Metastatic Angiosarcoma: A Rare Malignancy

Angiosarcoma is an infrequent vascular malignancy with grave prognosis due to distant metastasis at initial presentation. The predominant metastatic sites of angiosarcoma are lung; and it is particularly important and should be approached with multimodality treatment because pulmonary metastasis of angiosarcoma frequently induces severe complications. Here, we reported a case of angiosarcoma in an old Indian male presented with cough and hemoptysis. 18-FDG PET-CT scan revealed multiple organ involvement by tumor, and excisional biopsy from lung and pleural nodule revealed malignant tumor composed of spindle shaped epithelioid cell. Strong positivity for D2-40, CD 31 & CD 34 favoured the diagnosis of angiosarcoma. Patient was planned for intravenous chemotherapy with paclitaxel along with zoledronic acid. After 3-cycles of chemotherapy, re-evaluation with PET-CT revealed good response. In view of stable disease, it was planned to continue the same regimen for three more cycles. However, after receiving two more cycles of chemotherapy, patient’s condition deteriorated rapidly and died within a month. The present case showed, paclitaxel has a good impact on metastatic angiosarcoma to diminish lung nodules. However, more effective treatment regimen should be explored to effectively treat metastatic angiosarcoma and increase survival.

Prospects for using low-dose radiation in the complex therapy for COVID-19

This review presents the literature data of new approaches for the treatment of COVID-19 with low doses of radiation (LDR). In addition, data on the use of LDR for the treatment of various disorders, in particular pneumonia, a number of inflammatory processes of various etiology, as well as Alzheimer’s disease are discussed. The mechanisms of LDR action are briefly described, associated with the activation of the immune system and antiinflammatory response due to the effect on the processes of oxidative stress, which is reflected in an increase in the activity of cytokines (interleukin- (IL-) 6), changes in the expression of a number of genes (such as P53 and NF-κB (p65)) and long non-coding RNAs (ncRNAs) (the authors’ own data are presented). Based on the analysis of the material presented, it can be assumed that further clinical trials of the effect of MDR (5–10 cGy) on patients with COVID-19, who are at different stages of the disease, will reveal the optimal conditions for the development and use of an effective treatment regimen.

Bevacizumab-associated implant presence-triggered osteonecrosis: A case report and literature review

The effect of bevacizumab-related osteonecrosis of the jaw on previously osseointegrated dental implants has not been adequately studied. Here, we report a case of osteonecrosis of the jaw detected around dental implants placed prior to bevacizumab therapy. A 66-year-old woman undergoing bevacizumab therapy for metastatic triple-negative breast cancer, developed malocclusion following buccal gingival swelling and pain in the #18, #19, and #20 tooth region. The patient visited a local dental clinic, where existing implants in relation to #19 and #20 were removed. Subsequently, the patient visited our department, and intraoral examination revealed necrotic bone in the region corresponding to #19 and #20. Radiographic examination showed a pathological fracture in this region that was considered to result from osteonecrosis of the jaw. Bevacizumab therapy was suspended temporarily till the acute inflammation had subsided. In addition, treatment with antibacterial agents and conservative surgery was considered. Complete soft tissue coverage was observed 14 days following surgery. In recent years, the number of patients receiving bevacizumab treatment has increased. Since bevacizumab-related osteonecrosis of the jaw could occur around previously osseointegrated dental implants as well, this case report suggests an effective treatment regimen based on a combination of antibacterial agents and conservative surgery.

Effect of Spider Therapy on Motor Functions and Balance in Cerebral Palsy - An Evidence Based Study

