Incidental detection of rare vascular variation during pyeloplasty and its clinical implication - A case report.

ABSTRACT: Crossing vessels is one of the important causes of pelviureteric junction obstruction (PUJO). Accessory lower polar vessels are commonly seen with congenital PUJO, but they are not always the cause of obstruction. We incidentally encountered a variation in the lower polar crossing vessel while doing laparoscopic pyeloplasty in a patient with congenital PUJO. We encountered a right accessory lower polar artery and vein along with a right gonadal artery arising from the accessory right renal artery and right gonadal vein draining into the right lower polar crossing accessory renal vein. Knowledge of variations in genitourinary vasculature is important in the current era to prevent inadvertent complications.

Spotlight on 4-substituted quinolines as potential anti-infective agents: Journey beyond chloroquine.

Continued emerging resistance of pathogens against the clinically approved candidates and their associated limitations continuously demand newer agents having better potency with a more suited safety profile. Quinoline nuclei containing scaffolds of natural and synthetic origin have been documented for diverse types of pharmacological activities, and a number of drugs are clinically approved. In the present review, we unprecedentedly covered the biological potential of 4-substituted quinoline and elaborated a rationale for its special privilege to afford the significant number of approved clinical drugs, particularly against infectious pathogens. Compounds with 4-substituted quinoline are well documented for antimalarial activity, but in the last two decades, they have been extensively explored for activity against cancer, tuberculosis, and several other pathogens including viruses, bacteria, fungi, and other infectious pathogens. In the present study, the anti-infective spectrum of this scaffold is discussed against viruses, mycobacteria, malarial parasites, and fungal and bacterial strains, along with recent updates in this area, with special emphasis on the structure-activity relationship.

World Health Organization MPOWER for tobacco control in India: a 6-year retrospective analysis.

Background: Prevalence and practices of tobacco usage in India are diverse and incongruent and Government of India has enacted various laws to overcome this burden. To make tobacco control measures effective and powerful, WHO introduced MPOWER in 2004 and India was one of the first countries that implemented the MPOWER. Objective: This study is aimed to quantify the implementation of MPOWER tobacco control policies in India. Material and Methods: In this retrospective analysis, data was gathered from the WHO MPOWER of India from 2015 to 2021. This analysis was based on the checklist which was designed previously by Iranian and international tobacco control specialists in their study on tobacco control. Results: In the present comparative analysis, India was categorized by scores and these were acquired from each indicator for each activity and 2021 year got the highest scores as compared to the previous year scores i.e. 27 in 2015. In context to individual indicators, noticeable increase in scores has been seen in both health warning on cigarette packages and adult daily smoking prevalence, whereas no progress was observed in smoking related policies. Conclusion: Although MPOWER programmes are widely accepted by the Indian government, but still substantial improvement in fewer sections is required.

CT Perfusion collateral index in assessment of collaterals in acute ischemic stroke with delayed presentation: Comparison to single phase CTA.

BACKGROUND & PURPOSE: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients. METHODS: ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS. RESULTS: A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003). CONCLUSION: CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Dental professionals' attitude and willingness to respond during disaster events: a cross-sectional study.

INTRODUCTION: In the present times, natural and man-made threats have questioned our existence on this planet. Health care professionals need to be aware of all the procedures to follow during such an event that threatens to paralyze the entire community and should be able to respond effectively. OBJECTIVE: The present study was conducted to assess the willingness and attitude of dental professionals to render help during any disaster or catastrophic event. MATERIAL AND METHODS: The present cross-sectional study among 480 subjects who were residing in Tricity (Chandigarh, Mohali and Panchkula). Informed consent was taken from all the subjects. Systematic random sampling methodology was employed for selection for study sample. The study utilized a self-designed close-ended questionnaire written in English and verified by experts. The questionnaire was divided into two parts to collect the required information. The data was analyzed using SPSS software version 21; chi-square test and multiple regression analysis were used to arrive at the results. RESULTS: More than 85% of subjects had awareness regarding natural and manmade disasters. A positive response was given by 79.2% of subjects regarding willingness to help during disaster. Educational qualification of subjects was significantly associated with attitude towards some aspects of disaster response (p<0.05). Postgraduate subjects and subjects who were academicians were more willing to render help (OR: 2.18 & 3.65 respectively). CONCLUSIONS: The study emphasizes the need for educational and training programs for dentists' regarding disaster management. A short course on emergency and disaster management can be included in undergraduate and postgraduate dental curriculum.

