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1.
Eur Respir J ; 63(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423624

RESUMO

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergilose Pulmonar Invasiva , Adulto , Criança , Humanos , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Imunoglobulina E , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Itraconazol/uso terapêutico , Micologia , Prednisolona
2.
Mycoses ; 67(5): e13745, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767273

RESUMO

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.


Assuntos
COVID-19 , Coinfecção , Mucormicose , Humanos , COVID-19/complicações , COVID-19/mortalidade , Mucormicose/mortalidade , Mucormicose/epidemiologia , Mucormicose/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prevalência , Coinfecção/mortalidade , Coinfecção/epidemiologia , Coinfecção/microbiologia , Índia/epidemiologia , Adulto , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/mortalidade , Aspergilose Pulmonar/epidemiologia , SARS-CoV-2 , Idoso , Estudos de Casos e Controles , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/epidemiologia
3.
J Assoc Physicians India ; 72(1): 18-21, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38736069

RESUMO

INTRODUCTION: The world has changed tremendously for patients suffering from diabetes mellitus with the development of cutting-edge technologies like continuous glucose monitoring and flash glucose monitoring systems. Now, the details of constant fluctuations of glucose in their blood can be monitored not only by medical professionals but also by patients, and this is called glycemic variability (GV). Traditional metrics of glycemic control measurement, such as glycated hemoglobin (HbA1c), fail to reflect various short-term glycemic changes like postprandial hyperglycemia and hypoglycemic episodes, paving the way to the occurrence of various diabetic complications even in asymptomatic, well-controlled diabetic patients. This need for advanced management of diabetes and effective monitoring of these swings in blood glucose can be met by using a continuous glucose monitoring system (CGMS). AIM AND OBJECTIVE: To evaluate the extent of GV in well-controlled type 2 diabetes mellitus (T2DM) patients using a flash CGMS and to assess the correlation between GV and HbA1c. MATERIALS AND METHODS: A hospital-based prospective observational study was carried out from May 2020 to Oct 2021 at the Department of Medicine, SMS Hospital, Jaipur, Rajasthan (India), after approval from the Ethics Committee of the institution. A total of 30 patients with well-controlled T2DM (HbA1c was ≥6.5, but ≤7.5) were included in the study using simple random techniques after written informed consent from patients. Patients were studied for glycemic excursions over a period of 7 days by using FreeStyle® Libre Pro™, which is a flash glucose monitoring system. The CGM sensor was attached to the left upper arm of the patient on day 0 and removed on day 7. The data recorded in the sensor was then retrieved using pre-installed computer software and analyzed using standard CGM metrics like standard deviation (SD), percentage coefficient of variation (%CV), time above range (TAR), time below range (TBR), and time in range (TIR), out of which %CV was used to quantify GV. %CV has been used to cluster patients into four cohorts from best to worst, namely: best/low CV ≤ 10%, intermediate CV from 10 to 20%, high CV from 20 to 30%, and very high CV of >30%. Scatterplots are used to establish correlations between various parameters. RESULT: Data from a total of 30 patients were analyzed using CGMS and thus used for calculating standard CGM metrics; glucose readings every 15 minutes were recorded consecutively for 7-day periods, making it a total of 672 readings for each patient. Interpreting the CGM data of all 30 patients, the following results were found: the mean blood glucose of all cases is 134.925 ± 22.323 mg/dL, the mean SD of blood glucose of all cases is 35.348 ± 9.388 mg/dL, the mean of %CV of all cases is 26.376 ± 6.193%. CGM parameters of time are used in the form of percentages, and the following results were found: the mean of TAR, TBR, and TIR is 14.425 ± 13.211, 5.771 ± 6.808, and 82.594 ± 12.888%, respectively. Clustering the patients into cohorts, the proportion of patients exhibiting best/low %CV (10%) is 0, intermediate %CV (10-20%) is 16.67% (five out of 30 patients), high %CV (20-30%) is 50% (15 out of 30 patients) and very high %CV (>30%) is 33.33% (10 out of 30 patients). Also, there is no significant correlation found between HbA1c and %CV (ρ = 0.076, p-value = 0.690); a significant negative correlation was found between %CV and TIR (ρ = -0.604, p < 0.001S); a positive correlation of %CV with TAR and TBR is significant (ρ = 0.816, p-value of <0.001). CONCLUSION: Using a flash CGMS device and considering %CV as the parameter and primary measure of GV, the study demonstrated the overall instability of a person's glycemic control, making note of unrecognized events of hypoglycemia and hyperglycemia in asymptomatic well-controlled T2DM patients, revealing the overall volatile glycemic control. The most important finding of this study is that even those diabetics who are considered well-controlled experience a great degree of GV as assessed by CGM-derived metrics. This study also demonstrated that there is no significant correlation between HbA1c and GV, suggesting that patients may not have optimal control of their diabetes despite having "normal HbA1c" values; hence, GV can be considered an HbA1c-independent danger factor, having more harmful effects than sustained hyperglycemia in the growth of diabetic complications. So, by using CGM-derived metrics, the measurement of GV has the potential to complement HbA1c data. In this manner, a more comprehensive assessment of glycemic excursions can be provided for better treatment decisions, thereby facilitating optimal glycemic control, which is essential for reducing overall complications and promoting good quality of life.


