Demographics and host-kill parameters of Diglyphus horticola Khan against Chromatomyia horticola (Goureau).

The pea leafminer, Chromatomyia horticola (Goureau) (Diptera: Agromyzidae) is a polyphagous and serious pest of peas. In India, this pest is attacked by many parasitoids and among them Diglyphus horticola Khan (Hymenoptera: Eulophidae) is an important one, however, demographics and pest-kill potential of this parasitoid has not been studied so far. This study presents the first report on its demographics and pest-kill potential on C. horticola. The parasitoid showed three modes of host-killing behaviour viz. host-feeding, parasitism and host-stinging. The parasitoid females killed more number of hosts by parasitism than host-feeding or host-stinging. The pre-adult survival, net reproductive rate, intrinsic rate of increase (rm) and finite rate of increase (λ) were higher on the 5-days old host larvae than those reared on the 3-days old larvae. Demographics and pest-kill parameters of D. horticola were also better on 5-days old host larvae than on 3-days old host larvae. Based on the study, D. horticola appeared to be a promising biocontrol agent for the suppression of C. horticola in peas and could be promoted through conservation biological control. Further studies are required to standardize the mass production protocol and release rates to use the parasitoid by augmentation.

Morphology of papillary muscles in the ventricles of heart - a review and meta-analysis.

OBJECTIVE: To review the morphology of papillary muscles in both the ventricles of heart. METHODS: The articles were collected from databases such as MEDLINE etc. using Google as the search engine. Keywords used were papillary muscle morphology, papillary muscle dimensions, papillary muscle blood supply, papillary muscle histology, papillary muscle development and papillary muscle biomechanical properties. Studies were included if they assessed the aforesaid features of papillary muscles. Thirty-four studies were included in the review. Meta-analysis was done for number of right and left ventricular papillary muscles and dimensions of right ventricular papillary muscles. The data obtained from these studies was synthesized, pooled and all analyses were performed using R Statistical Software (v4.1.2; R Core Team 2021) with R package meta version 5.5-0. RESULTS: Marked difference existed between papillary muscles of right and left ventricles. In right ventricle, one anterior (76%), one posterior (38%) and one septal (30%) papillary muscle were most common. In left ventricle, one anterior (46%) and two posterior papillary muscles (26%) were most common. In both the ventricles, commonly observed gross appearances of papillary muscles were conical and flat-topped. Papillary muscles were lengthier in left ventricle than right ventricle. Anterior papillary muscle was 1.36cm long, 1.36cm broad and 0.64cm thick in right ventricle. It was the largest in both right and left ventricles. CONCLUSION: The morphology and measurements of papillary muscles vary significantly. Thorough knowledge of these variations will help surgeons to determine appropriate surgical repair procedures for the valve and subvalvular apparatus.

THE CORNEAL ENDOTHELIUM IN OCULAR SURFACE DISEASE AND GLAUCOMA: MECHANISMS OF DYSFUNCTION AND TREATMENT STRATEGIES.

To determine risk factors and the overall incidence of ocular surface disorders in a cohort of long-term glaucoma patients. Utilizing simple clinical tools, cross-sectional observational research were constructed to evaluate ocular surface problems and indicators. Using a four-grade scale, ten queries regarding symptoms and indications on the cornea's surface were used to create an OSD severity score. The patients were divided into three groups: A, B, and C, depending on the result. The variables that increase the incidence of surface sickness were identified using a multinomial logistic regression. Five hundred and twenty patients made up the total population. According to the multivariate analysis, the patient's age, the number of daily eyedrops, any previous changes in topical treatment for ocular intolerance, intraocular pressure, and degree of glaucoma were all connected with the severity of ocular surface illness. Ocular surface disorders are frequently developed by patients getting treatment for primary open-angle glaucoma or ocular hypotension. which are less prevalent and serious in geriatric patients because their use greater drugs and have greater advanced glaucoma.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Tinea pseudoimbricata: observations from a clinicoepidemiological and mycological study from eastern India.