Omicron sub-variants: is the world going to witness another wave?

Omicron, the new 'Variant of Concern' of SARS-CoV-2, is rapidly evolving into new sub-variants or sub-lineages (BA.1, BA.2 etc.). These sub-variants have higher transmissibility, decreased vaccine effectiveness and increased risk of reinfection. As a result, many nations across the globe are reporting surge in infections which is a matter of concern. Understanding Omicron and its sub-variants is vital for development of public health policy and preventing disease transmission. The present paper throws a spotlight on the newly detected sub-variants of Omicron as reported in ongoing researches which are available only in pre-print form and also the importance of a booster dose of the vaccine. Information regarding recent research on a new nasal vaccine formulation, which may be effective against the new variants, is also highlighted in the paper.

Covid-19 update: Omicron variant - a new emerging threat.

A new health threat in the form of a new variant of Covid-19 called Omicron has emerged globally in this holiday season. This new variant has been declared a variant of concern (VOC) by the World Health Organization and experts are expecting another wave of the pandemic. A lot still unknown about this variant and researchers worldwide are conducting studies to find the nature and characteristics of this mutated strain. Cases have begun to rise dramatically around the world and many countries have already imposed travel restrictions again to prevent disease transmission. It is being speculated that this particular variant has got tendency of immune escape and therefore can even infect fully vaccinated individuals. Vaccination and adhering to Covid-19 guidelines and protocols can curtail the spread of the virus. The present paper focuses on what is currently known about this variant, antigen diagnostic tests, importance of getting fully vaccinated and having booster dose etc. If we want to emerge from this pandemic, countries should practice vaccine equality and solidarity for the good of mankind.

Renal vein injury during percutaneous nephrolithotomy: A surgical catastrophe - Management and lessons learned.

Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large and complex renal calculi. We encountered a patient who was planned for PCNL in a peripheral hospital, without a preoperative computed tomography scan but was abandoned during tract dilatation due to intractable bleeding and was referred to our institute with nephrostomy in situ in a clamped state. After evaluation, the tip of the nephrostomy tube was found to be in the left renal vein causing secondary thrombosis. Due to the nonfunctional status of the kidney in the dynamic scan, the patient underwent laparoscopic left simple nephrectomy with thrombectomy without any major intraoperative complication and was discharged in stable condition.

Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study.

BACKGROUND: Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition to first-line cisplatin-gemcitabine in patients with locally advanced or metastatic biliary tract cancer. METHODS: We did a randomised, double-blind, phase 2 study at 81 hospitals across 18 countries. We enrolled patients with histologically or cytologically confirmed, non-resectable, recurrent, or metastatic biliary tract adenocarcinoma, who were treatment-naive, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, estimated life expectancy of 3 months or more, and measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1. Eligible participants were randomly assigned (2:1:2:1) to receive either intravenous ramucirumab 8 mg/kg or placebo (on days 1 and 8 in 21-day cycles) or oral merestinib 80 mg or placebo (once daily) until disease progression, unacceptable toxicity, death, or patient or investigator request for discontinuation. All participants received intravenous cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 (on days 1 and 8 in 21-day cycles), for a maximum of eight cycles. Randomisation was done by an interactive web response system using a permuted block method (blocks of six) and was stratified by primary tumour site, geographical region, and presence of metastatic disease. Participants, investigators, and the study funder were masked to treatment assignment within the intravenous and oral groups. The primary endpoint was investigator-assessed progression-free survival (in the intention-to-treat population). The safety analysis was done in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02711553, and long-term follow-up is ongoing. FINDINGS: Between May 25, 2016, and Aug 8, 2017, 450 patients were assessed for eligibility and 309 (69%) were enrolled and randomly assigned to ramucirumab (n=106), merestinib (n=102), or pooled placebo (n=101); 306 received at least one dose of study treatment. The median follow-up time for progression-free survival at data cutoff (Feb 16, 2018) was 10·9 months (IQR 8·1-14·1). Median progression-free survival was 6·5 months (80% CI 5·7-7·1) in the ramucirumab group, 7·0 months (6·2-7·1) in the merestinib group, and 6·6 months (5·6-6·8) in the pooled placebo group (ramucirumab vs placebo hazard ratio 1·12 [80% CI 0·90-1·40], two-sided stratified p=0·48; merestinib vs placebo 0·92 [0·73-1·15], two-sided stratified p=0·64). The most common grade 3 or worse adverse events were neutropenia (51 [49%] of 104 patients in the ramucirumab group; 48 [47%] of 102 in the merestinib group; and 33 [33%] of 100 in the pooled placebo group), thrombocytopenia (36 [35%]; 19 [19%]; and 17 [17%]), and anaemia (28 [27%]; 16 [16%]; and 19 [19%]). Serious adverse events occurred in 53 (51%) patients in the ramucirumab group, 56 (55%) in the merestinib group, and 48 (48%) in the pooled placebo group. Treatment-related deaths (deemed related by the investigator) occurred in one (1%) of 104 patients in the ramucirumab group (cardiac arrest) and two (2%) of 102 patients in the merestinib group (pulmonary embolism [n=1] and sepsis [n=1]). INTERPRETATION: Adding ramucirumab or merestinib to first-line cisplatin-gemcitabine was well tolerated, with no new safety signals, but neither improved progression-free survival in patients with molecularly unselected, locally advanced or metastatic biliary tract cancer. The role of these targeted inhibitors remains investigational, highlighting the need for further understanding of biliary tract malignancies and the contribution of molecular selection. FUNDING: Eli Lilly and Company.