Background: Cerebral palsy describes a group of disorders of development of movement and posture, causing activity limitation, that are attributed to non- progressive disturbances that occurred in developing fetal or infant brain. Spider therapy is an intensive treatment approach which was originally developed in Poland. It involves suspending the child in the Centre of universal exercise unit by using a number of elastic bungee cords of different elasticity. These cords are attached to specific points on special belt around the child’s waist, forming a unique spider web around the child which provides them essential support. Purpose: The purpose is to study the scientific evidences regarding the effect of the spider therapy on motor functions and balance in cerebral palsy Methodology: A search for relevant articles was carried out using key words- cerebral palsy, spider therapy, motor functions and balance and search engines-Google Scholar, PubMed, PEDro, Science Direct, Research Gate and CINAHL. Studies were selected from year 2005-2020. eleven studies were included in which there were 1 Meta-analysis, 2 Systematic reviews and 4 Randomized controlled trials,1Quasi- Experimental study, 1 case study, 1 interventional study and 1 retrospective study. Results: 11 studies were reviewed from which 6 studies concluded that spider therapy is more effective than a control group receiving conventional treatment, 2 study highlighted MFR to be equally effective to alternative treatment and 3 studies concluded that spider therapy have significant but small effects on functioning at post-treatment and follow-up Conclusion: Based on the analysis of these 11 articles, it can be concluded that spider therapy is an effective treatment regimen in cerebral palsy. Clinical Implication: Spider therapy is found to be effective in improving balance and motor functions in s cerebral palsy, therefore spider therapy can be considered as an adjunctive treatment in cerebral palsy. Keywords: cerebral palsy, spider therapy, motor functions and balance.

Pharmacological Treatment for the Management of COVID 19: A Narrative Review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is alarming worldwide incurring tremendous loss of life and possession. Individuals are facing a terrible pandemic condition in the absence of appropriate medicines and vaccines to combat SARS-CoV-2 infection. This review aimed to provide details on potential treatment steps that can be taken in the current pandemic-fighting situation in Nepal. A massive review was performed including 60 articles from the relevant field. Preliminary results on the efficacy of some existing anti-viral agents were found, however, promising data on effective treatment regimen for COVID 19 are yet to be obtained. This review examines various drugs and their mechanism of actions which are currently used in clinical trials or may be used to treat COVID-19 in the near future.

Effect of Myofascial Release Technique in Plantar Fasciitis on Pain and Function- An Evidence Based Study

Background: Plantar fasciitis is a common cause of pain in the heel which occurs as a result of inflammation of the plantar aponeurosis at its attachment on the calcaneal tuberosity. Myofascial Release Technique is intended to improve the mobility of soft tissue through application of a slow, controlled mechanical stress directly into a restriction. Pressure is gradually increased or repeated until the mobility of the tissue is felt to improve. Purpose: The purpose is to study the scientific evidences regarding the effect of the myofascial release technique in plantar fasciitis. Methodology: A search for relevant articles was carried out using key words- plantar fasciitis, myofascial release technique, pain and function and search engines- Google Scholar, PubMed, PEDro, ScienceDirect, ResearchGate and CINAHL. Studies were selected from year 2010-2019. Ten studies were included in which there were 7 RCT, 1 Prospective experimental study, 1 Quasi Experimental study and 1 Pre-post interventional study. Results: 10 studies were reviewed from which 7 studies concluded that MFR is more effective than a control group receiving sham treatment or conventional treatment and 3 studies highlighted MFR to be equally effective to alternative treatments. Conclusion: Based on the analysis of these 10 articles, it can be concluded that MFR is an effective treatment regimen in individuals with Plantar Fasciitis. Clinical Implication: MFR is found to be effective in reducing pain and improving functions in individuals with plantar fasciitis, therefore MFR technique can be considered as an adjunctive treatment in plantar fasciitis. Keywords: Plantar Fasciitis, Myofascial Release Technique, Pain, Function.

A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies.