The characteristic ring with ring appearance in patients with dermatophytosis should raise the suspicion of application of topical corticosteroids (alone or in combination with topical antifungals). Such patients be counselled about the harmful effects applying such inappropriate combinaiton.

Association of Serum Ferritin Levels with Microalbuminuria, Glycemic Control and Dyslipidemia.

As diabetes is on the rise worldwide, early screening and detection of its complications is crucial. The first clinical sign of renal dysfunction in diabetes is microalbuminuria. Ferritin may have a possible role in the development and prediction of microalbuminuria and other complications of diabetes by 3 possible mechanisms- 1) it is a marker of elevated body iron stores. 2) acts as acute-phase reactant and elevation reflects inflammation 3) Delayed clearance of glycosylated ferritin in patients with diabetes causes raised ferritin levels. In this premise, we studied the association between serum ferritin levels and microalbuminuria, glycemic control and dyslipidemia in type 2 diabetic patients. MATERIAL: A cross-sectional study was carried out at a tertiary hospital in northern India involving 152 patients of type 2 diabetes mellitus. Anthropometric measurements (weight, height), sample collection for basic laboratory parameters including complete blood count, kidney function tests, liver function tests, HbA1c, lipid profile, serum iron and ferritin levels, urinary albumin- creatinine ratio was done. A fundus examination was performed. Results were analyzed using descriptive statistics and making comparisons among various groups. Categorical data were summarized as proportions or percentages while discrete as mean. Chi-square test was used for testing associations. OBSERVATION: Mean serum ferritin levels were significantly higher in patients having microalbuminuria as against patients having normal urinary albumin- creatinine ratio (539 vs 292, p-value- 0.04). Patients having poor glycemic control (HbA1c > 7) had higher ferritin levels (p-value- 0.024). There was a near-significant association (p-value-0.06) between serum ferritin and triglyceride levels. More cases with raised serum ferritin had higher triglyceride levels. Patients having microalbuminuria had a higher prevalence of diabetic retinopathy (p-value- 0.003) and higher triglyceride levels (p-value- 0.041). CONCLUSION: Ferritin can act as a marker of diabetic nephropathy, poor glycemic control and dyslipidemia in type 2 diabetic patients. Our study, therefore, indicates that programs to prevent complications of diabetes would be more effective by placing greater emphasis on patients having higher ferritin levels.

Thrombocytopenia as a Prognostic Marker in Patients with Acute Encephalitis at a Tertiary Care Centre in Northern India.

Encephalitis is challenging to manage given the diversity of clinical and epidemiologic features. Various predictors of outcome have been studied so far including thrombocytopenia, cerebral edema, hypoglycaemia, development of status epilepticus and need for endotracheal intubation. Thrombocytopenia represents one of the potentially modifiable risk factors for poor prognosis in encephalitis. A better understanding of the epidemiology of this devastating disease and identification of predictors of outcome and management of reversible factors will pave the way for better management of the disease. MATERIAL: A total of 98 Hospitalised patients of Acute Encephalitis were enrolled in the study. Diagnoses were confirmed by CSF and Neuroimaging studies. Platelet count <150,000/cumm was considered as thrombocytopenia. Mild, moderate and severe thrombocytopenia was categorized at platelet count 100,000-150,000, 50,000-100,000 and <50,000/ cumm, respectively. Outcome at discharge was assessed using the Modified Ranking Score, categorized into 3 groups - good (0-2), fair (3-4), and poor (5-6). Chi-square, ANOVA and Independent samples 't'-tests were used to compare the data. OBSERVATION: Mean age of patients was 34.06±18.76 (range 14-85) years. Majority of patients were males (54.1). Mean GCS at admission was 9.41±1.90. Acute viral encephalitis(unclassified) (n=33; 33.7%), Scrub typhus (n=24; 24.5%) and Japanese encephalitis virus (n=12; 12.2%) were the most common underlying etiologies. A total of 74 (75.5%) patients had thrombocytopenia. Mild, moderate and severe thrombocytopenia was seen in 34 (34.7%), 30 (30.6%) and 10 (10.2%) cases. Thrombocytopenia was significantly higher in Dengue and Scrub as compared to other etiologies. Thrombocytopenia and its severity showed a significant association with lower GCS and higher mRS scores indicating a poor outcome. CONCLUSION: Thrombocytopenia is associated with a poor clinical status and adverse outcomes in patients with encephalitis of all causes.