Covid-19 and mucormycosis (Black Fungus): An epidemic within the pandemic.

The second wave of the COVID-19 pandemic has affected India significantly with country reporting more than 400,000 cases in the month of May 2021 and health system almost collapsing. This was attributed to the new mutant strain also called as the 'Delta Strain' which led to high surge of cases across the country. As the country was stabilising over this situation, another imminent threat in the form of Covid Associated Mucormycosis (CAM) challenged the already burdened health system of India. Also called as 'Black Fungus,' cases of CAM began to rise rapidly in the last week of May 2021 with multiple states reporting steady rise in the number of cases. Based on the published literature, India contributed to approximately 71% of global cases of CAM from December 2019 to start of April 2021, with majority of the cases occurring during the second wave. The present paper focuses on the epidemic of CAM during the second wave in India highlighting the causes, symptoms and various treatment modalities that have been adopted to cure the disease. Also, spotlight has also been thrown on some other nations where cases of CAM have begun to emerge. Some key recommendations are also mentioned which can prove vital towards disease prevention.

COVID-19 and fatal renal mucormycosis: Contributory or coincidental?

Association of mucormycosis with COVID-19 disease is emerging as a matter of concern, with multiple reports of rhino-cerebral-orbital and pulmonary involvement. The association of isolated renal mucormycosis in a patient with a history of COVID-19 infection is unknown. The immune dysregulation associated with COVID, along with the use of steroids, mechanical ventilation, and interleukin-6-directed therapies, predisposes to the development of mucormycosis. We report a rare case of primary renal mucormycosis in a young male following recovery from COVID-19. The unusual mode of presentation, rapidly progressive disease course, and the ensuing dilemmas in diagnosis and treatment merit critical analysis.

Comparing a thioglycosylated chlorin and phthalocyanine as potential theranostic agents.

Herein we describe the design, efficient synthesis, and photophysical properties of two macrocycle dyes for cancer theranostics. This study compares a glycosylated chlorin with a glycosylated phthalocyanine designed to specifically target cancer, wherein the photophysical properties enable both fluorescence imaging and the sensitization of the formation of reactive oxygen species (ROS) for photodynamic therapy. Both the compounds show low darktoxicity (IC50 > 100 µM). The glycosylated phthalocyanine showed low phototoxicity (IC50 > 100 µM) while glycosylated chlorin showed high phototoxicity (IC50 = 1-2 µM). ZnPcGlc8 has low solubility and also form aggregates in aqueous media, thus resulting in minimal uptake in two different human breast cancer cell lines: MDA-MB-231 and MCF-7. The glycosylated chlorin however was efficiently taken up by these two cell lines, thus allows fluorescence imaging in cells and in xenograft tumor model in mice. In this study, we find that the chlorin conjugate is the more promising theranostic agent.