Assuntos
Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Humanos , Diabetes Mellitus Tipo 2/sangue , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/instrumentação , Glicemia/análise , Hemoglobinas Glicadas/análise , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Controle Glicêmico/métodos , Adulto , Idoso , Monitoramento Contínuo da Glicose
4.
J Assoc Physicians India ; 72(3): 24-26, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38736112

RESUMO

AIM AND OBJECTIVE: To assess the relationship between glycated hemoglobin (HbA1c) with inflammatory markers, neutrophil-to-lymphocytes ratio (NLR), and monocyte-to-lymphocytes ratio (MLR) in controlled and uncontrolled type 2 diabetes patients. MATERIALS AND METHODS: This was a hospital-based cross-sectional study conducted at the Department of Medicine, SMS Hospital, and an attached group of hospitals (Jaipur, Rajasthan, India) after informed consent from the Ethics Committee of the institute. After obtaining informed consent from patients who met the inclusion and exclusion criteria, 200 diabetic patients were included in the study using the simple randomization method. Following a detailed history and diagnosis, vital demographic information, and blood tests were collected from patients via a predesigned preliminary questionnaire. The following blood tests were collected: white blood cell (WBC), Hb, hematocrit (HCT), red cell distribution width (RDW), neutrophils, lymphocytes, HbA1c, blood glucose, NLR ratio, and MLR ratio. Data were entered and analyzed using Statistical Package for the Social Sciences version 22. RESULTS: The mean age of patients with controlled diabetes mellitus was 54.10 years, while that of patients with uncontrolled diabetes mellitus was 55.3 years. Glycemic control was more in the age group of 51-60 years. Around 54% of males and 46% of females were included in the present study, and no association was found between the two genders with poor and good glycemic control. Around 63.29% of participants with uncontrolled diabetes have an increased NLR, and 61.39% of participants with uncontrolled diabetes have an increased MLR. A strong association was found between the NLR and MLR with the glycemic control. CONCLUSION: Uncontrolled diabetes mellitus had a positive association with inflammatory markers, that is, NLR and MLR. STATEMENT OF SIGNIFICANCE: Diabetes mellitus is the most common metabolic disorder in Asian countries. It leads to many acute and chronic complications in uncontrolled diabetes. Markers like the NLR ratio and MLR ratio are inexpensive and easily available for blood investigation. Hence, these markers are quite useful in differentiating controlled and uncontrolled diabetes and, therefore, useful in predicting blood sugar control in type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Linfócitos , Monócitos , Neutrófilos , Humanos , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Transversais , Biomarcadores/sangue , Adulto , Idoso , Índia , Glicemia/análise
5.
Monaldi Arch Chest Dis ; 94(1)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194448

RESUMO

During and following the COVID-19 pandemic, the world has witnessed a surge in high-flow oxygen therapy (HFOT) use. The ability to provide high oxygenation levels with remarkable comfort levels has been the grounds for the same. Despite the advantages, delays in intubation leading to poor overall outcomes have been noticed in subgroups of patients on HFOT. The respiratory rate-oxygenation (ROX) index has been proposed to be a useful indicator to predict HFOT success. In this study, we have examined the utility of the ROX index prospectively in cases of acute hypoxemic respiratory failure (AHRF) due to infective etiologies. A total of 70 participants were screened, and 55 were recruited for the study. The majority of participants were males (56.4%), with diabetes mellitus being the most common comorbidity (29.1%). The mean age of the study subjects was 46.27±15.6 years. COVID-19 (70.9%) was the most common etiology for AHRF, followed by scrub typhus (21.8%). 19 (34.5%) experienced HFOT failure, and 9 (16.4%) subjects died during the study period. Demographic characteristics did not differ between either of the two groups (HFOT success versus failure and survived group versus expired group). The ROX index was significantly different between the HFOT success versus failure group at baseline, 2, 4, 6, 12, and 24 hours. The best cut-offs of the ROX index at baseline and 2 hours were 4.4 (sensitivity 91.7%, specificity 86.7%) and 4.3 (sensitivity 94.4% and specificity 86.7%), respectively. The ROX index was found to be an efficient tool in predicting HFOT failure in cases of AHRF with infective etiology.


Assuntos
COVID-19 , Insuficiência Respiratória , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Taxa Respiratória , Pandemias , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Oxigenoterapia , COVID-19/complicações , Oxigênio/uso terapêutico
6.
J Assoc Physicians India ; 71(11): 30-35, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38720493

RESUMO

Background: Hypertension is a major public health issue in India. Early detection and management of high blood pressure (BP) is crucial, especially among young adults. This study aimed to estimate the prevalence of obesity and hypertension among undergraduate medical students. Materials and methods: A cross-sectional study was conducted among 450 first year undergraduate medical students aged 18-25 years in S.M.S. Medical and Hospital Jaipur, Rajasthan after clearance from institutional ethics committee and written consent from participants. Anthropometric measurements like height, weight, BMI, waist circumference, hip circumference and blood pressure were recorded. Hypertension was defined as per JNC VIII guidelines. Data was analyzed using appropriate statistical tests. Results: Overall, 15.56% students were hypertensive and 40.67% were prehypertensive. Hypertension was more prevalent in males (18.83%) compared to females (12.33%) (p = 0.002). Overweight/obesity was present in 29.33% students, more common in males (37.67%) than females (21.15%) (p < 0.001). Obese students had higher rates of prehypertension (47%) and hypertension (28.8%). Abnormal waist-hip ratio and waist-stature ratio were significantly associated with hypertension (p < 0.001). Conclusion: Overweight/obesity and hypertension are highly prevalent among undergraduate medical students, especially males. Unhealthy lifestyles and risk factors need to be addressed to prevent long term morbidity. Routine screening and health promotion activities should be conducted for this high risk group. How to cite this article: Sharda K, Saxena P, Yadav SK, et al. To Estimate the Prevalence of Obesity and High Blood Pressure among Undergraduate Students at a University Medical Institution in North India. J Assoc Physicians India 2023;71(11):30-35.


Assuntos
Hipertensão , Obesidade , Estudantes de Medicina , Humanos , Índia/epidemiologia , Masculino , Feminino , Estudantes de Medicina/estatística & dados numéricos , Hipertensão/epidemiologia , Estudos Transversais , Adulto Jovem , Prevalência , Adulto , Obesidade/epidemiologia , Adolescente , Pré-Hipertensão/epidemiologia , Universidades , Fatores de Risco
7.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443412