Endophyte roles in nutrient acquisition, root system architecture development and oxidative stress tolerance.

Plants associate with communities of microbes (bacteria and fungi) that play critical roles in plant development, nutrient acquisition and oxidative stress tolerance. The major share of plant microbiota is endophytes which inhabit plant tissues and help them in various capacities. In this article, we have reviewed what is presently known with regard to how endophytic microbes interact with plants to modulate root development, branching, root hair formation and their implications in overall plant development. Endophytic microbes link the interactions of plants, rhizospheric microbes and soil to promote nutrient solubilization and further vectoring these nutrients to the plant roots making the soil-plant-microbe continuum. Further, plant roots internalize microbes and oxidatively extract nutrients from microbes in the rhizophagy cycle. The oxidative interactions between endophytes and plants result in the acquisition of nutrients by plants and are also instrumental in oxidative stress tolerance of plants. It is evident that plants actively cultivate microbes internally, on surfaces and in soils to acquire nutrients, modulate development and improve health. Understanding this continuum could be of greater significance in connecting endophytes with the hidden half of the plant that can also be harnessed in applied terms to enhance nutrient acquisition through the development of favourable root system architecture for sustainable production under stress conditions.

Malathion biodegradation by a psychrotolerant bacteria Ochrobactrum sp. M1D and metabolic pathway analysis.

An organophosphorus pesticide malathion biodegradation was investigated by using the bacteria Ochrobactrum sp. M1D isolated from a soil sample of peach orchards in Palampur, District Kangra, Himachal Pradesh (India). The bacterium was able to utilize malathion as the sole source of carbon and energy. The isolated bacterium was found psychrotolerant and could degrade 100% of 100 mg l-1 malathion in minimal salt medium at 20°C, pH 7·0 within 12 days with no major significant metabolites left at the end of the study. Through GCMS analysis, methyl phosphate, diethyl maleate, and diethyl 2-mercaptosuccinate were detected and identified as the major pathway metabolites. Based on the GCMS profile, three probable degradation pathways were interpreted. The present study is the first report of malathion biodegradation at both the psychrophilic and mesophilic conditions by any psychrotolerant strain and also through multiple degradation pathways. In the future, the strain can be explored to bio-remediate the malathion contaminated soil in the cold climatic region and to utilize the enzymatic systems for advanced biotechnology applications.

Pregnancy outcomes in women with primary biliary cholangitis and primary sclerosing cholangitis: a retrospective cohort study.

OBJECTIVE: To determine maternal, obstetric and neonatal outcomes in a cohort of women with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). DESIGN: Retrospective cohort study. SETTING: Ten specialist centres managing pregnant women with liver disease. POPULATION: Women with a diagnosis of PBC and PSC and a pregnancy of ≥20 completed weeks of gestation. METHODS: Retrospective case notes review. MAIN OUTCOME MEASURES: Adverse outcomes were defined as: maternal - development of ascites, variceal bleeding, encephalopathy and jaundice; obstetric events - gestational hypertension, pre-eclampsia and postpartum haemorrhage; and neonatal - stillbirth, preterm delivery and admission to neonatal unit. The relationship of alanine transferase (ALT) and bile acid levels with gestation at delivery was studied. RESULTS: The first recorded pregnancies of 34 women with PSC and 27 women with PBC were analysed. There were 60 live births and one intrapartum stillbirth that did not occur in the context of maternal cholestasis. The overall median gestation of delivery was 38 weeks but the rate of preterm birth was 28% (17/61 deliveries), 76% (13/17) of which were spontaneous. Gestation at birth negatively correlated with maternal serum ALT concentration at booking (P = 0.017) and serum bile acid concentration during pregnancy (P = 0.016). There were no other significant correlations and maternal and neonatal outcomes were good. CONCLUSIONS: Pregnancy in PBC and PSC is well tolerated, but women should be counselled regarding the increased risk of preterm birth. Measurement of maternal ALT and bile acids may help identify women at risk of preterm delivery. TWEETABLE ABSTRACT: Pregnancy in women with PBC and PSC is well tolerated; however, rates of preterm birth are high and are related to maternal bile acid levels.