Clinical and Epidemiological Features of SARS-CoV-2 Patients in SARI Ward of a Tertiary Care Centre in New Delhi.

IMPORTANCE: Rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in India. Since the first laboratory confirmed case of SARS-CoV-2 was reported from Kerala on January 30, 2020 novel coronavirus infected pneumonia (NCIP) has been presenting to the hospital emergencies as severe acute respiratory illness (SARI). We aim to find out the rate of SARS-CoV-2 positivity in SARI cases and further clarify the epidemiological and clinical characteristics of NCIP in New Delhi, India. AIMS AND OBJECTIVES: To find out the rate of SARS-CoV-2 positivity in SARI cases presenting to the hospital emergency and describe the epidemiological and clinical characteristics of NCIP. DESIGN, SETTING AND PARTICIPANTS: Retrospective, single-center case series of the 82 consecutive hospitalized patients with SARI and subsequent confirmed NCIP cases at Dr Ram Manohar Lohia Hospital, New Delhi between 10th April 2020 and 30th April 2020. MAIN OUTCOMES AND MEASURES: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. The primary composite end-point was admission to an intensive care unit (ICU), the use of mechanical ventilation or death. Patients were categorized as severe pneumonia and non-severe pneumonia at time of admission and outcome data was compared. RESULTS: Of the 82 SARI cases, 32(39%) patients were confirmed to be SARS-CoV-2 positive. The median age of NCIP cases was 54.5 years (IQR, 46.25 - 60) and 19(59.3%) of them were males. 24(75%) cases were categorized as severe pneumonia on admission. 22(68.8%) patients had 1 or more co-morbidities. Diabetes mellitus 16(50%), hypertension 11(34.4%) and chronic obstructive airway disease 5(15.6%) were the most common co-existing illnesses. Compared with the patients who did not meet the primary outcome, patients who met the primary outcome were more likely to be having at least 1 underlying comorbidity (p-0.03), diabetes (p-0.003) and hypertension (p-0.03). Common symptoms included dyspnea 29(90.6%) followed by cough 27(84.4%), fever 22(68%), bodyache and myalgias 14(43.75%). Median time from symptom onset to hospital admission was 3 days. The most common pattern on chest X-ray was bilateral patchy nodular or interstitial infiltration seen in 30(93.8%) patients. Leucopenia was present in 10(31.2%) of the patients, with majority of patients presenting with lymphocytopenia, 24(75%) [lymphocyte count (1106 cells/ dL), interquartile range {IQR}, (970-1487)]. Thrombocytopenia was seen in 14(43.8%) patients, pancytopenia in 10(31.2%) patients and anemia was seen in 14(43.8%) patients. Hypoalbuminemia was present in 22(68.8%) cases. Raised CK-MB was seen in 7(21.9%) patients. The primary composite end-point occurred in 12(37.5%) patients, including 9(28.13%) patients who required mechanical ventilation and subsequently expired. 3(9.3%) of these patients who recovered, were subsequently shifted to COVID-19 ward from the ICU. The patients who met the primary outcome were older in age (56.5 years vs 50 years), had significantly higher SOFA scores (6 vs 3.5), were in shock (41.7% vs 5%), in higher respiratory distress (66.7% vs 10%), had lower mean arterial oxygen saturation (85% vs 89.5%), had higher CK-MB values (66 vs 26)U/L [6(54.5%) vs 2(9.5%)], had hypoalbuminemia (100% vs 50%) and acute kidney injury 8(72.7%) vs 5(23.8%) on admission. Of the 50 non-COVID-19 SARI patients in our study cohort, 13 (26%) patients met the primary composite outcome. Of them 9 (18%) patients expired and remaining 4 patients have subsequently recovered. As on 17th May 2020, 23 patients were still hospitalized, recovering in COVID-19 ward. CONCLUSION AND RELEVANCE: In this single-center case series from New Delhi, out of 82 patients of SARI, 32 patients were confirmed NCIP, with a COVID-19 positivity of 39%. 75% of NCIP presented in severe pneumonia and 37.5% required ICU care. The case fatality rate was 28%.

