The predictors of outcome and progression of pediatric sepsis and septic shock: A prospective observational study from western India.

INTRODUCTION: There is a paucity of studies on the progression and outcome of Systemic Inflammatory Response Syndrome (SIRS) with its determinants. AIMS AND OBJECTIVES: To determine the predictors of the outcome and progression of pediatric sepsis and septic shock. MATERIALS AND METHODS: Prospective observational study of children fulfilling criteria of SIRS and their progression to sepsis, severe sepsis, and septic shock (clinically and biochemically) was conducted at a tertiary care center. RESULTS: Totally, 200 children were recruited over a period of 21 months (from February 2016 to October 2017). Most cases (80, 40%) were infants. Of the total, 188 (94%) cases were of an infective etiology (mostly respiratory system). Temperature and heart rate were the two commonest SIRS parameters which were deranged. Blood cultures were positive in only 25 (12.5%) cases. Out of the total 200 children, 108 progressed to sepsis, of which 26 progressed to severe sepsis, of which 22 progressed to septic shock. Abnormal leukocyte count, culture positivity and severe acute malnutrition were significantly associated with progression of SIRS patients to septic shock (P = 0.001, 0.00001 and 0.002, respectively). Factors associated with mortality were positive blood culture, multiorgan dysfunction, late hospital admissions, severe acute malnutrition, and requirement of supportive care (P values-<0.0001, <0.0001, 0.03, <0.0001 and <0.0001, respectively). CONCLUSIONS: SIRS can progress to septic shock if not identified early. The predictors of mortality were positive blood cultures, multiorgan dysfunction, late hospital admissions, severe acute malnutrition, and requirement of supportive care. The predictors of progression to septic shock were abnormal leukocyte count, culture positivity, and severe acute malnutrition.

A rare case of nephrotic syndrome: 'nailed' the diagnosis.

An 18-month-old female child presented to us with clinical features suggestive of nephrotic syndrome. Her physical examination and detailed family history highlighted the familial occurrence of abnormal nails, suggesting a diagnosis of the Nail-Patella syndrome. Nail-Patella syndrome is a rare cause of nephrotic syndrome in children. This case highlights the importance of a detailed history, including pedigree and a thorough examination of the patient.

Arterial bicarbonate may be a useful indicator of inadequate cortisol response in children with catecholamine resistant septic shock.

OBJECTIVE: To study the clinical and biochemical parameters that can predict cortisol insufficiency in children with septic shock. DESIGN: prospective, observational study. SETTING: Tertiary health-care center. PATIENTS/SUBJECTS: Fifty children admitted with the catecholamine resistant septic shock to a tertiary health-care center. MATERIALS AND METHODS: At the time of hospitalization all patients underwent detailed clinical evaluation including, history and physical examination, evaluation with the complete blood count, serum cortisol, renal function tests, liver function tests, prothrombin time activated partial thromboplastin time, arterial blood gas analysis, urine analysis, chest roentgenogram, ultrasonography of the abdomen and chest, urine, and blood culture for bacteria and fungi. RESULTS: Out of 50 children with the catecholamine resistant septic shock, seven had adrenal insufficiency (serum cortisol <18 µg/dl). Of all parameters studied, only arterial bicarbonate at the time of admission to intensive care predicted adrenal insufficiency. On Receptor operative characteristic curve analysis, a bicarbonate level of 10.9 mEq/L had the best accuracy to predict adrenal insufficiency. CONCLUSION: Arterial bicarbonate may be used as a rapid test for provisional identification of adrenal insufficiency among children with the catecholamine resistant septic shock.

Dental management of a child with Wiskott Aldrich syndrome prior to bone marrow transplant: A case report.

AIM: Orodental manifestations are commonly presented in Wiskott Aldrich Syndrome (WAS). The purpose of this paper is to report a case of dental management of a 5-year-old male child with WAS before Hematopoietic Stem Cell Transplantation (HSCT). Such patients are more prone to infection due to pretransplantation chemotherapy and posttransplantation immunosuppression; thus, it becomes imperative to eliminate all potential sources of infection before transplantation. MATERIALS AND METHODS: Fluctuating blood parameters before the dental procedure was an important challenge in rendering dental treatment. Dental procedures were carried out under general anesthesia by maintaining the hematological parameters with blood and platelet transfusion. The conventional dental treatment may not be applicable in such patients as failure of dental treatment can cause the failure of HSCT, and it has to be modified based on the clinical acumen and recommendations. CONCLUSIONS: This case report focuses on the measures to be taken before, during, and after the dental procedure to ensure the success of the dental therapy and prevent failure of HSCT due to residual dental foci of infection. A multidisciplinary approach involving a pedodontist, a pediatrician, and a hematologist can improve the quality of life of such patients.

Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate.