White-tailed deer (Odocoileus virginianus) are a reservoir of a diversity of Toxoplasma gondii strains in the USA and pose a risk to consumers of undercooked venison.

To assess the role of white-tailed deer (Odocoileus virginianus, WTD) in the epidemiology of toxoplasmosis, we conducted a national survey of WTD across the USA for Toxoplasma gondii infection. To do this, we combined serology with parasite isolation to evaluate the prevalence and genetic diversity of T. gondii in this game species. From October 2012 to March 2019, serum and tissues were collected from 914 WTD across the USA. Serum samples were screened for antibodies to T. gondii, and then the tissues of seropositive WTD were bioassayed in mice. Antibodies were detected in 329 (36%) of 914 WTD tested by the modified agglutination test (positive reaction at 1:25 or higher). Viable T. gondii was isolated from the heart of 36 WTD from 11 states. Three of the 36 isolates were pathogenic but not highly virulent to outbred Swiss Webster mice and all 36 isolates could be propagated further in cell culture and were genotyped. For genotyping, DNA extracted from cell culture-derived tachyzoites was characterized by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the genetic markers SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. Genotyping revealed seven ToxoDB PCR-RFLP genotypes, including 24 isolates for genotype #5 (haplogroup 12), four isolates for #2 (type III, haplogroup 3), three isolates for genotypes #1 (type II, haplogroup 2), two isolates for genotypes #3 (type II, haplogroup 2) and one isolate each for #39, #221 and #224. Genotype #5 was the most frequently isolated, accounting for 66.6% (24 of 36) of the isolates. Combining the 36 isolates from this study with previously reported 69 isolates from WTD, 15 genotypes have been identified. Among these, 50.4% (53/105) isolates belong to genotype #5. Our results indicate moderate genetic diversity of T. gondii in WTD. The results also indicate that undercooked venison should not be consumed by humans or fed to cats.

Genotyping of viable Toxoplasma gondii from the first national survey of feral swine revealed evidence for sylvatic transmission cycle, and presence of highly virulent parasite genotypes.

