Tenofovir-induced distal renal tubular acidosis: A rare cause of recurrent hypokalaemic paralysis.

Tenofovir disoproxil fumarate was the first nucleotide analogue reverse transcriptase inhibitor to be approved for treatment of human immunodeficiency virus infection. It is a relatively safe drug but can present with nephrotoxicity. We report a case of 36-year-old male who presented with acute onset flaccid paraparesis. He was a diagnosed case of acquired immunodeficiency syndrome for 9 years ago and was on tenofovir-based antiretroviral therapy for last 6 months. As the patient had normal anion gap metabolic acidosis, hypokalaemia and urine pH > 5.5, distal renal tubular acidosis (RTA) was suspected. He improved dramatically within 24 h of hospitalisation after potassium correction to regain normal power. Tenofovir-induced distal RTA presenting as hypokalaemic paralysis is a very rare complication of tenofovir; hence, we are reporting this case. In addition, we suggest regular follow-up of patients taking tenofovir with urine analysis and serum potassium to detect this complication earlier as it is reversible.

Lung Findings in Minimally Invasive Tissue Sampling (MITS) Examinations of Fetal and Preterm Neonatal Deaths: A Report From the PURPOSe Study.

BACKGROUND: Complete diagnostic autopsy (CDA) is considered to be the gold-standard procedure that aids in determination of cause of death in stillbirths and neonatal deaths. However, CDA is not routinely practiced in South Asian countries due to religious beliefs, lack of expertise, and lack of resources. Minimally invasive tissue sampling (MITS) has been recommended as a less mutilating and less expensive alternative to CDA for obtaining tissues for analysis. The present study aims to evaluate the yield of lung tissue and histological findings using MITS as part of a cause of death analysis for stillborns and preterm neonatal deaths. METHODS: Data were collected during an observational multicenter prospective study called the Project to Understand and Research Preterm birth and Stillbirth (PURPOSe) conducted in India and Pakistan. After obtaining written informed consent from parents, the eligible stillbirths and neonatal deaths were subjected to MITS using a standard protocol. The tissues were obtained from both lungs for histological and microbiological analysis. RESULTS: At both sites, a total of 453 stillbirths and 352 neonatal deaths underwent MITS. For stillbirths and neonatal deaths, the yield of lung tissue using MITS was high (92%). Intrauterine fetal distress and respiratory distress syndrome were the leading lung pathologies reported in stillbirths and neonatal deaths, respectively. CONCLUSIONS: MITS appears to be a reasonable alternative to CDA in obtaining and evaluating lung tissue to inform accurate cause of death analysis in stillbirth and preterm deaths.

Maternal and fetal vascular lesions of malperfusion in the placentas associated with fetal and neonatal death: results of a prospective observational study.

BACKGROUND: Fetal death is one of the major adverse pregnancy outcomes and is common in low- and middle-income countries. Placental lesions may play an important role in the etiology of fetal and neonatal deaths. Previous research relating placental lesions to fetal death causation was hindered by a lack of agreement on a placental classification scheme. The Amsterdam consensus statement that was published in 2016 focused its attention on malperfusions in the maternal and fetal placental circulations. OBJECTIVE: This study aimed to investigate the relationships of placental maternal and fetal vascular malperfusions in fetal and neonatal deaths, focusing on the most important maternal clinical conditions in the pathway to fetal and neonatal deaths, such as maternal hypertension, antepartum hemorrhage, and decreased fetal growth. STUDY DESIGN: This was a prospective, observational cohort study conducted at 2 Asian sites. The data collected included clinical history, gross and histologic evaluations of the placenta, and several other investigations and were used to determine the cause of death. The placenta was evaluated at both sites using the Amsterdam consensus framework. We estimated the risk of placental maternal and fetal vascular malperfusions in fetal and neonatal deaths. RESULTS: Between July 2018 and January 2020 in India and Pakistan, 1633 women with placentas available for the study provided consent. Of these women, 814 had fetal deaths, 618 had preterm live births and subsequent neonatal deaths, and 201 had term live births. The prevalence of maternal vascular malperfusion was higher in the placentas associated with fetal deaths (58.4%) and preterm neonatal deaths (31.1%) than in the placentas associated with term live births (15.4%). Adjusting for site, maternal vascular malperfusion had a relative risk of 3.88 (95% confidence interval, 2.70-5.59) in fetal deaths vs term live births and a relative risk of 2.07 (95% confidence interval, 1.41-3.02) in preterm neonatal deaths vs term live births. Infarcts and distal villous hypoplasia were the most common histologic components of maternal vascular malperfusion. Compared with maternal vascular malperfusion (58.4%), fetal vascular malperfusion was less common in the placentas associated with fetal deaths (19.0%). However, there were higher frequencies of fetal vascular malperfusion in the placentas associated with fetal deaths (19.0%) than in placentas associated with neonatal deaths (8.3%) or term live birth (5.0%). Adjusting for site, fetal vascular malperfusion had a relative risk of 4.09 (95% confidence interval, 2.15-7.75) in fetal deaths vs term live births and a relative risk of 1.77 (95% confidence interval, 0.90-3.49) in preterm neonatal deaths vs term live births. Furthermore, there was a higher incidence of maternal vascular malperfusion in cases of maternal hypertension (71.4%), small for gestational age (69.9%), and antepartum hemorrhage (59.1%) than in cases of fetal deaths with none of these conditions (43.3%). There was no significant difference in the occurrence of fetal vascular malperfusion in the 4 clinical categories. CONCLUSION: Histologic examination of the placenta, especially for malperfusion disorders, is crucial in elucidating pathways to fetal and neonatal deaths in preterm infants. In particular, focusing on placental maternal and fetal vascular malperfusions during pregnancy is a means to identify fetuses at risk of fetal death and is an important strategy to reduce the risk of fetal death early delivery. We hope that the increased risk of fetal and neonatal deaths in these pregnancies can be reduced by the development of an intervention that reduces the likelihood of developing maternal and fetal vascular malperfusion.