BACKGROUND: Imatinib mesylate has shown promising results in chronic myeloid leukemia (CML) in all phases. This drug is an effective treatment for patients with CML in chronic phase as it induces hematological remission in nearly all patients and cytogenetic responses in many. The bone marrow changes produced by this drug are different from the treatment modalities used earlier in CML. MATERIALS & METHODS: We studied 80 patients of CML on treatment with Imatinib at doses of 400-800 mg per day. Morphological and cytogenetic evaluation (Ph analysis) of bone marrow aspirates was done at six months of treatment. RESULT: In our study, 95% (76 out of 80) patients showed complete hematological response and 63.3% showed major cytogenetic response at the end of six months of treatment. The most commonly observed changes in the bone marrow aspirates at the end of six months of therapy were in the form of reduction in the cellularity, reduction in the M: E ratio to a mean of 2:1, presence of relative erythroid hyperplasia, normalization of megakaryocytic morphology and variable increase in the bone marrow lymphocytes. None of these changes had significant correlation with the patient's Ph status. CONCLUSION: We advise study of trephine biopsies to overcome the often-faced problem of hemodiluted aspirates in these cases and evaluation of sequential bone marrows to check the durability of these morphological changes and their correlation with the cytogenetic response with emphasis on cytogenetic changes other than Ph positivity.

Liquid biopsy: A potential and promising diagnostic tool for advanced stage non-small cell lung cancer patients.

More than 50% of non-small cell lung cancer (NSCLC) cases harbor an actionable mutation, and molecular testing at different intervals can help in personalized and targeted treatment. Core tissue biopsy and needle biopsy done at the time of diagnosis/disease progression are interventional, time-consuming and can affect the patients adversely. Noninterventional biomarker testing by liquid biopsy promises to revolutionize advanced stage cancer screening. The present report was formulated based on an expert panel meeting of renowned oncologists who gave their opinions for minimally invasive liquid biopsy to detect targetable molecular biomarkers in advanced NSCLC cases. An exhaustive literature search was done to support their recommendations. Clinical utility of minimally invasive liquid biopsy, for detection of molecular biomarkers in advanced stage NSCLC patients, was broadly discussed by the key opinion leaders.

Entanglement between more than two hundred macroscopic atomic ensembles in a solid.

There are both fundamental and practical motivations for studying whether quantum entanglement can exist in macroscopic systems. However, multiparty entanglement is generally fragile and difficult to quantify. Dicke states are multiparty entangled states where a single excitation is delocalized over many systems. Building on previous work on quantum memories for photons, we create a Dicke state in a solid by storing a single photon in a crystal that contains many large atomic ensembles with distinct resonance frequencies. The photon is re-emitted at a well-defined time due to an interference effect analogous to multi-slit diffraction. We derive a lower bound for the number of entangled ensembles based on the contrast of the interference and the single-photon character of the input, and we experimentally demonstrate entanglement between over two hundred ensembles, each containing a billion atoms. We also illustrate the fact that each individual ensemble contains further entanglement.Multipartite entanglement is of both fundamental and practical interest, but is notoriously difficult to witness and characterise. Here, Zarkeshian et al. demonstrate multipartite entanglement in an atomic frequency comb storing a single photon in a Dicke state spread over a macroscopic ensemble.

Successful complete regression of isolated intramedullary spinal cord metastases from epithelial ovarian carcinoma with chemotherapy and radiotherapy.

Advances in the management of ovarian cancer by use of aggressive surgery and effective platinum-based chemotherapy have prolonged survival; this may have resulted in an alteration of the metastatic pattern of the disease and spread to unusual sites (e.g, CNS) has become more common. Also, with the availability of more sensitive imaging techniques, these tumors are being diagnosed with increasing frequency. Intramedullary spinal cord metastasis is rare. We report one such case treated successfully with chemotherapy and radiotherapy with long-term survival.

Insulin resistance and beta cell function in chronically transfused patients of thalassemia major.