Feral swine are known reservoirs of various pathogens, including Toxoplasma gondii. Here, we report the first national survey of viable T. gondii in feral swine in the USA. We paired serological surveys with parasite isolation and bioassay to evaluate the prevalence and genetic diversity of these parasites. From 2012-2017, sera and tissues from 1517 feral swine across the USA were collected for the isolation of viable T. gondii. Serum samples were initially screened for antibodies to T. gondii, and then the tissues of seropositive feral swine were bioassayed in mice. Antibodies were detected in 27.7% of feral swine tested by the modified agglutination test (1:25 or higher). Antibody positive rates increased significantly with age, with 10.1% of juveniles, 16.0% of sub-adults and 38.4% of adults testing seropositive. Myocardium (50 g) from 232 seropositive feral swine was digested in pepsin and bioassayed in mice. Viable T. gondii was isolated from 78 feral swine from 21 states. Twelve of the 78 isolates were pathogenic to outbred Swiss Webster mice and 76 of the 78 isolates could be propagated further in cell culture and were genotyped. For genotyping, deoxyribonucleic acid extracted from cell culture-derived tachyzoites was characterized by polymerase chain reaction restriction fragment length polymorphism using the genetic markers SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. Genotyping revealed 15 ToxoDB genotypes, including 43 isolates for genotype #5 (haplogroup 12), 11 isolates for #24, four isolates for #2 (haplogroup 3), two isolates for each of genotypes #3 (haplogroup 2), #4 (haplogroup 12), #216, #221, #289 and #297 and one isolate for each of genotypes #1 (haplogroup 2), #39, #66, #260, #261 and #299. Genotype #5 was the most frequently isolated, accounted for 57% (43/76) of the isolates, followed by #24, accounted for 14% (11/76). Genotypes #260, #289, #297 and #299 are new types. Genotype #289 was highly virulent to mice and originated from feral swine collected in Louisiana on the same day at the same location. Genotype #216 was previously demonstrated to be highly virulent to mice. Our results indicate moderate genetic diversity of T. gondii in feral swine in the USA, with the genotype #5 (haplogroup 12) dominant in the continental USA, whereas genotype #24 (10/14) was dominant in Hawaii, suggesting different population structures of the parasites among the two distinct geographical locations.

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Prevalence and clinical characteristics of itch in epidemic-like scenario of dermatophytoses in India: a cross-sectional study.

BACKGROUND: Itch is an integral part of clinical picture of superficial dermatophytoses which constitute a common and growing problem in India. OBJECTIVES: The study aimed to evaluate the prevalence, intensity and clinical characteristics of itch in superficial dermatophytosis. METHODS: The data concerning disease history and clinical type of dermatophytosis were obtained. The presence and various characteristics of itch were documented. Numerical Rating Scale (NRS) was utilized to assess the worst intensity of itch during the last 3 days and during the course of the disease. 4-Item Itch Questionnaire was utilized to assess itch extent, intensity, frequency and associated sleep impairment, while quality of life (QoL) impairment was assessed via Dermatology Life Quality Index. RESULTS: Ninety-nine patients with direct microscopic confirmation of dermatophytosis were included in the study. In 46.5% of subjects, the coexistence of tinea corporis and tinea cruris was noted, followed by tinea cruris (25.2%) and tinea corporis (13.1%). The majority of patients reported itch in the last 3 days (99%) and complained of itch limited to skin lesions (89.9%). According to NRS, the mean intensity of worst itch in the last 3 days was 6.8 ± 1.8 points. Severe and very severe itch was reported by 74.7% of patients. Itch was an isolated sensation in 34.3% of subjects, while 46.9% reported associated burning sensation. Itch was frequently exacerbated by sweating, hot temperature and wearing tight clothes. Difficulties in falling asleep and sleep awakenings were reported by 34.3% and 54.6% of subjects, respectively. Itch negatively influenced the well-being of patients and its intensity correlated with QoL impairment. CONCLUSIONS: Itch is an important symptom in superficial dermatophytoses and is associated with negative impact on sleep and carries a significant psychosocial burden. Acknowledging its presence is necessary in a holistic approach to these patients.

Aspergillus sensitization in bronchial asthma: A separate phenotype.