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification.

Objectives. Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor, characterized by inactivation of INI1/hSNF5 gene and loss of its protein. We studied the histomorphological and immunohistochemical spectrum of this tumor including cyclin D1 expression and MYC gene amplification. Methods. Cases with INI1 loss by immunohistochemistry (IHC; from 2005 to 2018) were retrieved, reviewed, and evaluated for cyclin D1 expression by additional IHC and fluorescence in situ hybridization for MYC genes. Results. A total of 66 cases were identified. Age ranged from 1 to 20 years (≤3 years, 44 cases; >3 years, 22). Male to female ratio was 1.7:1. Tumor locations were as follows: posterior fossa: 30; supratentorial: 31; spinal: 5. AT/RT in patient ≤3 years was frequently located in the posterior fossa, composed of primitive embryonal morphology (P = .02), rarely had ample rhabdoid cells (P = .05), and had a negative impact on overall survival (P = .04). The rhabdoid cells was a conspicuous component of posterior fossa tumors compared with the supratentorial ones (P = .06). The supratentorial tumors (P = .06), absence of rhabdoid cells (P = .06), and the presence of immunological divergent differentiation (P = .11) had a comparatively better outcome. Cyclin D1 overexpression (n = 46) was noted in 32 cases and was frequently seen in the posterior fossa tumors (P = .02). CMYC (n = 42) amplification was seen in 1 case and the NMYC (n = 42) amplification in none. Conclusion. AT/RT can occur in the noninfantile age group, at nonconventional sites and frequently overexpress cyclin D1. The MYC alterations are almost nonexistent in AT/RT.

A Prospective Study to Compare the Efficacy of Powered Turbinectomy Versus Submucous Resection in the Surgical Management of Inferior Turbinate Hypertrophy.

Over the years many surgical techniques have been described in the literature for the treatment of inferior turbinate hypertrophy (ITH) but the debate for ideal procedure is still on. In our study we are comparing two surgical procedures namely submucosal resection (SMR) of inferior turbinate and Powered inferior turbinectomy (PT) for the management of ITH. Surgical procedures are to be analyzed in terms of results and complications by subjective and Objective assessment. A prospective study was conducted from 1st December 2011 to 1st June 2013. Subjective assessment of nasal obstruction was done by visual analogue scoring before surgery and graded into none, mild, moderate, and severe. Patients were also subjected to nasal endoscopy for objective assessment of inferior turbinate size and graded as I, II, III. A total of 60 patients were operated (30 patients in each group), patients in Group A underwent SMR and in Group B patients PT was performed. Patients were assessed for various parameters like age, gender, laterality, intra operative and postoperative complications. Overall improvement of 66.7% in Nasal Obstruction and 76.7% in size of inferior turbinate was seen in Group A, whereas improvement of 90% in nasal Obstruction and 83.3% in size of turbinate was seen in Group B. Both SMR and PT are efficient methods for relieving nasal obstruction related to ITH. However, the results in our study confirm that PT is a safe and effective procedure in relieving nasal obstruction and enabling optimal volume reduction with preservation of function of the inferior turbinate.

Preparation and evaluation of nimesulide-loaded ethylcellulose and methylcellulose nanoparticles and microparticles for oral delivery.

The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

Ante mortem diagnosis of human rabies using saliva samples: comparison of real time and conventional RT-PCR techniques.

BACKGROUND: Rabies is an enzootic and fatal disease and is still a major problem in developing countries. Ante mortem diagnosis in human cases is necessary for medical management of the patient and to ensure appropriate post-exposure treatment of contacts. Both conventional RT-PCR and Real time PCR (TaqMan) have been described for the detection of rabies virus RNA from saliva and tissue respectively, however to date, there have been no studies comparing conventional and real time PCR assays for detection of rabies virus nucleic acid using saliva samples for ante mortem diagnosis. OBJECTIVES: In this study, we evaluated the utility of conventional RT-PCR and SYBR Green I Real time PCR in the ante mortem diagnosis of rabies using saliva samples. STUDY DESIGN: Saliva samples collected from twenty-four patients presenting with typical clinical manifestations of rabies were tested in the two assays. RESULTS: Amongst the 24 samples tested, 21 samples (87.5%) were positive by either of the two molecular methods. Of these 21, rabies virus RNA was detected in 6/21 in the conventional RT-PCR assay while SYBR Green I Real time PCR could detect RNA in 18/21 samples. CONCLUSION: Real time PCR assay was more sensitive than conventional RT-PCR assay (sensitivity 75% versus 37%, p=0.0189). This study highlights the utility of molecular diagnostic tests in establishing ante mortem diagnosis of rabies using saliva samples within a few hours.