Efficacy and safety of combined administration of erythropoietin and iron in comparison to iron therapy alone in orthopaedic surgery: systematic review and metanalysis / Eficacia y seguridad de la administración combinada de eritropoyetina y hierro en comparación con el tratamiento con hierro solo en cirugía ortopédica: revisión sistemática y metaanálisis

Abstract: Introduction: Iron deficiency anaemia in orthopaedic surgery is common and there is increased risk of blood transfusion and associated adverse reactions. The management involves administration of iron (oral or intravenous) and erythropoietin stimulating agents. Material and methods: We searched for PubMed, Embase, Google Scholar and Cochrane database to identify the studies from inception to April 2021. Randomized controlled trials with adult patients undergoing orthopedic surgery were included. The metanalysis compared patients who were administered combination of erythropoietin stimulating agents and iron in one group and iron alone. The primary outcome was the rate of blood transfusion and the secondary outcome studied were postoperative hemoglobin concentration, after treatment hemoglobin levels, and complications like mortality, stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism and renal dysfunction. Results: Eleven studies were included. The combination of ESA and iron decreased number of patients who required blood transfusion in comparison to patients treated with iron therapy alone (RR, 0.73; 95% CI, 0.59 to 0.91, I(2) = 65%; p = 0.005). In subgroup analysis with oral and intravenous iron, the difference was not statistically significant (p = 0.24). Administration of erythropoietin either in high (≥ 80,000 IU) or low dose (≤ 80,000 IU) resulted in lower blood transfusion rates (p = 0.0007) with no significant difference between groups. The risk of mortality, myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism did not significantly increase. Conclusion: Combined administration of ESA and iron versus iron only reduces the number of red blood cell transfusions in the postoperative period in orthopedic procedures with minimal risk of complications.

Resumen: Introducción: La anemia por deficiencia de hierro en la cirugía ortopédica es común y existe un mayor riesgo de transfusión de sangre y reacciones adversas asociadas. El tratamiento implica la administración de hierro (oral o intravenoso) y agentes estimulantes de la eritropoyetina. Material y métodos: Se realizaron búsquedas en PubMed, Embase, Google Académico y la base de datos Cochrane para identificar los estudios desde su inicio hasta Abril de 2021. Se incluyeron ensayos controlados aleatorios con pacientes adultos sometidos a cirugía ortopédica. El metaanálisis comparó pacientes a los que se les administró una combinación de agentes estimulantes de la eritropoyetina y hierro en un grupo y hierro solo. El resultado primario fue la tasa de transfusión de sangre y el resultado secundario estudiado fue la concentración de hemoglobina postoperatoria, los niveles de hemoglobina después del tratamiento y complicaciones como mortalidad, accidente cerebrovascular, infarto de miocardio, trombosis venosa profunda, embolia pulmonar y disfunción renal. Resultados: Se incluyeron 11 estudios. La combinación de AEE y hierro disminuyó el número de pacientes que requirieron transfusión de sangre en comparación con los pacientes tratados con tratamiento con hierro solo (RR, 0.73; IC del 95%, 0.59 a 0.91, I(2) = 65%; p = 0.005). En el análisis de subgrupos con hierro oral e intravenoso, la diferencia no fue estadísticamente significativa (p = 0.24). La administración de eritropoyetina en dosis altas (≥ 80,000 UI) o bajas (≤ 80,000 UI) dio lugar a tasas de transfusión de sangre más bajas (p = 0.0007) sin diferencias significativas entre los grupos. El riesgo de mortalidad, infarto de miocardio, accidente cerebrovascular, trombosis venosa profunda o embolia pulmonar no aumentó significativamente. Conclusión: La administración combinada de AEE y hierro frente al hierro solo reduce el número de transfusiones de glóbulos rojos en el período postoperatorio en procedimientos ortopédicos con un riesgo mínimo de complicaciones.

Pattern of Serious Adverse Events Associated with Administration of Different Vaccines: A US Vaccine Adverse Event Reporting System (VAERS) Database Analysis

: Different vaccine adverse event surveillance systems have been developed down the years to act as an early warning system to detect signals regarding adverse events following vaccination. Different types of serious adverse events were characterized through the analysis of US VAERS registry. Methods: The VAERS data from 2010-2019 was analysed statistically for exploration of different types of serious adverse events and the signs and symptoms associated with administration of these vaccines. Vaccines implicated in serious adverse events through VAERS were further explored for correlates in WHO Vigibase database. Results: The maximum number of patients with serious events were administered FLU3 vaccine (n=4024, 12.71%), followed by PNC13 (n=2740, 8.66%), VARZOS (n=2310, 7.30%), PPV (n=1964, 6.20%) and HIBV vaccine (n=1448, 4.57%). Of all symptoms in patients with serious adverse events, pyrexia was the major symptom in patients with life threatening illness (16.06%), hospitalization (18.83%), prolongation of hospitalization (19.64%), disability (12.05%) and mortality outcome (9.95%). Among the top three vaccines implicated in serious adverse events, analysis through WHO Vigiaccess database found general disorders and administration site conditions and skin and subcutaneous tissue disorders to be the MedDRA major system organ classes for both pnemococccal and varicella zoster vaccine. Conclusion: FLU3 (Influenza), PNC13 (pneumococcal) and VARZOS (varicella zoster) vaccines were the top three vaccines implicated in serious adverse events through VAERS database analysis though a cause and effect relationship cannot be established through the this data alone.