Background: Bronchial asthma is one of the common chronic respiratory illnesses worldwide, with a global disease burden that affects approximately 300 million individuals. It affects 5-10% of the population in developed countries. India constitutes approximately one-tenth of the global disease burden, where an estimated 7 million children are affected by this illness. Airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. In India, the most important endogenous stimuli is considered to be fungal antigens from the genus, Aspergillus. Positive skin reactions to Aspergillus fumigatus among individuals with atopic asthma is 10 to 20%; however, a causal relationship is yet to be established. A separate entity, termed "severe asthma with fungal sensitivity," is often used to describe milder allergic reactions to fungal aeroallergens that has fungal sensitization as the starting point of pathogenesis than allergic bronchopulmonary aspergillosis. Methods: A total of 57 patients with bronchial asthma were prospectively enrolled and evaluated for Aspergillus sensitization and its impact on asthma control. Results: Symptoms were well controlled in a majority of patients (57.89%) and partly controlled in 14.04%. Uncontrolled symptoms were observed in only 28.07% of patients. The proportion of patients with uncontrolled symptoms was higher among patients who were sensitized (45.00%) compared with patients who were not sensitized (18.92%). The proportion of patients with well-controlled symptoms was higher in individuals who were not sensitized compared with individuals who were sensitized (62.16% versus 50.00%). Conclusion: The severity of asthma was associated with fungal sensitization, with sensitization to Aspergillus as a part of the pathogenesis. Aspergillus sensitization is significantly associated with bronchiectasis, even in the absence of clinical features.

Feeding status of free-range scavenging chickens in different agro-climatic regions of India.

1. The aim of this study was to determine the nutritional status of backyard chickens reared under 4 different agro-climatic conditions (tropical, humid subtropical, cool-temperate and semi-arid) of India during different seasons of the year and to compare their nutritional status with those reared under confined feeding system (CFS). In each season, 15 adult and 15 grower chickens were slaughtered for collecting content of crop and gizzard to assess the nutritional status from different agro-climatic conditions.2. The dry matter content of crop and gizzard was higher (P < 0.01) in chickens reared under backyard conditions compared to those reared under CFS.3. Higher (P < 0.01) crop and gizzard contents were recorded during winter compared to the rainy season. The proportion of grains in the crop during summer and winter season was higher compared to rainy season. Further, there were more insects present in the crop during the rainy season and winter compared to summer.4. The proportion of insects was higher in chickens reared in humid, subtropical and cool temperate regions compared to semi-arid conditions. The consumption of grasses was higher in cool-temperate regions as compared to those reared under other areas.5. Crude protein (CP), Ca, P and gross energy (GE) content of the crop were higher in chickens reared under CFS compared to those reared in backyard systems and CP in the crop contents was lower in backyard chickens reared in humid subtropical and semi-arid regions compared to other areas. Similarly, lower (P < 0.01) Ca levels were seen in crop and gizzard contents from birds reared in semi-arid Rajasthan, and P and GE were lower in tropical wet and dry Telangana (TWT) compared to the chickens reared in the backyard conditions in other regions.6. Based on the results, the nutrient intake for birds utilising the scavenging feed resource base (SFRB) in the TWT region was below the requirements of backyard chickens from the other regions selected in the present study. GE and CP were critically deficient in the SFRB of the TWT region. Therefore, evolving location-specific supplementary diets using locally available feed resources to meet nutrient requirement of backyard chickens is required for optimising production potential.

Treatment of heart failure with sodium glucose co-transporter-2 inhibitors in people with type 2 diabetes mellitus: current evidence and future directions.

Diabetes is one the most common comorbidities among people with established heart failure. Interest in heart failure as an outcome among people with diabetes has emerged since it was shown that there was an association between increased risk of hospitalization for heart failure with use of thiazolidinediones and some dipeptidyl peptidase-4 inhibitors. Recently, sodium-glucose co-transporter-2 inhibitors were shown to lead to a reduction in the risk of cardiovascular death and hospitalization for heart failure in people with Type 2 diabetes mellitus and either cardiovascular risk factors or atherosclerotic cardiovascular disease. These findings appear to be consistent in people both with and without a baseline history of heart failure. Based on current evidence there are several clinical scenarios in which the use of sodium-glucose co-transporter-2 inhibitors would be justified for people with heart failure and atherosclerotic cardiovascular disease: (1) in people with a new diagnosis of Type 2 diabetes and for whom anti-hyperglycaemic management strategies are being considered; (2) in people with sub-optimal glycaemic control, regardless of baseline antihyperglycaemic therapy; and (3) in people with symptomatic heart failure (or other high-risk features such as recent hospitalization for heart failure), if glycaemic control is optimized and the individual is on a sulfonylurea or dipeptidyl peptidase-4 inhibitor; here, it may be reasonable to consider substituting one of those therapies for a sodium-glucose co-transporter-2 inhibitor. There are now a number of ongoing trials evaluating the role of sodium-glucose co-transporter-2 inhibitors as therapy for people with established heart failure (with preserved or with reduced ejection fraction) and regardless of the presence of diabetes. These trials will provide the evidence for the safety and efficacy of sodium-glucose co-transporter-2 inhibitors among people with established heart failure.