Covid-19: a survey on knowledge, awareness and hygiene practices among dental health professionals in an Indian scenario.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) continues to spread globally. It has become a major cause of concern for health care professionals all over the world. Objective: The aim of this study was to assess knowledge, awareness and hygiene practices regarding COVID-19 among private dental practitioners practicing in Tricity (Chandigarh, Panchkula and Mohali) in India during these critical times. Materials and Methods: A total of 245 private dentists participated in this cross-sectional survey and finally 215 constituted the final sample size. A self-administered, multiple choice type questionnaire (verified by a specialist) was administered to obtain information from the subjects. The questionnaire was divided into two parts and included 15 questions on knowledge and awareness regarding COVID-19. Statistical analysis was done using ANOVA and Student's t-test. Results: Percentage of subjects who answered correctly regarding main symptoms of COVID-19 and primary mode of transmission was 87% and 82.5% respectively. One-third of the subjects were not aware regarding Personal Protective Equipment (PPE) to be used while rendering dental treatment. 75% of subjects were of the opinion that supportive care is the current treatment regime for COVID-19. Less than one-third of subjects (30.2%) reported high scores. Education level (p=0.018) and health sector profile (p=0.024) of the subjects were significantly associated with mean knowledge scores. Conclusion: The findings of the present study showed that some notable deficiencies in knowledge existed among dental professionals regarding some vital aspects of COVID-19. Therefore, there is an urgent need for improving dentists'knowledge via health education and training programs. Further studies on the subject are also warranted once the situation normalizes.

A Structural Model of Nitro-Porphyrin Dyes Based on Spectroscopy and Density Functional Theory.

Nitro-porphyrins are an important class of commercial dyes with a range of potential applications. The nitro group is known to dramatically affect the photophysics of the porphyrin, but there are few systematic investigations of the contributing factors. To address this deficiency, we present spectroscopic studies of a series of nitro-porphyrins, accompanied by density functional theory calculations to elucidate their structures. In particular, we explore how the positions of the substituents affect the energy levels and nuclear geometry. As expected, nitro groups on the meso-phenyl rings cause small changes to the orbital energies by induction, while those at the ß-pyrrole positions more strongly conjugate into the aromatic system. In addition, however, we find evidence that ß-pyrrole nitro groups distort the porphyrin, creating two non-planar conformations with distinct properties. This unexpected result helps explain the anomalous photophysics of nitro-porphyrins reported throughout the literature, including inhomogeneous line broadening and biexponential fluorescence decay. © 2017 Wiley Periodicals, Inc.

Compromising the plasma membrane as a secondary target in photodynamic therapy-induced necrosis.

Photodynamic therapy (PDT) is a non-invasive treatment widely applied to different cancers. The goal of PDT is the photo-induced destruction of cancer cells by the activation of different cell death mechanisms, including apoptosis and/or necrosis. Recent efforts focusing on understanding the mechanisms of cell death activated by PDT find that it depends on the type of photosensitizer (PS), targeted organelles, and nature of the light used. It is generally accepted that very short incubation times are required to direct the PS to the plasma membrane (PM), while longer periods result in the accumulation of the PS in internal compartments such as the endoplasmic reticulum or mitochondria. Glycosylation of the PS targets cancer via saccharide receptors on the cell surface, and is generally assumed that these compounds rapidly internalize and accumulate, e.g. in the endoplasmic reticulum. Herein we demonstrate that a minor fraction of a glycosylated chlorin compound residing at the PM of cancer cells can activate necrosis upon illumination by compromising the PM independently of the length of the incubation period. The results presented here show that the PM can also be targeted by glycosylated PS designed to accumulate in internal organelles. PS activation to induce necrosis by compromising the plasma membrane has the benefits of fast cell death and shorter irradiation times. The findings described here expand our understanding of the cellular damage induced by phototherapies, presenting the possibility of activating another cell death mechanism based on the incubation time and type of light used.

Neuroimaging in Central Nervous System Infections.

Radiologic imaging is often employed to supplement clinical evaluation in cases of suspected central nervous system (CNS) infection. While computed tomography (CT) is superior for evaluating osseous integrity, demineralization, and erosive changes and may be more readily available at many institutions, magnetic resonance imaging (MRI) has significantly greater sensitivity for evaluating the cerebral parenchyma, cord, and marrow for early changes that have not yet reached the threshold for CT detection. For these reasons, MRI is generally superior to CT for characterizing bacterial, viral, fungal, and parasitic infections of the CNS. The typical imaging features of common and uncommon CNS infectious processes are reviewed.