RESUMO

Tuberculosis is one of the oldest diseases known to affect humans and the top cause of infectious death worldwide caused by M. tuberculosis complex. Tuberculosis may be pulmonary, extra-pulmonary or both. Nervous system tuberculosis is relatively rare and has protean nature of symptoms so poses diagnostic difficulty. Neurological manifestations of tuberculosis includes 1) intracranial 2) spinal 3) peripheral nerve tuberculosis. Central nervous system tuberculosis accounts about 5% of extra pulmonary cases and 1% all tuberculosis. MATERIAL: Here we are presenting the series of 10 cases which have wide variety of neuropathogenic nature of tuberculosis. OBSERVATION: Here we are presenting the series of 10 cases which have wide variety of neuropathogenic nature of tuberculosis. These includes 1) Tubercular cortical vein thrombosis -patient who is a known case of pulmonary tuberculosis presented with severe headache, seizure and altered behavior, MRI brain shows cortical vein thrombosis and normal coagulation profile (Review of literature shows only 4 cases). 2)Tubercular myelitis/ arachnoiditis-presented with low backache and bilateral lower limb weakness,CSF panel and MRI L S spine shows tubercular arachnoiditis/myelitis. 3)Tubercular peripheral neuropathy; patient who is a non- diabetic presented with pain abdomen and bilateral lower limb tingling and numbness with no past history of treatment with anti-tubercular drug, CECT abdomen shows ileocecal tuberculosis and NCS study shows sensory affection of lower limb nerve. 4)Tuberculoma-patient presented with severe headache, seizure and altered behavior, MRI brain shows tuberculoma. 5) and 6) are tubercular vascular infarct in 1 of these 2 cases patient was having multiple necrotic foci and few foci of cavitation in left hilar region which is extending into left inferior pulmonary vein and even reaching upto left atrium. 7) and 8) cases are pott's spine who presented with low backache. 9) and 10) are tubercular meningitis and tubercular meningitis with hydrocephalus respectively. These patients were treated according to their diagnosis and for focal neurological deficit physiotherapy was advised. Except a case of septic foci emboli from left atrium which shows moderate recovery rest all cases shows good recovery at discharge. CONCLUSION: There is paucity of literature on neuropathogenic nature of tuberculosis. In this case series we are presenting the series of 10 cases of tubercular nervous system manifestations so that it will helps to diagnose the disease as early as possible and allows us to initiate the prompt treatment so that we can mitigate the significant morbidity and mortality among survivors of nervous system tubercular disease.


Assuntos
Aracnoidite , Dor Lombar , Mielite , Tuberculoma , Tuberculose Meníngea , Cefaleia/etiologia , Humanos , Convulsões/etiologia , Tuberculose Meníngea/complicações , Tuberculose Meníngea/diagnóstico
8.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443430

RESUMO

Sjogren syndrome is an autoimmune disease characterised by lymphocytic infiltration and inflammation of the exocrine glands resulting in decreased secretion of involved glands which manifests mostly as dry eye and dry mouth. The prevalence of the disease is reported to be about 10.3 per 10,000 population. It is more common in females with a male: female ratio of 16:1. Extra glandular manifestations are seen in up to 1/3rd of the cases. Renal involvement is seen in 4.9% of patients with Sjogren syndrome. MATERIAL: Here we present three cases of Sjogren Syndrome who presented to our hospital with hypokalaemic quadriparesis. OBSERVATION: On evaluation all three of the patients were found to have renal tubular acidosis type 1. None of these patients had any symptom of Sjogren syndrome before the onset of quadriparesis. All of these patients had acute onset progressive areflexic quadriparesis with involvement of facial muscles and drooping of eyelids without sensory or bladder bowel involvement. One of these patients had respiratory muscle paralysis severe enough to mandate mechanical ventilation. Arterial Blood Gas analysis and urine electrolyte analysis were suggestive of type 1 renal tubular acidosis. ANA positive in 2 of the 3 patients. Anti-SSA & anti-SSB antibodies were positive in all three patients. Supportive measures and IV fluid and electrolyte correction was done. There was complete recovery of power in all three patients and were discharged on oral medications.Renal Tubular Acidosis is characterised by inability of the nephrons to maintain physiologic acid base balance. This usually results from a defect in the tubular transport mechanisms. Distal Renal tubular acidosis (as in these patients) is further defined by an alkalotic urinary pH(>5.5) and profound hypokalemia due to impairment in H+ secretion in ditstal tubular alpha-intercalated cells. Owing to this imbalance of ionic transport in distal tubules there can be nephrocalcinosis, nephrolithiasis, rickets and severe muscle weakness. Sjogren syndrome is one of the etiologies leading to development of T1RTA.T1RTA can be the presenting feature of Sjogren Syndrome. CONCLUSION: Though a rare manifestation of the disease if can be the presenting symptom. Work up for RTA (ABG, urine electrolytes, Urine PH and osmolarity etc) in patients with hypokalaemic paresis can help establish the etiological diagnosis(ANA, anti-SSA,anti-SSB) and help prevent future relapses of the disease.