Prostate biopsy: when and how to perform.

Prostate cancer, unlike other cancers, has been sampled in a non-targeted, systematic manner in the past three decades. On account of the low volume of prostate sampled despite the multiple cores acquired, systematic transrectal (TRUS) biopsy suffered from low sensitivity in picking up clinically significant prostate cancer. In addition, a significant number of cancers of the anterior, lateral peripheral zone, and the apex were missed as these areas were undersampled or missed during this biopsy protocol. Subsequently, the number of cores acquired was increased with special focus given to targeting the previously undersampled areas. These procedures led to an increase in the complication rates as well as detection of more clinically insignificant cancers. The advent of multiparametric magnetic resonance imaging (MRI) and its high intrinsic tissue contrast enabled better detection of prostate cancer. This led to the introduction of MRI-targeted biopsies with either MRI-TRUS fusion or under direct (in-gantry) guidance. MRI-targeted biopsies increased the percentage of positive cores and detection of clinically significant prostate cancers; however, these are expensive, time-intensive, require significant capital investment and operator expertise. This article describes the indications, workflow, complications, advantages, and disadvantages of TRUS-guided biopsy followed by MRI-guided biopsies.

Cancer Pain, Anxiety, and Depression in Admitted Patients at a Tertiary Care Hospital: A Prospective Observational Study.

CONTEXT: Pain is the most common symptom in admitted cancer patients. The association between the severity of cancer pain and distress symptoms such as depression and anxiety is a subject of research. AIMS: The aim is to study the prevalence of pain, anxiety, and depression in admitted cancer patients and determine the association between pain and anxiety and depression at a tertiary cancer care institute. SETTINGS AND DESIGN: This was prospective observational study. SUBJECTS AND METHODS: We enrolled 393 cancer inpatients prospectively after written informed consent. Their disease details, presence, severity, and character of pain were recorded. Numerical Pain Scale was used for pain scores, self-reporting Hospital Anxiety and Depression Scale for anxiety and depression. STATISTICAL ANALYSIS USED: Normal data were analyzed with parametric, nonnormal with nonparametric methods, and categorical with the Chi-square test. RESULTS: The prevalence of moderate-to-severe pain was 41.5%, anxiety 20.3%, and depression 24.8%. Proportion of patients with anxiety and depression was 9.2% and 17.7% in patients with no pain; about 32.8% and 36.7% with severe pain, respectively (P < 0.000). In patients with no depression 6% had anxiety; with depression 44.9% had anxiety (P < 0.000). Odd's ratio to have anxiety and depression was 4.44 (95% confidence interval [CI] 2.0318-9.7024) and 2.92 (95% CI 1.5739-5.4186), respectively, in patients with pain as compared to no pain (P < 0.00). There was a positive correlation between pain, anxiety, and depression scores. CONCLUSIONS: There is strong association between the presence and severity of pain and distress symptoms such as anxiety and depression in admitted cancer patients.

Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial.

Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients. Patients and methods: We carried out a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events. Results: In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of whom 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin [hazard ratio (HR), 1.11; 95% confidence interval (CI) 0.89-1.38; P = 0.36 and HR, 1.18; 95% CI 0.95-1.46; P = 0.14, respectively]. Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR, 0.31; 95% CI 0.11-0.84; P = 0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms. Conclusion: LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted.