Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Gender differences in the quality of life of patients with liver cirrhosis related to hepatitis C after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, which adversely affects the quality of life (QoL) of the patient. The gender of the patient may be an important variable in the way severity of the disease is perceived. The aim of our study is to evaluate the effect of the gender variable on QoL in HCV-positive patients. METHODS: This study included a total of 52 patients (26 men and 26 women) who completed a 1-year follow-up after liver transplantation. QoL was assessed using the SF-36 questionnaire. RESULTS: Male subjects have significantly higher scores on physical role functioning, bodily pain and physical activity compared with females. Females have a better QoL compared to males with regard to the emotional state and mental health. CONCLUSIONS: These results show a significant effect of the gender variable on QoL in HCV patients.

A cross-sectional audit of informed consent of online survey: Characteristics and adherence to prevalent guidelines.

Background: Research on human participants requires formal approval from a competent ethics committee. During the recruitment of the research participants, obtaining informed consent is a prerequisite. The online survey method is used by many researchers as it can collect the data from a diverse population in a short time. Aim: This study aimed to observe the characteristics and adherence to prevalent guidelines (set by the Indian Council of Medical Research [ICMR]) of informed consent coupled with online surveys. Methods: We collected the informed consent text from online survey links obtained from a network of colleagues who got a request to participate in a survey. Data were collected from July 2020 to June 2022. The text was anonymized for further analysis. The word count, sentences, and Flesch reading ease score were calculated. The adherence to ICMR guidelines where checked by two authors individually and a consensus was reached to prepare the final result. Results: A total of 44 online surveys in English were audited and among them, 10 did not have informed consent. The informed consent in 34 surveys had a median of 6 sentences and 84 words. The median reading ease score was 45.7 (college level). The majority of the consent states the purpose of the research (91.18%), the voluntary nature of the participation (85.29%), and mentioned that it is research (64.71%). However, the rest of the components are ignored by the majority of the survey consent form. Conclusion: Informed consent form with online surveys lacks adherence to the components suggested by ICMR. Hence, the forms should be made carefully by the researchers so that the vigor of informed consent is maintained in the online surveys.

Current distribution of medical colleges in India and its potential predictors: A public domain data audit.

Background: A teaching hospital or medical college may help provide better health care delivery to the people of the vicinity. Hence, building new medical colleges and upgrading existing hospitals to teaching hospitals are being implemented in India. Objective: This study aimed to observe the current distribution of medical colleges in Indian states and find correlation with area, population, and net state domestic product (NSDP). Methods: We collected data from public domain websites provided by government agencies. The State-wise number of government and private medical colleges and their annual intake were obtained from the National Medical Commission website. The state-wise number of medical colleges, geographical area, and population were calculated as the percentage of total Indian colleges, area, and population, respectively. Spearman's correlation was calculated to find any correlation of colleges and annual intake versus parameters such as area, population, and NSDP. Results: India has a total of 612 [321 (52.45%) government-run and 291 (47.55%) private] medical colleges. Tamil Nadu (70), Uttar Pradesh (67), Karnataka (63), Maharashtra (62), and Telangana (34) are the top five states with 296 (48.37%) medical colleges. States and union territories such as Karnataka, Kerala, Maharashtra, Puducherry, Tamil Nadu, and Telangana have higher medical colleges, and states such as Assam, Bihar, Odisha, Madhya Pradesh, Rajasthan, and Uttar Pradesh have lower medical colleges when compared with their population percentages. There was significant positive correlation of number of medical colleges with area (rs = 0.769, P < 0.0001), population (rs = 0.91, P < 0.0001), and NSDP (rs = 0.91, P < 0.0001). Conclusion: The current distribution of medical colleges in India is clustered over some states. Although geographical area and population are major predictors of medical colleges in Indian states, a more population-based balanced distribution of medical colleges would help distribute quality health care to the majority of the population.

Hypoglycemic Effect of Nelumbo Nucifera Seed Extract on GLUT-4 mRNA and GLUT-4 Protein in Streptozotocin-Induced Diabetic Rats.

