Primary Ewing sarcoma of the kidney: A series of four cases.

INTRODUCTION: Ewing sarcoma (ES), the neuroectodermal derived tumour typically occurs in the bone and soft tissue of children and young adults. Primary ES of the kidney is strikingly rare and only a few cases and small case series have been documented. Due to the highly aggressive nature of this neoplasm, distinction from other morphological mimickers is truly indispensable in terms of treatment and prognosis. Here we describe the clinicopathological features of four cases of primary ES of the kidney with special emphasis on one case having extensive neural differentiation postneo- adjuvant chemotherapy (NACT). Extensive neural differentiation in renal ES has not been documented to date. CASE SERIES: Four patients (age range from 15-35 years) had kidney mass and multiple distant metastases at first presentation. Primary diagnosis of Ewing sarcoma was rendered by histopathology with the help of immunohistochemistry on core biopsy material. Tumour cells in all cases showed diffuse membranous CD99, nuclear FLI-1 and NKX2.2. Two of the patients had undergone radical nephrectomy followed by combination chemotherapy. Another two patients were first treated with neo-adjuvant chemotherapy (NACT) followed by radical nephrectomy. In one of them, histopathological examination of nephrectomy specimens revealed extensive neural differentiation. The adrenal gland was free in all four cases. The follow-up period was 12 -24 months. Three patients had survived and one of them became disease-free. CONCLUSION: Primary ES of the kidney is a rare and lethal entity. Due to overwhelming rarity, chemotherapy protocol has not been standardised and followed as ES in bone/soft tissue. Histopathological confirmation and prompt initiation of treatment may improve patient survival and outcome.

Common cloaca: An uncommon entity posing diagnostic and management challenges: Our experience with nine cases.

BACKGROUND: Cloacal anomalies are the severest and most complex of all anorectal malformations (ARMs). They require careful evaluation and meticulous surgery tailored to suit each variant. We present our experience in a series of nine cases. METHODS: This includes a retrospective review of 9 cases of cloaca managed at a tertiary care centre between 2015 and 2019. RESULTS: Associated anomalies were seen in 44% cases. The definitive surgery was performed at a mean age of 15.2 months (10 months-19 months), the definitive surgery being rectal separation with total urogenital mobilisation. The common channel as measured during panendoscopy was up to 3 cm in 7 patients (78%), and only 2 patients had a common channel of more than 3 cm (22%). Of the 34 procedures that these nine patients underwent, there were four complications (12%). The median follow-up period after stoma closure was 18 months (5-32 months), and the mean age at last follow-up was 38 months (22-48 months). Five children (63%) had spontaneous voiding and remained dry in the intervening period. Three patients (37%) had poor urinary stream with dribbling and high postvoid residue requiring clean intermittent catheterisation. Six patients had faecal soiling (66%); four had daily soiling; and two had occasional soiling. Four patients had constipation (44%). Seven patients (77%) required daily enemas for bowel evacuation and to remain dry. CONCLUSION: Cloacal anomalies are rare and complex ARMs. Satisfactory urinary and bowel continence rates can be achieved even in these complex anomalies.

Diagnostic utility of in-house loop-mediated isothermal amplification and real-time PCR targeting virB gene for direct detection of Brucella melitensis from clinical specimens.

AIMS: In this present study, the utility of a newly developed loop-mediated isothermal amplification (LAMP) and real-time PCR assays designed to amplify the virB gene region of Brucella melitensis was evaluated from human clinical specimens. METHODS AND RESULTS: Fifty-four culture-confirmed cases of brucellosis and 54 culture negative but clinically suspected cases of brucellosis were included in the study. Whole blood, serum and other nonblood specimens were collected and subjected to blood culture using automatic blood culture system, serological tests, LAMP assay and real-time PCR. Overall sensitivities of LAMP and real-time PCR assays were 67·5 and 68·3% respectively. For nonblood clinical specimens, we noticed a marked increase in the sensitivities of LAMP (88·9%) and real-time PCR (100%) assays. CONCLUSIONS: Performance of LAMP and real-time PCR was not satisfactory for whole-blood specimens because of the low abundance of bacteria or DNA. On the other hand, using nonblood specimens, both the assays showed higher sensitivity and specificity which makes them a good alternative for the rapid diagnosis of human brucellosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed LAMP and real-time PCR assays are a specific and rapid diagnostic tool for direct and early detection of Brucella in clinical specimens.

Arterio-venous malformations of uterus - diagnostic and management dilemmas.

Keeping in mind the life-threatening consequences of curettage in cases of undiagnosed uterine arterio-venous malformation (AVM), its possibility should be considered in patients presenting with abnormal heavy uterine bleeding and negative Human Chorionic Gonadotropin (ß-hCG) values. We collected a series of cases in which the patients presented with abnormal heavy uterine bleeding, some not responding to conservative treatment. In the presence of declining or low serum ß-hCG levels and ultrasound Doppler showing increased vascularity, patients were investigated to detect the possible presence of uterine AVM. In those patients in whom angiographic confirmation of uterine AVM was made, embolisation was done and the outcome was followed. In those patients in whom hysterectomy was done the histopathogy specimen was studied for the possible cause of increased vascularity. Arterio-venous shunting seen on ultrasound does not always imply a uterine AVM and some cases can present diagnostic and management dilemmas.

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

BACKGROUND: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. OBJECTIVE: To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. METHODS: Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4-6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8-10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue. RESULTS: A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function. CONCLUSION: This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition. TRIAL REGISTRATION: ISRCTN (trial number 76467492) http://isrctn.org.

Association of inflammatory cytokines, lipid peroxidation end products and nitric oxide with the clinical severity and fetal outcome in preeclampsia in Indian women.

Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.

Assessment and mitigation of radiation hazard for individuals engaged in reconnaissance survey in uranium exploration in Jharkhand, India.

The present study attempts to obtain an a priori estimate of the absorbed dose received by an individual engaged in the reconnaissance survey in Uranium exploration using a predictive mathematical regression analysis. Other radiation safety parameters such as excess lifetime cancer risk are also calculated. Study reflects that the proper handling of naturally occurring radioactive materials accounts for an absorbed dose significantly less than the prescribed limit.

Measurement of fast neutron induced (n,γ) reaction cross-section of 68Zn, 96Zr, 121Sb and 123Sb in the energy range of 1 to 2 MeV.

The (n,γ) reaction cross-section for the elements 68Zn, 96Zr, 121Sb and 123Sb, present in the reactor structural/shielding materials, was measured by neutron activation technique in the neutron energy region of 1-2 MeV as very limited data is available in this energy range. Further, the neutron spectrum peaks in this energy region for the fast breeder reactors and proposed accelerator driven sub-critical systems. The natural strontium (natSr) element was used as a neutron flux monitor by considering effective combined reaction cross-section for 86Sr(n,γ)87Srm and 87Sr(n,n')87Srm reactions. The pellets of mixture of sample and monitor were irradiated by a quasi-mono energetic fast neutron beam, generated by 7Li(p,n)7Be reaction at FOTIA, Bhabha Atomic Research Centre, Mumbai, India. The activity of activation products was measured by off-line gamma-ray spectrometry using High Purity Germanium Detector (HPGe). The present data with improved uncertainty and covariance analysis enhance the cross-section data base for better constraining the evaluated data and theoretical models. The theoretical (n,γ) reaction cross-sections were calculated using TALYS 1.96, which could reasonably explain the present data with the Fermi gas level density prescription.

Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus-positive newborns.

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.

Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection.

Comparisons of apparent mass responses of human subjects seated on rigid and elastic seats under vertical vibration.

The apparent mass (AM) responses of human body seated on elastic seat, without and with a vertical back support, are measured using a seat pressure sensing mat under three levels of vertical vibration (0.25, 0.50 and 0.75 m/s(2) rms acceleration) in 0.50-20 Hz frequency range. The responses were also measured with a rigid seat using the pressure mat and a force plate in order to examine the validity of the pressure mat. The pressure mat resulted in considerably lower AM magnitudes compared to the force plate. A correction function was proposed and applied, which resulted in comparable AM from both measurement systems for the rigid seat. The correction function was subsequently applied to derive AM of subjects seated on elastic seat. The responses revealed lower peak magnitude and corresponding frequency compared to those measured with rigid seat, irrespective of back support and excitation considered.

Comparison of Beractant Administration by Thin Catheter vs Intubation-Surfactant-Extubation (INSURE) in Preterm Infants Less than 34 Weeks Gestational Age with Respiratory Distress Syndrome - A Single Centre Experience.

BACKGROUND: Poractant administration with thin catheter is gradually gaining popularity compared to the INSURE technique. However, there is little evidence to use thin catheters for administration of beractant. With this background, we compared the effect of beractant administration with INSURE vs thin catheter in preterm infants less than 34 weeks with RDS on death/chronic lung disease (CLD). METHODS: This prospective cohort study was conducted in a tertiary NICU where inborn preterm infants≤34 weeks with RDS receiving beractant by INSURE or thin catheter were studied over two epochs- Epoch1- INSURE (Jan 2020-Oct 2020) & Epoch 2- Surfactant through thin catheter (Nov 2020-July 2021).The primary outcome was occurrence of death/CLD. Procedure related complications like transient bradycardia/desaturation, pneumothorax, failure of procedure, rates of other outcomes like failure of CPAP within 72hr, duration of invasive mechanical ventilation/ CPAP support, oxygen supplementation, other major neonatal morbidities & mortality were evaluated as secondary outcomes. RESULTS: The combined outcome of death/CLD was significantly lower in the thin catheter epoch (RR 0.56, 95% CI 0.34-0.90, p = 0.012). When analyzed independently for death/CLD, we found significantly lower number of deaths in the thin catheter epoch (RR 0.44, 95% CI 0.23-0.83, p = 0.008). Number of infants who failed CPAP within 72 hrs of life was lower in thin catheter epoch (RR 0.59, 95% CI 0.41-0.85, p = 0.003). Transient bradycardia/desaturation was higher during thin catheter technique (RR 4.17, 95% CI 2.22-7.69, p < 0.001). Incidence of severe IVH was lower with thin catheter technique (RR 0.13, 95% CI 0.02-0.98, p = 0.034). CONCLUSION: Beractant administration by thin catheter reduces combined outcome of death/CLD.

Stabilization of refraction and timing of spectacle prescription following manual small-incision cataract surgery.

Purpose: To determine the stabilization of refraction at 2 weeks following MSICS by comparing the difference in spherical, cylindrical component and also spherical equivalent of refraction of 2 weeks follow-up with that of 6 weeks following surgery. Methods: The difference of spherical, cylindrical component and also spherical equivalent of refraction at 2 weeks and 6 weeks follow-up of 194 eyes that underwent uncomplicated MSICS with implantation of PMMA IOL conducted by a single experienced surgeon were compared to find out the amount of change and its significance was statistically tested by Wilcoxon-Signed Rank Test. Results: The difference in spherical power (0.04 ± 0.30), cylinder power (0.03 ± 0.40), and spherical equivalent (0.06 ± 0.34) were very small and not significant statistically (P-value ≤0.05). Conclusion: Necessary spectacle correction can safely be prescribed after 2 weeks following MSICS as subjective refraction stabilizes by that time without undergoing significant change. However, our observation was applicable in patients who had an uneventful cataract surgery without any risk factor, which can delay wound healing or cause poor visual outcome.

Evaluation of pain and physiological stress during targeted neonatal echocardiography.

BACKGROUND: Targeted neonatal echocardiography (Tn-Echo) is a non-invasive examination which may cause pain/discomfort and physiological instability in neonates, but there is little evidence for the same. We conducted this study to evaluate whether targeted neonatal echocardiography causes pain or physiological stress to newborn infants. METHODS: This cross-sectional study was conducted in a tertiary level NICU. Neonates undergoing targeted neonatal echocardiography were enrolled in this study. Pain was assessed using Premature Infant Pain Profile-Revised (PIPP-R) score before, during and after targeted neonatal echocardiography examination. Heart rate, oxygen saturation, perfusion index and blood pressure were also recorded at the same time points. RESULTS: A total of 88 neonates were enrolled. Mean (SD) PIPP-R score during Tn-Echo was 8.18 (2.6) versus 3.60 (1.8) and 4.24 (2.0) before and after respectively (p value < 0.001). Heart rate and respiratory rate were significantly higher during targeted neonatal echocardiography; oxygen saturation and perfusion index were significantly lower during targeted neonatal echocardiography. Preterm infants had higher PIPP-R score compared to term neonates before, during and after the Tn-Echo [8.76 (2.4) versus 6.81 (2.4); p value < 0.001]. CONCLUSION: Targeted neonatal echocardiography causes significant pain/discomfort and physiological instability in neonates.

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

AIM: To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). METHODS: Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 µg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 µm. RESULTS: Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 µm (±75). CONCLUSION: This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.