Assuntos
Acidose Tubular Renal , Hipopotassemia , Síndrome de Sjogren , Acidose Tubular Renal/complicações , Acidose Tubular Renal/diagnóstico , Feminino , Humanos , Hipopotassemia/complicações , Masculino , Quadriplegia/complicações , Recidiva , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico
9.
Indian J Crit Care Med ; 25(6): 668-674, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34316147

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) is a common cause of hospitalization in high altitude areas with significant morbidity. The clinical presentation of HAPE can overlap with a broad spectrum of cardiopulmonary diseases. Also, it is associated with varied radiological manifestations mimicking other conditions and often leading to unnecessary and inappropriate treatment. PATIENTS AND METHODS: The primary aim of the study was to study the various radiological manifestations of HAPE through real-world chest radiographs. We present six different chest X-ray patterns of HAPE as a pictorial assay, at initial presentation, and after the resolution of symptoms with supplemental oxygen therapy and bed rest alone. RESULTS: HAPE can present as bilateral symmetrical perihilar opacities, bilateral symmetrical diffuse opacities, unilateral diffuse opacities, bilateral asymmetrical focal opacities, and even lobar consolidation with lower zone or less commonly upper zonal predilection. These presentations can mimic many common conditions like heart failure, acute respiratory distress syndrome, pulmonary embolism, aspiration pneumonitis, pneumonia, malignancy, and tuberculosis. CONCLUSION: A holistic clinical-radiological correlation coupled with analysis of the temporal course can help high-altitude physicians in differentiating true HAPE from its mimics. HOW TO CITE THIS ARTICLE: Yanamandra U, Vardhan V, Saxena P, Singh P, Gupta A, Mulajkar D, et al. Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay. Indian J Crit Care Med 2021;25(6):668-674.

10.
Curr Treat Options Oncol ; 21(11): 91, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920711

RESUMO

The original version of this article unfortunately contained mistakes. In Table 2, under the column 'Lead to death' in Row 5 [CheckMate-026], the figures should read as '0.7' for Experimental Arm and '1.1' for Comparator. Right now, these are printed as 0.007 and 0.011 respectively.

11.
Curr Treat Options Oncol ; 21(8): 69, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32720019

RESUMO

OPINION STATEMENT: Immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic and selected cases of unresectable advanced non-small cell lung cancer (NSCLC). Importantly for patients, this implies that in the absence of a targetable oncogenic driver [especially epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements] and in the presence of high programmed death-ligand 1 (PD-L1) expression (≥ 50%), they are eligible for mono-therapy with pembrolizumab thereby avoiding chemotherapy as the first line of treatment. This mono-immunotherapy approach for high PD-L1 metastatic NSCLC is associated with improved overall survival (OS) and radiological responses (RR) with lesser toxicity as compared with conventional platinum doublet chemotherapy for both non-squamous and squamous histological types.However, majority of NSCLC patients either have no or low expression of PD-L1 (< 50%) and such patients derive greater benefit from a combination of PD-1/PD-L1 ICIs with platinum doublet chemotherapy as compared with chemotherapy alone. Again, benefits are seen for both OS and RRs. However, combining immunotherapy with chemotherapy, in general, does lead to higher toxicity than those seen with either of the two alone.Additionally, for non-squamous NSCLC patients, clinicians should not initiate ICI treatment till the results of common targetable genetic alterations like EGFR mutation, ALK, and ROS1 gene rearrangement testing are known (preferably on broad next generation sequencing) and are negative (even if results of PD-L1 testing are available)-as targeted therapies remain the cornerstone of treatment for patients harboring these oncogenic drivers.It is worth mentioning that PD-1 and PD-L1 ICIs are very expensive, and their usage is associated with occurrence of immune-related adverse events (irAEs) which occasionally can be severe. Hence, it is important to discuss efficacy, toxicity, and cost-related to ICI treatment with each and every patient at diagnosis in order to help them decide if they are willing to go ahead with this form of therapy either singly (for high PD-L1 expressors) or in combination with chemotherapy (for others).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Algoritmos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Tomada de Decisão Clínica , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Proteínas de Checkpoint Imunológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento
12.
Molecules ; 24(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561530

RESUMO

Thymidylate synthase (TS) is a prominent drug target for different cancer types. However, the prolonged use of its classical inhibitors, substrate analogs that bind at the active site, leads to TS overexpression and drug resistance in the clinic. In the effort to identify anti-TS drugs with new modes of action and able to overcome platinum drug resistance in ovarian cancer, octapeptides with a new allosteric inhibition mechanism were identified as cancer cell growth inhibitors that do not cause TS overexpression. To improve the biological properties, 10 cyclic peptides (cPs) were designed from the lead peptides and synthesized. The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act as an allosteric inhibitor more potent than its parent open-chain peptide [Pro3]LR. In cytotoxicity studies on three human ovarian cancer cell lines, IGROV-1, A2780, and A2780/CP, peptide 5 and two other cPs, including 7, showed IC50 values comparable with those of the reference drug 5-fluorouracil, of the open-chain peptide [d-Gln4]LR, and of another seven prolyl derivatives of the lead peptide LR. These promising results indicate cP 7 as a possible lead compound to be chemically modified with the aim of improving both allosteric TS inhibitory activity and anticancer effectiveness.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Timidilato Sintase/antagonistas & inibidores , Sítio Alostérico , Sítios de Ligação , Linhagem Celular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ativação Enzimática , Humanos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
13.
J Assoc Physicians India ; 67(3): 60-62, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304708

RESUMO

BACKGROUND: It is accepted that metabolic syndrome increases the relative risk of cardiovascular disease and visceral adiposity lies at root of the cardio-metabolic risk. Upper body fat distribution has long been recognized as associated with metabolic syndrome and increased cardiovascular risk; hence the present study was conducted with the objective to evaluate the association of neck circumference with metabolic syndrome and cardiovascular risk factors. MATERIAL AND METHODS: The present study was a hospital based observational, Descriptive and comparative analysis, conducted at Department of General Medicine at a tertiary care centre of west India after Ethical clearance from the institute's ethical committee and written informed consent. A total of 405 subjects aged 18 - 60 years were selected consecutively after inclusion and exclusion criteria. Subjects were evaluated for metabolic syndrome components and cardiovascular risk factors. Neck circumference of ≥ 37 cm in males and ≥ 34 cm in females was considered abnormal. RESULTS: Metabolic syndrome was seen in 189 (46.7%) subjects. Raised triglyceride level was the most common (52.8%) component. Neck circumference was found to be statistically significant associated with metabolic syndrome (p<0.001) as well as cardiovascular risk factors like BMI, Waist circumference, Hypertension, Fasting blood sugar, TG and HDL were also found to be statistically significant associated with neck circumference. CONCLUSION: Neck Circumference can be used as a sensitive tool for metabolic syndrome and cardiovascular risk factors. Patients with abnormal Neck circumference should be screened for cardiovascular risk factors to detect abnormality for early and appropriate intervention.


Assuntos
Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Pescoço/anatomia & histologia , Adolescente , Adulto , Biometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
14.
Indian J Crit Care Med ; 23(9): 427-429, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31645829

RESUMO

Rhabdomyolysis is a serious medical condition, encountered in the intensive care unit (ICU). The etiology of rhabdomyolysis is often multifactorial. It leads to complications like acute kidney injury and life-threatening electrolyte abnormalities. A high index of suspicion and early institution of therapy is required to prevent complications and improve patient outcomes. Herein, we present the case of a young man with alcohol dependence who presented with fever and altered sensorium. He was found to have rhabdomyolysis and was managed successfully. We also discuss the common causes of rhabdomyolysis and a bedside approach to its management in the ICU. How to cite this article: Saxena P, Dhooria S, Agarwal R, Prasad KT, Sehgal IS. Rhabdomyolysis in Intensive Care Unit: More than One Cause. Indian J Crit Care Med 2019;23(9):427-429.