Background: To investigate the effect of N. nucifera hydroalcoholic seed extract on fasting blood glucose (FBG) levels, glucose transporter (GLUT)-4 mRNA, and GLUT-4 protein in the adipose tissue of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male Sprague Dawley (SD) rats were first fed with a high-fat diet (HFD) for three weeks, and then, diabetes was induced by intraperitoneal injection of STZ at a dose of 35 mg/kg bw. Rats were divided into four groups: group 1: normal rats (NC), group 2: STZ-induced diabetic rats (DC), group 3: diabetic rats with N. nucifera hydroalcoholic seed extract at a dose of 400 mg/kg bw (NN), and group 4: diabetic rats with metformin at a dose of 100 mg/kg bw (MET) for 28 days. Results: FBG level was significantly lower in the NN group than in the DC group (P < 0.05). Also, the NN group increased GLUT-4 mRNA expression and GLUT-4 protein in the adipose tissue when compared to the diabetic group. Conclusion: We conclude that the observed hypoglycemic effect of N. nucifera seed extraction in STZ-induced diabetic rats could be due to insulinomimetic activity.

Analytical Study of Mandible: Prerequisite for Sex Determination.

Background: Human skull consists of various bones. One of them is mandible which is quite resistant, tough and shows systemic differences in form between individuals of different sex. It resists putrefaction also. There are characteristic features in the mandible that help us to differentiate sex in case of unknown victims like in mass disasters or in case fragmentary remains of the skeleton are found. Analysis of mandible with regard to its features is of great assistance in the determination of sex. Materials and Methods: A total of 80 dry mandible bones were collected. Morphological and morphometric parameters were studied to determine their sex. A total of nine parameters, i.e., three non-metric and six metric parameters were observed for each mandible. Data was collected for each parameter. Results: Among 80 dry mandible bones, 55 were males and 25 were females. 81.2% males bones had a square chin whereas, 80% females had a rounded chin. Gonial flare was everted in 89% males and inverted in 68% females. Conclusion: Mandible exhibits significant sexual differences. Various morphological and morphometric parameters are essential for sex determination in case of mandible bone.

Posterior Leaflet of Mitral Valve-Is it Really Tri-scalloped? -A Morphological and Morphometric Study in North Indian Cadaveric Hearts.

Background: Maintaining normal left ventricular geometry and function depends on the mitral valve's normal integrity. Irreparable damage to the mitral valve calls for its replacement using either a valve made up of biological tissue or metal, pyrolytic carbon, and similar materials. Materials and Methods: The material consists of 50 formalin-fixed adults, seemingly normal cadaveric hearts of either sex which were received from the Department of Anatomy of various institutes in the north region. These hearts were cut open to access the mitral valve in the left ventricle. Results: In this study, the posterior leaflet was semi-oval in shape being 3.72 cm wide at the base. Usually said to be tri-scalloped, interestingly, it was found so only in 56% of the hearts; being bi-scalloped in 20% and single-cusped in 16% of the hearts. Even four scallops and six scallops were observed in three (6%) and one (2%) hearts, respectively. Conclusions: To conclude, notable variation has been seen in the scallops of posterolateral cusps in the present study. The number of scallops varies greatly as single, double, three, four, or tetra-scalloped and most significant six or hexa-scalloped which has never been reported in the previous studies. To understand the rationale behind each unique architectural layout, such noticeable variations are crucial for scientists around the world. Cardiothoracic surgeons could find this information valuable for mitral valve surgery repair.

Perceived leadership quality and empathy among Indian undergraduate medical students.