Pulmonary embolism with isolated right ventricular infarction.

Concomitant occurrence of pulmonary embolism and right ventricular infarction is rare. It poses important diagnostic and therapeutic implications. A case of pulmonary embolism with isolated right ventricular anterior wall infarction presented with ventricular tachycardia. One pathology could have led to the other. Two-dimensional echocardiography was useful in documenting pulmonary artery hypertension as well as regional wall motion abnormality of the right ventricle. Thrombolytic therapy and dobutamine infusion were useful. Nitrates, fluid infusion and diuretics should be used cautiously.

Efficacy of a home-made spacer with acute exacerbation of bronchial asthma: a randomized controlled trial.

Metered dose inhaler (MDI) with spacer is the preferred method for administration of aerosolized medications in pediatric asthma. The expense of commercial spacers limits their use and indigenous alternatives have therefore been developed. Information on the clinical efficacy of home-made spacers is limited. This study was conducted to compare the efficacy of a valve-less home-made spacer with a commercial spacer in delivering salbutamol via MDI in acute asthma. Asthmatic children aged 5-15 years who presented with an acute exacerbation to the pediatric chest clinic of a tertiary care hospital were enrolled in a single blinded randomized parallel group study. The study patients received 10 puffs of salbutamol (100 microg/puff) via MDI-home-made spacer or MDI-commercial spacer. Pre and post inhalation measurements of peak expiratory flow rate (PEFR), oxygen saturation (SaO2), respiratory rate (RR), pulse rate (PR) were made and compared. Sixty children were enrolled in the study, 31 were administered salbutamol via the home-made spacer and 29 via the commercial spacer. The median increase in PEFR was similar in both the groups (20.8% vs 22.2%, p=0.4), clinical improvement being satisfactory in all patients. The valve-less home-made spacer is equally efficacious and cheaper than the commercial spacer in administering bronchodilators in acute exacerbations of asthma. Further studies on the efficacy of home-made spacer in delivery of inhaled steroids are needed.

Argyrophilic nucleolar organizer regions in soft tissue tumors.

Argyrophilic nucleolar organizer region (AgNOR) staining was employed on 51 apparently normal representative soft tissues, 53 benign soft tissues tumors and 52 malignant soft tissue tumors with an aim to study the sensitivity and specificity of method in differentiating between the benign and malignant soft tissue tumors. The mean AgNORs count in apparently normal fibrous tissue was 1.02, whereas it was 0.94 in adipose tissue, 1.14 in smooth muscle tissue, 1.115 in skeletal muscle tissue, 1.025 in blood vessels endothelial lining cells and 1.04 in nerve tissue. The mean AgNOR count was found to be higher in benign soft tissue tumors as compared to respective apparently normal soft tissue and was found to be statistically significant. The mean AgNOR count in soft tissue sarcomas was found to be higher as compared to both apparently normal soft tissue and benign soft tissue tumors. An increase AgNOR score in both benign and malignant soft tissue tumors as compared to apparently normal soft tissue indicates high proliferative activity. The neurofibrosarcoma showed low AgNOR count as compared to other soft tissues sarcomas. The fibrohistiocytic sarcoma, leiomyosarcoma and angiosarcoma showed a mean AgNOR score of 4 or more than four. The mean AgNOR score was found to increase with high grade of the tumor. The AgNOR staining is simple and useful method in estimating tumor cell proliferation thereby differentiating normal soft tissue from non-neoplastic proliferative growth, benign and malignant soft tissue tumors. It may help in differentiating fibromatosis from fibrosarcoma, dermatofibrosarcoma protuberans of low grade malignancy from high grade malignant fibrous histiocytoma and benign hemangiopericytoma from malignant hemangiopericytoma.

Direct immunofluorescent studies of skin biopsies in pemphigus.

Direct immunofluorescent studies of skin biopsies from 16 pemphigus vulgaris patients revealed immunoglobulin deposits in 12 (75%) cases with fluorescence at intercellular areas in epidermis. In 2 patients (12.5%) dermoepidermal junction also showed immunoglobulin deposits. IgG was the commonest type of immunoglobulin demonstrated in 12 out of 16 (75%) cases followed by IgM in 5 (31.25%) and IgA in 1 (6.25%) cases. Seven (43.75%) cases showed presence of IgG alone while IgM with IgG was found in 4 (25%) cases. One (6.25%) case showed deposition of IgG, IgM and IgA. The results indicated that demonstration of immunoglobulin in skin biopsies by direct immunofluorescent technique is quite a useful adjunct in diagnostic confirmation of pemphigus.

Evaluation of cryostat frozen section in the diagnosis of surgical biopsies.

Cryostat frozen section technique was used on 1300 surgical biopsies. On final paraffin sections diagnosis there were 270 benign neoplasms, 200 malignant neoplasms and 830 inflammatory and non-neoplastic lesions. The overall accuracy using frozen section was 98.48 per cent with one false positive result (0.07 per cent), 17 false negative results (1.3 per cent) and 2 deferred diagnosis (0.15 per cent).

Serum immunoglobulins in leukaemia and malignant lymphoma.

The serum immunoglobulin levels were studied in 25 healthy control subjects and 23 cases of leukaemia (6 cases of acute lymphatic leukaemia, 5 cases of acute myeloid leukaemia, 2 cases of chronic lymphatic leukaemia and 10 cases of chronic myeloid leukaemia) and 17 cases of malignant lymphoma (13 cases of Hodgkin's lymphoma and 4 cases of non-Hodgkin lymphoma). The mean levels of IgG, IgA and IgM in 25 control subjects were 1573.56 +/- 91.45 mg/dl, 209.64 +/- 12.55 mg/dl and 109.81 +/- 10.03 mg/dl respectively, those in 23 cases of leukaemia were 1338.23 +/- 109.74 mg/dl, 195.53 +/- 20.72 mg/dl and 127.47 +/- 13.29 mg/dl respectively and those in 17 cases of malignant lymphoma were 996.99 +/- 99.50 mg/dl, 147.47 +/- 19.61 mg/dl and 129.35 +/- 19.95 mg/dl respectively. The mean levels of IgG and IgA were found to be decreased in cases of leukaemia with elevated levels of IgM, however, it was found to be insignificant (p less than 0.4). The mean IgG, IgA and IgM levels were found to be almost identical in different leukaemia irrespective of cytological types except in 2 cases of chronic lymphatic leukaemia which showed low levels of IgG and IgA. The mean levels of IgG and IgA were found to be significantly decreased in malignant lymphoma (p less than 0.02). IgM levels were found to be increased in 3 cases of non-Hodgkin lymphoma.

The role of imprint cytology in diagnosis of various bone and joint diseases.

Using imprint cytodiagnosis on 63 cases of bone and joint lesions, there was only one false negative result, with ten unsatisfactory smear preparations giving an overall accuracy of 82.25 per cent. Imprint cytodiagnosis is simple, cheap, rapid easy to perform and interpret because of its better cytomorphological evaluation. The accuracy rate is high when used in conjunction with various cytochemical stains.

Glycosylated haemoglobin(HbA1C) and serum protein bound hexose in diabetes mellitus.

Glycosylated haemoglobin (HbA1C) and serum protein bound hexose (SPBH) levels were estimated in 35 healthy control subjects and 35 diabetic subjects. The mean levels of SPBH in control subjects was 161.69 +/- 3.84 mg/dl. The SPBH levels in diabetic subjects were found to be increased (P less than 0.001). It was not influenced by age and sex of the patients, complications, type of diabetes and treatment received. HbA1C levels in control subjects were 5.33 +/- 0.38/dl. The HbA1C levels in diabetic subjects was found to be markedly elevated (11.95 +/- 0.46/dl) and was found to be highly significant (P less than 0.001). The levels were found to be on higher side in juvenile diabetics. A progressive linear correlation was observed between fasting blood sugar levels and concentration of SPBH and glycosylated haemoglobin concentration. A significant correlation was also observed between the levels of glycosylated haemoglobin and SPBH levels (P less than 0.05).

Xanthogranulomatous cholecystitis (XGC): a clinicopathological study of 21 cases.

Xanthogranulomatous Cholecystitis (XGC) is an uncommon inflammatory disease. In a retrospective analysis of 159 cholecystectomy specimens revealed 21 cases of diffuse and focal XGC with an overall incidence of 13.2 per cent. The age distribution was identical to those of traditional chronic cholecystitis with female predominance (M:F ratio 1:4). Gallstones were seen in 15 cases with marked thickening of the gall bladder on ultrasonography. In one case it falsely diagnosed as carcinoma on ultrasonographic examination, however, histopathologically it was turned out to be XGC. One case of XGC was associated with adenocarcinoma of gall bladder. The incidence of diffuse XGC was 5.66 per cent, whereas incidence of focal XGC was 7.54 per cent amongst chronic cholecystitis.

Extrauterine mixed mesodermal tumour of ovary with heterologous element.

The ovary is very rare site of mixed mesodermal tumour. The present case occurred in postmenopausal woman aged 52 years, in right ovary with endometrioid carcinomatous component admixed with chondrosarcomatous component and squamous element. The patient was disease free at one year follow up, with no evidence of local recurrence and distant metastases and was treated post-operatively with combination therapy of radiotherapy and chemotherapy. The review of literature is discussed briefly, with its histogenesis and its differential diagnosis from immature teratoma, malignant teratoma, sertoli leydig cell tumour containing islands of cartilages and embryonal carcinoma of ovary.