15.
J Cell Biochem ; 119(10): 8574-8587, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30058078

RESUMO

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase that plays a key role in HCV replication, and, hence, NS5B is an attractive target for hepatitis C drug discovery. Hepatitis C is a chronic liver disease affecting the global population significantly. Many NS5B inhibitors targeting active site were launched in recent years, however, still there exists a pressing need for cost-effective therapies with pan genotypic activity and therapies targeting niche HCV population with comorbities and resistant to earlier therapies. The objective of the current study is to identify potential anti-HCV agents from FDA approved drugs that are already in the market for a different disease-Drug repurposing approach. A combination of computational chemistry and computational biology techniques was used to discover potential therapies for hepatitis C targeting the NS5B Thumb I allosteric site. Computational chemistry analysis emphasized the fact that fluvastatin, a lipid lowering agent, and olopatadine, an antihistamine, exhibited good binding affinity to NS5B. In addition, gene set enrichment analysis brought to light the significant overlap between disease characteristic features and the mechanism of action of fluvastatin and olopatadine. The current study concludes the potentially beneficial use of fluvastatin in niche hepatitis C patient population suffering from nonalcoholic fatty liver diseases.


Assuntos
Antivirais/química , Biologia Computacional/métodos , Reposicionamento de Medicamentos/métodos , Fluvastatina/química , Hepacivirus/enzimologia , Cloridrato de Olopatadina/química , Proteínas não Estruturais Virais/química , Sítio Alostérico , Antivirais/uso terapêutico , Fluvastatina/metabolismo , Fluvastatina/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/genética , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Redes e Vias Metabólicas/genética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Cloridrato de Olopatadina/metabolismo , Cloridrato de Olopatadina/uso terapêutico , Ligação Proteica , Estrutura Secundária de Proteína , Transcriptoma , Interface Usuário-Computador , Proteínas não Estruturais Virais/antagonistas & inibidores
19.
Clin Microbiol Infect ; 30(3): 368-374, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38081413

RESUMO

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.


Assuntos
Aspergilose , COVID-19 , Coinfecção , Mucormicose , Humanos , Masculino , Mucormicose/complicações , Mucormicose/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Glucocorticoides , COVID-19/complicações , COVID-19/terapia , Fatores de Risco , Índia/epidemiologia , Hipóxia/complicações
20.
Lung India ; 40(5): 429-433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37787356

RESUMO

Background: Forced vital capacity (FVC) and six-minute walk distance (6MWD) are robust markers in interstitial lung diseases (ILD) to assess severity and prognosis. It is unknown whether high-resolution computed tomography pattern has any independent effect on the exercise capacity in ILD. We compared six-minute walk test (6MWT) parameters between usual interstitial pneumonia (UIP) and non-UIP ILD after adjusting for FVC. Methods: Data from a tertiary care ILD clinic were retrospectively analysed. Based on HRCT, patients were classified as UIP and non-UIP. 6MWT parameters and FVC were recorded for enrolled patients. 6MWD, distance-saturation product (DSP) and exertional desaturation were compared between UIP and non-UIP, using analysis of covariance (ANCOVA), with per cent predicted FVC as covariate. Patients were grouped as mild (≥70%), moderate (51%-69%) and severe (≤50%) based on FVC severity. Results: Out of 169 patients enrolled, only patients with all three data points: spirometry, 6MWT and HRCT were included in the analysis (n = 139). UIP group comprised 56 (40.3%), while non-UIP group had 83 (59.7%) patients. More females and lesser smokers were present in non-UIP group. Mean predicted FVC% was similar between the two HRCT groups (P = 0.611) and had a statistically significant, though very weak to weak correlation with 6MWT parameters {6MWD (r = 0.138); pred 6MWD% (r = 0.170); desaturation (r = -0.227); DSP index (r = 0.166)}. Analysis of covariance showed no statistically significant difference in the 6MWT parameters between UIP and non-UIP groups for similar FVC levels. Conclusion: For a similar level of lung function, exercise capacity was similar for patients with UIP and non-UIP pattern ILD.

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