BACKGROUND: Efficient leaders from the medical fraternity may understand healthcare in depth. Empathy is important for patient care, job satisfaction, and the psychological well-being of doctors. Empathic leadership is concerned with an interest in the people around them. This study aimed to observe the perceived leadership quality and empathy among Indian medical undergraduate students, find any correlation between them, and assess age, sex, and semester of study as predictor variables for leadership and empathy. MATERIALS AND METHODS: An online cross-sectional survey was conducted on Google Forms with undergraduate medical students in India with a convenient snowball sample. The Abbreviated Self Leadership Quality (ASQL) was used to find the leadership quality and the eight-item Empathy Quotient (EQ-8) to find the empathy. Spearman's correlation coefficient was calculated between ASQL and EQ-8 score. Age, sex, and semester were used as predictor variables in regression analysis with leadership and empathy as dependent variables. RESULT: A total of 439 (50.8% male, 49.2% female) Indian undergraduate students participated in the study. Males showed higher leadership qualities. There was no gender difference in empathy. Leadership was positively correlated (rs =0.13, P = .006) with empathy in the overall sample. The age (P = .001), sex (P < .0001), and semester of study (P < .0001) successfully predicts leadership (F = 57.167, P < .0001). Although age, sex, and semester combined successfully predict empathy (F = 5.31, P = .001), individually, only a semester of study (P = .009) significantly contributes to the prediction. CONCLUSION: Male and female medical students show a similar level of empathy but male shows higher leadership quality. Leadership and empathy are positively correlated; hence, students with higher leadership quality would show higher empathy and vice versa. The age, sex, and semester of study are determinants of leadership whereas semester of study is the determinant of empathy.

Biomarkers in kidney and heart disease.

There is much symptomatic similarity between acute kidney disease and acute heart disease. Both may present with shortness of breath and chest discomfort, and thus it is not surprising that biomarkers of acute myocardial and renal disease often coexist in many physicians' diagnostic work-up schedules. In this review we explore the similarities and differences between current and future tests of myocardial and renal injury and function, with particular emphasis on the diagnostic utility of currently available biomarkers to assist with the diagnosis of cardiorenal syndromes. Imaging studies have not traditionally been viewed as clinical biomarkers, but as tests of structure and function; they contribute to the diagnostic process, and we believe that they should be considered alongside more traditional biomarkers such as blood and urine measurements of circulating proteins and metabolites. We discuss the place of natriuretic peptides, novel tests of kidney damage as well as kidney function and conclude with a discussion of their place in guiding future research studies whose goals must include better characterization of the degree of dysfunction imposed on one organ system by failure of the other.

New biomarkers for acute renal injury.

Incidence of acute kidney injury (AKI) is increasing rapidly to epidemic proportions. Development of AKI, especially in intensive care settings, is associated with increased morbidity, mortality and hospitalization costs. Currently available diagnostic tools are mostly insensitive for early diagnosis, however prompt diagnosis and risk stratification are necessary for guiding therapy and preventing progression of disease. Finding an early, reliable, suitable, easily reproducible, economical and accurate biomarker for AKI is a top research priority. In recent years, many urinary and serum proteins have been investigated as possible early markers of AKI and some of them have shown great promise. This topic reviews some of the emerging biomarkers of AKI.

Hepatitis C virus adversely affects quality of life.

BACKGROUND: Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. METHODS: Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. RESULTS: Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. CONCLUSIONS: These results show a significant impact of HCV infection on health status and subjective satisfaction.

Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative.

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.

Markers of inflammation and oxidative stress in peritoneal dialysis: a comparison between high and low peritoneal transporters.

INTRODUCTION: High transport status is reported to be associated with increased mortality in peritoneal dialysis (PD). It has been hypothesized that this might be a result of a state of chronic inflammation and increased oxidative stress. We performed this pilot study to explore this hypothesis. METHODS: Based on the standard peritoneal equilibration test, PD patients were divided in two transporter groups: LOW (Low + Low average) and HIGH (High + High Average). Markers of inflammation and oxidative stress were compared between the two groups, including C-reactive protein (CRP), plasma apoptogenic potential, monocyte HLA DR expression, Advanced Oxidative Protein Products (AOPP) and reactive carbonyl residues (RCO). RESULTS: Of 42 patients (34 male/8 female) studied, 8 patients were LOW and 34 were HIGH transporters. Median values of CRP (1.39 vs. 0.62 mg/L), plasma apoptogenic potential (15 vs. 14.5%), AOPP (118.36 vs. 113.86 micromol/L) and RCO (1.72 vs. 1.13 nmol/mg protein) were similar among LOW and HIGH transporters. However HIGH transporters had significantly lower monocyte HLA DR expression (mean fluorescent intensity (MFI) -197.89 vs. 124.98 units, p=0.02) compared with LOW transporters. CONCLUSIONS: Stable chronic PD patients with high peritoneal transport status have reduced monocyte HLA-DR expression, a biomarker of increased risk for infections. This could potentially contribute to a higher risk of mortality in this group.

Machines for continuous renal replacement therapy.

A significant number of advancements have taken place since the beginning of continuous renal replacement therapy (CRRT). In particular, high volume hemofiltration and high permeability hemofiltration have been successful extensions of the technique. The additional and combined use of sorbent has also been tested successfully. Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a friendly user interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self-loading circuit or a cartridge which includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre- or postdilution (reinfusion of substitution fluid before or after the filter) can easily be performed by changing the position of the reinfusion line. These new machines permit all CRRT methodologies to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a countercurrent dialysate at the beginning of the session. Progress has been made not only in technology in this area but also on our understanding of the pathophysiology of acute renal failure. New biomaterials and new devices are now available with new frontiers are on the horizon. We might, however, speculate that although improvements have been made, a lot remains to be done. There is no doubt that technology has progressed enormously in critical care nephrology and that more progress will come in the near future. The goal, and likely outcome, is an improvement in the morbidity and mortality of the most severely ill patients.

Early diagnosis of acute kidney injury: the promise of novel biomarkers.

The incidence of acute kidney injury (AKI) formerly referred to as acute renal failure (ARF) is increasing to epidemic proportions. Development of AKI portends excessive morbidity and mortality. AKI is associated with prolonged hospital stay, increased healthcare costs and high mortality especially in critically ill patients. The mortality rate has remained largely unchanged for many decades. Delay in the diagnosis of AKI using conventional biomarkers like urine output and serum creatinine has been one of the important obstacles in applying effective early interventions. Several new biomarkers are being evaluated in a quest for early diagnosis of AKI, among which neutrophil gelatinase-associated lipocalin (NGAL) appears to be one of the most promising. This review summarizes the recent literature on these biomarkers.

High-resolution sonography is effective in detection of soft tissue foreign bodies: experience from a rural Indian center.

OBJECTIVE: Patients with penetrating trauma or field injuries are commonly encountered by emergency physicians. Clinical examination by inspection or palpation can detect superficial foreign bodies (FBs), and radiographs can detect radiopaque FBs. However, soft tissue FBs can be easily missed. The aim of our series was to evaluate the role of high-resolution sonography in detection of soft tissue FBs. METHODS: All patients referred to our center for sonographic evaluation of suspected soft tissue FBs from 1999 to 2008 were included in this analysis. Patients were scanned with an ultrasound machine using a 7.5-MHz transducer. The suspected area was scanned in both axial and sagittal planes. The nature of the FB, length, and depth from the surface were recorded and reported. The presence of an FB was confirmed by surgical excision. RESULTS: During the study period, 123 patients underwent sonography for a suspected FB, of which 12 were lost to follow-up and excluded from the analysis. The study group included 73.8% male patients; the mean age was 36.2 years. Wood fragments and wooden thorns were the most frequently observed FBs, at 46.2% and 36.2%, respectively. The surgeon was satisfied with the reported depth of the FB from the surface in most cases (89%). The overall sensitivity and specificity of sonography were 94.5% and 53.8%. CONCLUSIONS: High-resolution sonography is a very sensitive tool in diagnosis of soft tissue FBs. It also helps the surgeon with accurate localization, permitting easy removal.

Health Related Quality of Life in Patients with Transfusion-dependent Thalassemia.

Patients with transfusion-dependent thalassemia are expected to have an unfavorable quality of life due to multiple factors. We studied the quality of life in 72 patients (age 5-39 y) with transfusion-dependent thalassemia in the era of improved care, and assessed different parameters affecting it.