OBJECTIVE: To assess the glycometabolic function in chronically transfused patients of beta- thalassemia major in terms of glucose tolerance, insulin secretion, insulin resistance index, and beta cell function index and to determine their relationship with clinical and biochemical profile. METHODS: 30 homozygous thalassemia major children (aged 8-15 years) receiving regular blood transfusion and 10 age and sex matched normal children attending a tertiary level hospital were subjected to glucose tolerance test, estimation of fasting plasma insulin level, insulin resistance index and beta cell function index. Liver enzymes, liver size and indicators of iron overload (serum ferritin, total units of blood transfused, splenic size) were recorded. RESULTS: There was no diabetes mellitus or impaired glucose tolerance test in either the cases or the controls. Fasting plasma insulin levels were significantly higher in cases than controls (P = 0.004), and correlated well with indicators of iron overload like total units of blood transfused (r = 0.41, P = 0.03), serum ferritin (r = 0.38, P = 0.038) and splenic size (r = 0.43, P = 0.03). Insulin resistance was higher in cases compared to controls (P = 0.01). It correlated well with age (r = 0.56, P = 0.006), fasting blood glucose (r = 0.8, P = 0.003), fasting plasma insulin (r = 0.95, P = 0.00001), total units of blood transfused (r = 0.52, P = 0.005), serum ferritin (r = 0.4, P = 0.02) and splenomegaly (r = 0.51, P = 0.004). Insulin resistance was higher in patients not on chelation therapy compared with those on chelation therapy (P = 0.003). The beta cell function index was higher in cases compared to the controls, but not of statistic significance (P = 0.077). It did not correlate well with total amount of blood transfused (r = -0.32, P = 0.08), serum ferritin (r = -0.138, P = 0.46), spleen size (r = 0.16, P = 0.36), or chelation therapy (P = 0.98). CONCLUSION: Diabetes mellitus or impaired glucose was not seen in chronically transfused patients of thalassemia major (between 8 and 15 years of age), in our study. Insulin resistance, compensated by hyperinsulinemia, sets in early even before the onset of frank diabetes mellitus and correlated well with age, chelation therapy and indicators of iron overload like total units of blood transfused, splenomegaly and serum ferritin.

Proposal and proof-of-principle demonstration of non-destructive detection of photonic qubits using a Tm:LiNbO3 waveguide.

Non-destructive detection of photonic qubits is an enabling technology for quantum information processing and quantum communication. For practical applications, such as quantum repeaters and networks, it is desirable to implement such detection in a way that allows some form of multiplexing as well as easy integration with other components such as solid-state quantum memories. Here, we propose an approach to non-destructive photonic qubit detection that promises to have all the mentioned features. Mediated by an impurity-doped crystal, a signal photon in an arbitrary time-bin qubit state modulates the phase of an intense probe pulse that is stored during the interaction. Using a thulium-doped waveguide in LiNbO3, we perform a proof-of-principle experiment with macroscopic signal pulses, demonstrating the expected cross-phase modulation as well as the ability to preserve the coherence between temporal modes. Our findings open the path to a new key component of quantum photonics based on rare-earth-ion-doped crystals.

Oncology Gold Standard™ practical consensus recommendations 2016 for treatment of advanced clear cell renal cell carcinoma.

The Oncology Gold Standard (OGS) Expert Group on renal cell carcinoma (RCC) developed the consensus statement to provide community oncologists practical guidelines on the management of advanced clear cell (cc) RCC using published evidence, practical experience of experts in real life management, and results of a nationwide survey involving 144 health-care professionals. Six broad question categories containing 33 unique questions cover major situations in the routine management of RCC. This document serves as a ready guide for the standard of care to optimize outcome. The table of "Take Home Messages" at the end is a convenient tool for busy practitioners.

Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non-randomized study.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the balanced reciprocal translocation t (9:22). The resulting fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. The present study evaluates 174 patients with CML treated with imatinib mesylate. Of these 174 patients, 97 were in chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients in chronic phase received imatinib mesylate in the dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the 97 patients with chronic phase, 49 patients (50.5%) achieved a major (major + complete) cytogenetic response. Of the 47 patients in accelerated phase, 10 patients (21.3%) achieved a major cytogenetic response and in 30 patients with blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis, mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation. We conclude that imatinib mesylate is a safe and effective first-line therapy for chronic myeloid leukemia.

Pseudomonas sepsis with Noma: an association?

We report here a 2.5-year-old male child with community-acquired Pseudomonal sepsis showing the characteristic lesions of ecthyma gangrenosum. The child had development of gangrenous changes of the nose and face - the 'cancrum oris' or 'Noma'. We highlight the possible association of Pseudomonas sepsis and Noma, with malnutrition playing a central role in causing both the diseases.

A comparative clinical study to assess safety and reactogenicity of a DTwP-HepB+Hib vaccine.

Hepatitis B and Haemophilus influenzae type b (Hib) infections are major public health problems in developing countries, including India. Hence, combination vaccines containing DTwP, recombinant hepatitis B and Hib conjugate vaccines have been developed. Here, we report a Phase IV study which assessed safety and reactogenicity of a new DTwP-HepB+Hib vaccine. Three doses of DTwP-HepB+Hib vaccine (Pentavac, Serum Institute of India Ltd) or Tritanrix-HB+Hib (GlaxoSmithKline Beecham) were administered to infants at 6, 10 and 14 weeks of age in 2:1 ratio. The subjects were followed till one month after the third dose for safety assessment. Adverse events were captured in structured diaries and physical examinations were performed on each visit. The study was conducted in 1510 infants. Both vaccines caused injection site local and systemic reactions and the incidence was similar in both the groups. The incidence of local solicited reactions was: tenderness 35.9 %-33.6 %; redness 18.1 %-17.2 %; swelling 23.7 %-22.4 %; induration 12.8 % -13.7 %. The percentage of systemic solicited reactions were: diarrhea 2.2 %-2.2 %; drowsiness 3.3 %-3.4 %; fever 14.0 %-11.2 %; irritability 28.1 %-25.4 %; loss of appetite 6.6 %-5.6 %; persistent crying 17.7 %-15.7 %; vomiting 3.5 %-3.0 %. No serious adverse event was caused by the vaccines. The new DTwP-HepB+Hib combination vaccine showed similar safety profile to that of an imported vaccine in Indian infants.

