Prospective Phase II Study of Radiotherapy Dose Escalation in Grade 4 Glioma Using 68Ga-Pentixafor PET Scan.

AIMS: Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68Ga-Pentixafor PET scan. High 68Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain. MATERIALS AND METHODS: This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range. RESULTS: Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis. CONCLUSIONS: The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of 68Ga-pentixafor PET scan for radiation dose escalation should be further explored. CLINICAL TRIAL NUMBER: CTRI/2019/05/019146.

Comparative Comprehensive Analysis on Natural Infections of Hymenolepis Diminuta and Hymenolepis Nana in Commensal Rodents.

This first comprehensive report from Punjab province of India relates to patho-physiological alterations alongwith morpho-molecular characterisation and risk assessment of natural infections of Hymenolepis diminuta and Hymenolepis nana in 291commensal rodents including house rat, Rattus rattus (n=201) and lesser bandicoot rat, Bandicota bangalensis (n=90). Small intestine of 53.61 and 64.95 % rats was found infected with H. diminuta and H. nana, respectively with a concurrent infection rate of 50.86 %. There was no association between male and female rats and H. diminuta and H. nana infections (ᵡ2 = 0.016 and 0.08, respectively, d.f.= 1, P>0.05), while the host age had significant effect on prevalence of H. diminuta and H. nana (ᵡ2 = 28.12 and 7.18, respectively, d.f.= 1, P≤0.05) infection. Examination of faecal samples and intestinal contents revealed globular shaped eggs of H. diminuta without polar filaments (76.50 ± 3.01µm x 67.62 ± 2.42 µm), while smaller sized oval eggs of H. nana were with 4 - 8 polar filaments (47.87 ± 1.95 µm x 36.12 ± 3.05 µm). Cestode infection caused enteritis, sloughing of intestinal mucosa, necrosis of villi and inflammatory reaction with infiltration of mononuclear cells in the mucosa and submucosa. Morphometric identification of the adult cestodes recovered from the intestinal lumen was confirmed by molecular characterisation based on nuclear ITS-2 loci which showed a single band of 269 bp and 242 bp for H. diminuta and H. nana, respectively. Pairwise alignment of the ITS-2 regions showed 99.46 % similarity with sequences of H. diminuta from USA and 100 % similarity with sequences of H. nana from Slovakia, Kosice.

Comparative analysis of Truenat™ MTB Plus and Xpert® Ultra in diagnosing tuberculous meningitis.

BACKGROUND: Diagnostic delay and drug resistance not only worsen the outcomes of tuberculous meningitis (TBM), but are also important impediments to TB elimination efforts. Given the need for a near point-of-care test suitable for primary healthcare centres and simultaneous detection of resistance, Truenat™ MTB Plus assay was evaluated on a large cohort of TBM patients.METHODS: Truenat assay was performed on 148 cerebrospinal fluid specimens (76 definite TBM, 32 probable TBM and 40 non-TBM controls) and its performance was compared with Xpert® Ultra.RESULTS: The overall sensitivity of Truenat and Ultra was respectively 78.7% and 67.6% in diagnosing TBM, and respectively 85.5% and 96% in diagnosing definite TBM. Twenty-three additional cases were detected using Truenat and 11 using Ultra. Truenat missed seven cases of rifampicin (RIF) resistance and indicated false RIF resistance in four cases.CONCLUSION: Performance of Truenat was comparable to that of Ultra in diagnosing TBM and inferior to Xpert Ultra in determining RIF resistance.

Molecular characterization and histo-physiological alterations induced by concurrent helminthosis in the liver of urban commensal rodents in Punjab, India.

BACKGROUND: Rodents harbour a number of parasites of public health importance, thus, they threaten human health and livestock. AIMS: The present study aimed to characterize two helminthic species found in commensal rodents and record histo-physiological alterations induced by them. METHODS: A total of 300 synanthropic rodents of three species: Rattus rattus (n=201), Bandicota bengalensis (n=90), and Mus musculus ( n=09 ) were live trapped and necropsied in different seasons during November 2017 to October 2019 at Ludhiana, Punjab, India. RESULTS: Liver of two species B. bengalensis (72.22%) and R. rattus (65.67%) were found infected with two helminthic parasites Taenia taeniaeformis, and Calodium hepaticum. These endoparasites were present either alone (4.33-6.33%) or as mixed infection (65.55%). The level of total proteins and liver marker enzymes including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were found significantly higher in the liver of rodent species infected with single and mixed infection compared to those with no infection. In histopathological assay, granulomatous liver lesions and necrosis of hepatocytes were seen which were associated with eggs and adults of C. hepaticum and inflammatory reaction in hepatic parenchyma adjoining to cysts of T. taeniaeformis. Based upon scanning electron microscopy (SEM) identification and molecular characterization using mitochondrial cytochrome oxidase I (COI) region, the metacestodes in whitish cysts were confirmed to be of T. taeniaeformis for the first time in Punjab, India. CONCLUSION: The study highlights an alarmingly high infection of rodents with zoonotic parasites and suggests immediate pest (rodent) control to check the dissemination of zoonotic diseases by helminth species under study.

Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.

BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

Prosthetic Management of Microstomia with Customized Dynamic Splint.

Microstomia is a clinical condition of reduced mouth opening that can be acquired or congenital in origin. Problems associated with microstomia can be related to function, esthetics, or both. Management of microstomia due to facial burns is complex due to the presence of hypertrophic and contracture scars. Available treatment options can be broadly classified as surgical, nonsurgical, or both. Splints can be used to prevent the contraction of perioral musculature or to recuperate lost mouth opening. Various intraoral or extraoral, tooth-borne or tissue-borne, and static or dynamic appliances are in clinical use, but their designs are case specific. This case report explains the management of microstomia secondary to facial burns by using a dynamic splint in combination with intralesional injections of triamcinolone acetonide and hyaluronidase.

Correction to: HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study.

In Abstract, under the section "Results", the first and third p values are incorrect. The correct p values should be p = 0.0004 and p < 0.0001 respectively.

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study.

PURPOSE: Currently available local anesthetics have not demonstrated sufficient analgesia beyond 12-24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl). METHODS: A phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure. RESULTS: The study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity. CONCLUSIONS: HTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.

Prevalence of allergic bronchopulmonary aspergillosis among patients with severe bronchial asthma in a tertiary care hospital in Northern India.

INTRODUCTION: The link between fungi and asthma has been known for centuries. About one-third to one-half of severe asthmatics has history of atopic sensitization to filamentous fungi, most predominantly to Aspergillus fumigatus. Allergic bronchopulmonary aspergillosis (ABPA) is the one of the most documented fungal presentations among patients with asthma. This study was done on 50 patients with severe asthma who were consecutively enrolled from January 2016 to June 2017 to look for prevalence of ABPA. MATERIALS AND METHODS: Blood samples were collected from 50 patients with severe asthma, and serum was separated to test for absolute eosinophil count, total IgE, and Aspergillus fumigates-specific IgE. RESULTS: The prevalence of ABPA was found to be 70% (35/50). Of these, ABPA-B (ABPA with bronchiectasis) was less 31.4% (11/35) when compared with 68.5% (24/35) of patients with serological ABPA. Out of these 35 patients, there were 18 females and 17 were males. The mean age of the patients was 41.3 years. CONCLUSION: ABPA prevalence is high in patients with severe asthma, and there is a need to look for and evaluate this association further.

Clinical outcome and predictors of severity in scrub typhus patients at a tertiary care hospital in Chandigarh, India.

BACKGROUND & OBJECTIVES: Scrub typhus is an under-reported rickettsial illness caused by Orientia tsutsugamushi which is transmitted by trombiculid mites. Serious complications are not uncommon and multiorgan dysfunction may develop leading to death. Paucity of data on the clinical spectrum and determinants of aftermath may be contributing to higher mortality in the region. A prospective study was done to describe the spectrum of organ dysfunction in serologically confirmed cases of scrub typhus and document predictors of adverse outcomes. METHODS: This prospective study was carried out in patients diagnosed to have scrub typhus by IgM ELISA. The clinical features, investigations and complications among survivors were statistically compared to those in the deceased. Fisher's exact test, t-test and logistic regression have been applied where appropriate. RESULTS: The study population comprised of 123 patients. Majority of patients (62%) had one or more organ dysfunction. Ten patients (8.1%) did not survive. Complications documented were acute kidney injury (AKI) in 35%, hepatitis in 29.2%, acute respiratory distress syndrome (ARDS) in 26%, shock in 13%, meningitis in 5.7%, disseminated intravascular coagulation (DIC) in 2.6%, pancreatitis in 2.6% and myocarditis in 1.6%. Certain clinical features, biochemical parameters and complications had statistically significant correlation with the outcome. The mean SOFA score was considerably higher in those who did not survive. Interpretation &conclusion: Patients developing hepatic dysfunction, acute kidney injury and respiratory distress should be identified early and intensively monitored. The SOFA score can be utilized to assess the severity at admission and rapidly triage the sicker patients.

Formalin disinfection of prostate biopsy needles may reduce post-biopsy infectious complications.

BACKGROUND: We sought to determine whether formalin disinfection of prostate biopsy needles between cores reduces post-biopsy urinary tract infections (UTIs). METHODS: We reviewed a single-surgeon experience of transrectal prostate biopsies from 2010 to 2014. Biopsies were performed in either an operative suite, where 10% formalin was used to disinfect the needle tip between each biopsy core, or an outpatient clinic, where formalin was not used. Our primary outcome was post-biopsy UTI rates, defined as a positive urine culture within 30 days of biopsy. Infection severity was characterized by the need for admission. Patient demographics, prostate size, prior biopsies, prior UTIs, pre-biopsy antibiotics and cultures and post-biopsy cultures were analyzed. Logistic regression was used to assess predictors of post-biopsy UTIs. Statistical significance was defined as P<0.05. RESULTS: A total of 756 patients were included for analysis, including 253 who received formalin disinfection and 503 who did not. Of these, 32 patients (4.2%) experienced post-biopsy UTIs, with 8 requiring admission (all without formalin use). Infection rates were more than double in the group that did not receive formalin (5.2% vs 2.3%, P=0.085). More patients in the formalin group had undergone prior biopsies (73.9% vs 31.8%, P<0.001). On multivariable analysis, prior UTI (odds ratio (OR) 3.77, P=0.006) was a significant predictor for post-biopsy infection, whereas formalin disinfection trended towards a protective effect (OR 0.41, P=0.055). CONCLUSION: Infectious complications following prostate biopsy may be mitigated by the use of formalin disinfection of the biopsy needle between cores.

Patho-physiological observations in natural concurrent infections of helminth parasites of zoonotic importance in the wild rodents, Bandicota bengalensis.

Screening of 83 mature wild rodents of Bandicota bengalensis (52 male and 31 females), live trapped from premises near railway station, fish market and agricultural fields in Ludhiana district of Punjab province, India was carried out to assess the natural occurrence of helminth parasites and their potential as reservoirs of zoonoses. On necropsy, intestine of rats was found infected with adult cestode parasites of Hymenolepis diminuta and H. nana. Liver was found infected with Capillaria hepatica and Cysticercus fasciolaris. These parasites were present either alone or as concurrent infection. In overall, 68.67 % rats were found infected of which 59.65 % were infected with nematode parasite, C. hepatica and 75.44 % with cestode parasites. Grossly, pathognomonic lesions of C. hepatica and C. fasciolaris were seen clearly and microscopic changes were observed only in severely infected cases. Overall investigation on the effect of these parasitic infections on pathophysiology of the host revealed that rodents serve as reservoirs of these parasitic infections without having much pathogenic effect on their vital organs, fecundity and enzyme activities. Because of its close association with human habitations, B. bengalensis may act as an important source of zoonotic infections and thus direct or indirect contact with excrements and carcasses of this rodent species, should be avoided.

A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVE: To perform a systematic review and meta-analysis of the comparative studies reporting oncological and renal function outcomes of segmental ureterectomy (SU) versus radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUC). MATERIALS AND METHODS: A literature search on Pubmed, Embase, and the Cochrane library was conducted according to the PRISMA guidelines, and a meta-analysis was performed to assess cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS), intravesical recurrence free survival (IVRFS) and surgery-related variations in estimated glomerular filtration rate (eGFR). RESULTS: A total of 11 retrospective studies with 3963 patients who underwent either SU (n = 983; 24.8%) or RNU (n = 2980; 75.2%) were included. Although patients treated with SU were more likely to be diagnosed with favorable pathological features, the meta-analysis of unadjusted data revealed no significant difference between both groups in terms of CSS (HR 0.90, p = 0.33) and OS (HR 0.98, p = 0.93). Accordingly, the meta-analysis of adjusted data confirmed equivalent CSS (HR = 0.90, p = 0.47) between SU and RNU. Similarly, no significant difference was found in terms of RFS (HR 1.06, p = 0.72) and IVRFS (HR 1.35, p = 0.39). However, a significant decreased risk of impaired renal function was observed after SU when compared to RNU (mean eGFR difference = 9.32 ml/1.73 m2, p = 0.007). CONCLUSION: Although adverse patient and tumor characteristics were not equally balanced between treatment arms, our systematic review and meta-analysis supports similar oncological outcomes between SU and RNU, with better preservation of renal function after SU. As such, SU should be preferably used as the first-line treatment for low-risk ureter tumors, while considered for selected cases of high-risk disease.

Role of TLR4 C>1196T (Thr399Ile) and TLR4 A>896G (Asp299Gly) polymorphisms in a North Indian population with asthma: a case-control study.

Toll-like receptor 4 (TLR4) is the most important TLR among the pattern recognition receptors which recognizes lipopolysaccharide of gram-negative bacteria. They identify a highly conserved structure of microbes called pathogen-associated molecular patterns and activate immune and inflammatory responses that have been shown to be involved in the pathogenesis of asthma. The role of TLR4 gene polymorphisms in asthma was detected in a total of 964 individuals, including 483 healthy controls and 481 asthma patients from a North Indian population. The genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis revealed that the heterozygous genotype as well as the mutant (T) allele of the TLR4 C>1196T (Thr399Ile) polymorphism shows resistance towards asthma with OR = 0.70, 95% CI (0.49-0.99), P corrected value = 0.046 and OR = 0.72, 95% CI (0.52-0.98), P corrected value = 0.039, respectively. However, no association was found between the TLR4 A>896G (Asp299Gly) polymorphism and asthma patients (P > 0.05). This is the first study conducted in India conferring TLR4 (Thr399Ile) polymorphism resistance towards asthma, while lack of association was found between TLR4 (Asp299Gly) polymorphism and asthma in the studied North Indian population.

Current Concepts in Restoring Acquired Cranial Defects.

Restoring acquired cranial defects has been in vogue for long, and the reconstructive techniques continue to evolve. Over the decades various techniques and materials are employed in rehabilitating cranial defects. Advances in bioengineering, custom templates and Rapid prototyping technology has given greater impetus in restoring larger cranial defects. With the variety of options available it will be very crucial in deciding the best possible technique and material to rehabilitate patients with cranial defects.