7012 Background: Isocitrate dehydrogenase-1 ( IDH1+) mutations are present in 5-15% of myeloid malignancies, promoting leukemogenesis through production of the oncometabolite 2-hydroxyglutarate resulting in arrested myeloid differentiation. IDH1+ malignancies demonstrate increased reliance on the anti-apoptotic protein BCL-2, enhancing susceptibility to the BCL-2 inhibitor venetoclax (VEN). We report an interim safety and efficacy analysis of the IDH1 inhibitor ivosidenib (IVO; 500 mg PO daily D15-continuous) combined with VEN (D1-14) +/- azacitidine (AZA; 75mg/m2 D1-7 every 28 days). Methods: Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed AML (ND: treatment naïve [TN] or secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA). Primary objectives included safety and tolerability, and IWG defined overall response (ORR: CR+CRi+CRh+PR+MLFS). Prior receipt of IVO or VEN was exclusionary. Results: 25 evaluable patients (DL1: 6, DL2: 6, DL3: 13) enrolled with a median follow-up of 16.1 months. Median age was 67 (range: 44-84). 84% (N=21) of patients had AML (ND: N=13 [TN: 8, sAML: 5], R/R: N=8), while 16% (N=4) had MDS. ELN risk was intermediate and adverse in 16% (N=4) and 56% (N=14). Median IDH1 VAF at enrollment was 22.7% (range: 5.1%-47.8%). Two patients had received a prior IDH1 inhibitor. The ORR was 92% (DL1: 67%, DL2: 100%, DL3: 100%). Composite CR (CRc: CR+CRi+CRh) was 84% (DL1: 67%, DL2: 100%, DL3: 85%) including 92% (TN: 100%, sAML: 80%), 63%, and 100% of patients with ND-AML, R/R-AML, or MDS. Median number of cycles received was 4 (DL1: 8.5, DL2: 6, DL3: 4) with ongoing responses in 62% (DL1: 33%, DL2: 50%, DL3: 82%) at 1-year. 8 patients transitioned to SCT (DL1: 0, DL2: 2, DL3: 6), and 8 patients remain on study (DL1: 2, DL2: 1, DL3: 5). 1-year OS was 68% for the entire study population (DL1: 50%, DL2: 67%, DL3: 78%), 71% in ND-AML (TN: 86%, sAML: 60%), 50% in R/R-AML, and 100% in MDS. Measurable residual disease negative CRc by multiparameter flow cytometry was attained in 60% (ND-AML: 67%, R/R-AML: 60%, MDS: 33%) correlating with improved OS (median OS: NR vs. 8.5 months, p-value: 0.038). Common grade 3/4 adverse events included febrile neutropenia (28%) and pneumonia (24%). Tumor lysis and differentiation syndrome occurred in two and four patients; all cases resolved with medical management. Conclusions: IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+myeloid malignancies. The combination therapy is associated with an acceptable and expected toxicity profile with notable efficacy and high rates of MRD-negative CRc in AML. Enrollment into the study continues. Clinical trial information: NCT03471260. [Table: see text]

Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza

Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.

Marfan syndrome in combination with severe atopic dermatitis: importance of early diagnosis and treatment of patients with allergic dermatitis in childhood

We report a case of a rare combination of Marfan syndrome and severe atopic dermatitis (AD) in a 32-year-old male patient. He developed AD in early childhood and then had a relapse at the age of 18 years caused by stress. After this, AD became severe due to stress associated with aortic aneurysmectomy. The patient also had side effects caused by steroids, including multiple pustular eruptions, Kaposi's varicelliform eruption, edema and hyperemia of the periorbital area, pain and swelling of the small joints of the hands. These side effects, as well as specific cardiovascular symptoms typical of Marfan syndrome necessitated the search for alternative treatment strategies for severe AD. Eventually, we managed to find an effective treatment regimen that caused no side effects or adverse events, while the symptoms subsided. This case demonstrates the importance of early AD diagnosis in childhood in order to prevent its transition into severe chronic form that can hardly be managed in adulthood. Key words: atopic dermatitis, children, diagnostic criteria, clinical manifestations, hereditary diseases, Marfan syndrome

Failure of multiple surgical procedures and adjuvant chemotherapy in early-stage steroid-cell ovarian tumor treatment: a case report and literature review

Ovarian steroid-cell tumors (SCTs) are a rare subgroup of sex-cord tumors of the ovary, accounting for less than 0.1% of all ovarian tumors. Not otherwise specified (NOS) tumors are the most common subtype. More than half of patients with SCTs-NOS show hyperandrogenic symptoms. The primary treatment for SCTs is surgery, as most cases are early-staged and benign. Because of the low incidence of metastatic disease, there is insufficient reliable information on the role of adjuvant therapy and the most effective treatment regimen. In this report, a rare case of a recurrent SCT-NOS in a 36-year-old female patient without endocrine symptoms is presented, highlighting the significance of appropriate pathological evaluation and immunohistochemical testing for the accurate diagnosis of this malignancy, particularly in the case of hormonally “silent” tumors. The metastatic tumor described here showed no response to four courses of adjuvant chemotherapy after several debulking surgeries. Based on the clinical findings, the neoplastic etiology should always be considered during the resection of ovarian tumors to prevent possible disease dissemination due to inappropriate surgical techniques.