COVID-19 Thrombosis: Bridging the Old and New Concepts.

The coronavirus disease 2019 (COVID-19) pandemic is an evolving condition in the absence of established treatment and vaccines. The few autopsy studies on COVID-19 patients suggested the presence of pulmonary microvascular thrombosis. Hence, it is imperative to understand the pathobiology of thrombus formation and speculate the therapeutic goals in combating COVID-19. This paper focuses on a holistic approach by integrating the previous concepts and current concepts of thrombosis to better understand the pathogenesis of thrombosis.

A Comparative Study Of Concurrent Chemo-Radiotherapy With or Without Neoadjuvant Chemotherapy in Treatment of Locally Advanced Non Small Cell Lung Cancer.

INTRODUCTION: The standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy. This study was undertaken to evaluate whether induction chemotherapy along with concurrent chemoradiotherapy would result in better tumor control, improved symptom control and any variation in toxicity as compared to concurrent chemoradiotherapy alone. PATIENTS AND METHODS: Between February 2015 to September 2016, 25 patients each were randomized to control group, in which they received concurrent chemoradiotherapy with weekly cisplatin 40 mg/m2 intravenous, during chest radiotherapy of 66Gy in 33 fractions for 6.5 weeks, and study group, in which patients received three cycles of induction chemotherapy with Cisplatin 75 mg/m2and Paclitaxel 175 mg/m2administered every 21 days followed by identical chemoradiotherapy. RESULTS: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, histology, grade, and stage. At 6thmonth follow-up, complete response was seen in 6 patients in control arm and 7 patients in study arm (?2 = 1.603, p = 0.205) and partial response was seen in 13 and 12 patients in control and study arms respectively (?2 = 1.932, p = 0.165). Symptom control of cough, hemoptysis, chest pain and dyspnoea were also similar in both groups. DISCUSSION: In our study, no difference in treatment outcome with respect to the two groups was observed, which was similar to studies which have been conducted previously. Radiation is a good modality for symptom control of cough, hemoptysis, chest pain and dyspnoea. In toxicities, pneumonitis and hematological toxicity was slightly higher in study group even at 6th month follow up. CONCLUSION: Slight increase in toxicity with no added benefit in locoregional tumor control and symptom regression, was seen in patients receiving induction chemotherapy followed by chemoradiotherapy. Concurrent chemoradiotherapy alone can thus be used as only modality of treatment in unresectable stage III NSCLC.

Risk stratification of systemic reactions to subcutaneous immunotherapy: A retrospective study.

Background: Subcutaneous allergen immunotherapy (SCIT) is a very effective treatment modality; however, it can be associated with both local and systemic reactions (SR). Identifying patient factors that predict SR remains paramount. Objective: Our aim was to identify the rate of SRs to SCIT as well as identify patient risk factors associated with the development of SRs. Methods: We conducted an institutional review board approved 10-year retrospective chart review of 459 patients who received SCIT in our clinic. The patients were placed into cohorts according to age, which included pediatric (5-18 years), adult (19-64 years), and senior (>65 years) patients. Results: An SR (N = 177) was identified in 24.8% of the patients (n = 114). The incidence of SR per injection was 0.2% (177 SRs of 74,183 total injections). SRs were identified as class 1 (n = 152), class 2 (n = 21), class 3 (n = 2), and class 4 (n = 2) according to the 2010 World Allergy Organization's SR grading system. There were no observed differences in the number of SRs with respect to age group. Female patients were more likely to have an SR (p = 0.02) overall as well as more than one reaction (p = 0.002). Other risk factors included the following: a patient-reported history of food allergy (p = 0.05), drug allergy (p = 0.005), or positive skin test result to cat and/or dog (p = 0.01). In addition, patients who were receiving SCIT to cat and/or dog (p = 0.004) or to dust mite (p = 0.03) were more likely to have an SR. Conclusion: In our patient population, the majority of SRs to SCIT occurred in female patients, patients with a history of drug or food allergies, and those who were receiving pet or dust-mite SCIT.

C1-esterase inhibitor (Cinryze®) use in the treatment of pediatric hereditary angioedema.

Hereditary angioedema (HAE) is a rare genetic disease resulting in unpredictable and potentially life-threatening subcutaneous and submucosal attacks mediated by the vasoactive peptide, bradykinin. HAE often presents within the first or second decade of life, with attacks increasing in both frequency and severity over time. First-line therapies exert their action by replacing C1 inhibitor (C1-INH) or via blocking the production or function of bradykinin. Cinryze® is a nanofiltered C1-INH, approved in Europe for the acute treatment, preprocedure prevention and routine prophylaxis of HAE attacks, and for routine prophylaxis of attacks in the USA. Of the current C1-INH preparations available, Cinryze shows particular promise in the safe and effective treatment and prophylaxis of HAE attacks in pediatric age patients.

Pneumococcal 13-valent conjugate vaccine administration after inferior response to pneumococcal vaccine.

