number of apoptotic granulosa cells using the TUNEL assay, the number of produced oocytes from the ovaries, and the levels of serum E2 and FSH using an ELISA reader were assessed. Statistical analysis was done using one-way ANOVA with SPSS, version 16.0. RESULTS: The results showed that the effects of the coadministration of 2×106 BMSCs and 70 µg/kg of the G-CSF were significantly more favorable than those in the control group (P<0.001), the BMSC group (P=0.016), and the G-CSF group (P<0.001) on the recovery of damaged ovaries. CONCLUSION: The efficacy of the coadministration of BMSCs and the G-CSF in the recovery of ovaries damaged by chemotherapy was high by comparison with the administration of either of them separately.

Atrial fibrillation among adult Saudi patients with chronic heart failure: Tertiary center experience.

OBJECTIVE: To estimate the rate of atrial fibrillation (AF) among adult patients with chronic heart failure (HF) from Saudi Arabia, and to identify the clinical and the demographic characteristics. METHODS: This study was performed using all medical records of patients registered in Prince Sultan Cardiac Center in Qassim, Saudi Arabia, and diagnosed with HF during the period from January 1, 2010 to June 30, 2014. The review process included patients diagnosed with chronic HF who were registered for follow-up during the study period. The rate of AF was calculated, and the associated risk factors were determined. RESULTS: The rate of AF among chronic HF (n = 70) patients was 14.9%. The rate of AF was higher among males (15.7%) than females (12.5%). In both genders, the rate of AF rose with advancing age, and in each age stratum, it was higher in males than females. The rate of AF was higher if chronic HF was associated with chronic diseases, such as diabetes mellitus (DM, 14.3%), hypertension (HTN, 20%), and none of the patients had a history of chronic kidney disease. CONCLUSION: The rate of AF with chronic HF is high among Saudi Arabia patients. It is higher among male patients and HTN and DM patients.

Effect of quercetin on the number of blastomeres, zona pellucida thickness, and hatching rate of mouse embryos exposed to actinomycin D: An experimental study.

BACKGROUND: Quercetin is a flavonoid with the ability to improve the growth of embryos in vitro, and actinomycin D is an inducer of apoptosis in embryonic cells. OBJECTIVE: The aim was to evaluate the effect of quercetin on the number of viable and apoptotic cells, the zona pellucida (ZP) thickness and the hatching rate of preimplantation embryos exposed to actinomycin D in mice. MATERIALS AND METHODS: Two-cell embryos were randomly divided into four groups (Control, Quercetin, actinomycin D, and Quercetin + actinomycin D group). Blastocysts percentage, hatched blastocysts, and ZP thickness of blastocysts was measured. The number of blastomeres was counted by Hoechst and propidium iodide staining and the apoptotic cells number was counted by TUNEL assay. RESULTS: The results showed that the use of quercetin significantly improved the growth of embryos compared to the control group (p=0.037). Moreover, quercetin reduced the destructive effects of actinomycin D on the growth of embryos significantly (p=0.026). CONCLUSION: quercetin may protect the embryos against actinomycin D so that increases the number of viable cells and decreases the number of apoptotic cells, which can help the expansion of the blastocysts, thinning of the ZP thickness and increasing the hatching rate in mouse embryos.

The efficacy of local infiltration of triamcinolone acetonide with lignocaine compared with lignocaine alone in the treatment of postherpetic neuralgia.

OBJECTIVE: To assess the efficacy of local infiltration of corticosteroid with lignocaine compared to lignocaine alone in the treatment of postherpetic neuralgia. DESIGN: A randomized clinical trial. PLACE AND DURATION OF STUDY: The Skin Department, Military Hospital, Rawalpindi from September 2002 to March 2003. PATIENTS AND METHODS: Sixty patients were selected for the study. They were randomly assigned to two groups. Group-I received injection triamcinolone acetonide with lignocaine and group-II was given injection lignocaine alone. Three injections were given to each patient at fortnightly interval and pain relief was assessed by visual analogue scale at 6 and 12 weeks following the first injection. RESULTS: Follow-up at 6 weeks showed complete pain relief in 63.3% (n=19) patients of group-I in comparison to 16.6% (n=5) of group-II. Chi-square value was 13.3 (p<0.001). At 12 weeks follow-up group-I showed further improvement with complete pain relief in 83.3% (n=25) whereas group-II showed diminishing response with cure rates falling to 6.6% (n=2). Chi-square value was 35.6 (p<0.001). CONCLUSION: Locally infiltrated injection triamcinolone acetonide with lignocaine was significantly more effective than injection lignocaine alone in the treatment of postherpetic neuralgia both at 6 and 12 weeks follow-up.