Primary non-Hodgkin's lymphoma of the bone: a single institution experience.

UNLABELLED: Primary non-Hodgkin's lymphoma of the bone is an unusual entity. Twenty-five patients with diffuse large cell lymphoma of the bone were registered at the Tata Memorial Hospital (TMH) from August, 1991, to May, 2002. Pain at the local site and soft tissue swelling were the commonest symptoms. Involvement of the bones in the lower half of the body was more frequent than the bones in the upper half. Osteolytic lesions and an associated soft tissue mass were the common radiological findings. Nineteen patients received CHOP chemotherapy and five received COP chemotherapy. Twenty-three patients received involved field radiotherapy. The overall response to therapy was 96%. On follow-up, two patients had a nodal relapse. One patient died of progressive disease, and one patient died of cryptococcal meningitis. There were no deaths due to treatment-related toxicity. The mean progression free survival was 9.39 yr and the overall survival was 11.66 yr. The median overall survival has not been reached. At last follow-up, 21 patients were being following up at TMH and are free of disease. CONCLUSION: Primary bone lymphoma is a malignancy that is highly curable with a combination of chemotherapy and radiotherapy.

Neoadjuvant chemotherapy with ifosfamide and cisplatin combination in advanced head and neck cancer: a retrospective analysis of 519 patients: a single institution experience.

Advanced head and neck cancer is a major therapeutic problem in India. Ifosfamide has shown significant activity as a single agent in head and neck squamous carcinoma. In this study, we present our experience with two cycles of ifosfamide and cisplatin in the neoadjuvant setting given to a total of 519 patients. The complete response rate was 20% and the overall response rate was 80%. The treatment was well tolerated, there was no need for dose reduction, and there were no life-threatening side effects. We feel that this high response rate is sufficient to warrant more studies using ifosfamide-based combinations in a neoadjuvant setting for squamous carcinoma of the head and neck.

Two- vs three-drug combination chemotherapy in advanced or recurrent head and neck cancer: a single institution experience of 361 patients.

Head and neck squamous cancer is a major concern in India. The proportion of advanced cases is significantly high, and these patients have dismal survival prospects despite aggressive therapy. Often surgical resection and/or radiotherapy are not feasible in these patients. Hence, we decided to explore the option of neoadjuvant chemotherapy using effective agents like ifosfamide and paclitaxel in combination with cisplatin in these patients. A total of 361 patients were evaluable at the end of study. Of these, 207 had received ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel) in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration of response was 5.5 mo; whereas the group in which taxanes were added, showed an overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of response of 10 mo. The toxicity in both the groups was acceptable and there was no mortality. We conclude that taxane-based combinations have a significant activity in advanced head and neck squamous cancer and warrant further studies.

Infantile mediastinal primary endodermal sinus tumour.

Primary extragonadal mediastinal endodermal sinus tumour is rare, and to date very few cases have been reported in the literature. We present here a case of rare extragonadal highly malignant commonest germ cell tumour in an infant who presented with a rapidly progressive mediastinal mass with dry non-productive cough, tachypnea without significant respiratory distress or toxicity.

Colloid cyst of the third ventricle: a cause of sudden death in a child.

Colloid cyst is a rare benign intracranial neoplasm, commonly located in the third ventricle. Though headache and visual symptoms are classical, the patients may present with sudden neurological deterioration. We present a ten-year-old male child who presented with sudden neurological deterioration due to colloid cyst of the third ventricle resulting in death. The child had intermittent headache for three months, for which medical attention was not sought. This report details the case and a short review of the condition is presented (with emphasis on the clinical features and importance of early diagnosis). Management (including surgical methods and conservative treatment) of third ventricle colloid cysts is briefly reviewed.

Familial glucocorticoid deficiency, alacrimia and achalasia--Allgrove syndrome.

We report three brothers with Allgrove syndrome. All three had evidence of adrenal insufficiency and deficient tear production, though neither of them had achalasia, the third component of the disorder at the time of this report. Neurological abnormalities were present in the index case. The younger siblings were neurologically normal. The familial association of achalasia, alacrimia and adrenal insufficiency, rather than being fortuitous, is a distinct clinical entity.