BACKGROUND: The pneumococcal vaccine, a nonconjugated vaccine, may be used to evaluate the integrity of the humoral immune system. Those patients with an inferior response to a nonconjugated vaccine may be vaccinated with a conjugated vaccine, which elicits both a B- and T-cell response. OBJECTIVE: We evaluated the immunogenicity of a conjugated vaccine in patients with inferior responses to a nonconjugated vaccine. METHODS: This was an institutional review board approved retrospective study that involved 22 patients with suspected specific antibody deficiency who received a nonconjugated vaccine, followed by a conjugated vaccine. Patients with an inferior response had <70% response in pneumococcal serotypes (1.3 µg/mL, with at least a two to fourfold increase), whereas protective responses were those with a >70% response. These patients were subsequently administered a conjugated vaccine at various time intervals (1-36 months), and titers were evaluated 4-6 weeks later. RESULTS: A protective response was found in 6 of 22 patients (average age, 62.2 years) after conjugated vaccine administration. Half of the responders were vaccinated <12 months after nonconjugated vaccine administration. The majority of the nonresponders (n = 16) received a conjugated vaccine <12 months after a nonconjugated vaccine. Of the nonresponders, 10 received a conjugated vaccine <12 months after a nonconjugated vaccine and did not mount a protective response. Other associated immunologic findings included hypogammaglobulinemia (n = 6), low immunoglobulin G1 (IgG1) levels (n = 5), and low IgG2 levels (n = 6). CONCLUSION: The majority of the patients with an inferior response to a nonconjugated vaccine also had an inferior response to a conjugated vaccine. Conjugated vaccine administration time did not affect the response rate. Analysis of the data demonstrated that patients with suspected specific antibody deficiency may not benefit from a conjugated vaccine, which suggested a defect that may affect more than pure antibody responses. Also, the majority of patients with IgG2 deficiency mounted an inadequate response to Pneumococcal 13-valent conjugate vaccine.

Adverse Effects of Nonsystemic Steroids (Inhaled, Intranasal, and Cutaneous): a Review of the Literature and Suggested Monitoring Tool.

Inhaled, intranasal, and cutaneous steroids are prescribed by physicians for a plethora of disease processes including asthma and rhinitis. While the high efficacy of this class of medication is well known, the wide range of adverse effects, both local and systemic, is not well elucidated. It is imperative to monitor total steroid burden in its varied forms as well as tracking for possible side effects that may be caused by a high cumulative dose of steroids. This review article highlights the adverse effects of different steroid modalities as well as suggests a monitoring tool to determine steroid totality and side effects.

Postchemotherapy histopathological evaluation of ovarian carcinoma: a 40-case study.

Ovarian carcinomas are conventionally treated with primary debulking surgery followed by chemotherapy. Nowadays neoadjuvant chemotherapy followed by surgery is an upcoming treatment modality for ovarian carcinoma. This study highlights the histopathological changes observed after neoadjuvant chemotherapy. Present study is a 40-case study stressing five histological parameters: residual tumour, fibrosis, necrosis, inflammation, and psammoma bodies. All these parameters carry prognostic significance and they are easily reproducible. Fleiss kappa statistics were used to measure intraobserver agreement between pathologists which was found to be substantial to almost perfect with κ ranging between 0.621 and 1.00. This study highlights easily reproducible parameters and their incorporation in histopathology report, thus helping in patient management.

Caveolin-1 deficiency exacerbates cardiac dysfunction and reduces survival in mice with myocardial infarction.

Caveolin (Cav)-1 has been involved in the pathogenesis of ischemic injuries. For instance, modulations of Cav-1 expression have been reported in animal models of myocardial infarction and cerebral ischemia-reperfusion. Furthermore, ablation of the Cav-1 gene in mice has been shown to increase the extent of ischemic injury in models of cerebral and hindlimb ischemia. Cav-1 has also been suggested to play a role in myocardial ischemic preconditioning. However, the role of Cav-1 in myocardial ischemia (MI)-induced cardiac dysfunction still remains to be determined. We determined the outcome of a permanent left anterior descending coronary artery (LAD) ligation in Cav-1 knockout (KO) mice. Wild-type (WT) and Cav-1 KO mice were subjected to permanent LAD ligation for 24 h. The progression of ischemic injury was monitored by echocardiography, hemodynamic measurements, 2,3,5-triphenyltetrazolium chloride staining, ß-binding analysis, cAMP level measurements, and Western blot analyses. Cav-1 KO mice subjected to LAD ligation display reduced survival compared with WT mice. Despite similar infarct sizes, Cav-1 KO mice subjected to MI showed reduced left ventricular (LV) ejection fraction and fractional shortening as well as increased LV end-diastolic pressures compared with their WT counterparts. Mechanistically, Cav-1 KO mice subjected to MI exhibit reduced ß-adrenergic receptor density at the plasma membrane as well as decreased cAMP levels and PKA phosphorylation. In conclusion, ablation of the Cav-1 gene exacerbates cardiac dysfunction and reduces survival in mice subjected to MI. Mechanistically, Cav-1 KO mice subjected to LAD ligation display abnormalities in ß-adrenergic signaling.