Practice Guidelines for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis in an Intensive Care Setting.

Coronavirus disease-2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a new disease characterized by secondary Aspergillus mold infection in patients with COVID-19. It primarily affects patients with COVID-19 in critical state with acute respiratory distress syndrome, requiring intensive care and mechanical ventilation. CAPA has a higher mortality rate than COVID-19, posing a serious threat to affected individuals. COVID-19 is a potential risk factor for CAPA and has already claimed a massive death toll worldwide since its outbreak in December 2019. Its second wave is currently progressing towards a peak, while the third wave of this devastating pandemic is expected to follow. Therefore, an early and accurate diagnosis of CAPA is of utmost importance for effective clinical management of this highly fatal disease. However, there are no uniform criteria for diagnosing CAPA in an intensive care setting. Therefore, based on a review of existing information and our own experience, we have proposed new criteria in the form of practice guidelines for diagnosing CAPA, focusing on the points relevant for intensivists and pulmonary and critical care physicians. The main highlights of these guidelines include the role of CAPA-appropriate test specimens, clinical risk factors, computed tomography of the thorax, and non-culture-based indirect and direct mycological evidence for diagnosing CAPA in the intensive care unit. These guidelines classify the diagnosis of CAPA into suspected, possible, and probable categories to facilitate clinical decision-making. We hope that these practice guidelines will adequately address the diagnostic challenges of CAPA, providing an easy-to-use and practical algorithm to clinicians for rapid diagnosis and clinical management of the disease.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Diagnostic yield and safety of percutaneous CT-guided biopsy of retroperitoneal lesions and analysis of imaging features.

BACKGROUND: Computed tomography (CT)-guided biopsy is emerging as a preferred method for obtaining tissue samples from retroperitoneal lesions due to clear visualization of needle and vessels. PURPOSE: To assess diagnostic yield and safety of CT-guided biopsy of retroperitoneal lesions and compare CT findings in different disease categories. MATERIAL AND METHODS: This retrospective analytical study included 86 patients with retroperitoneal lesions who underwent CT-guided biopsy from December 2010 to March 2020. All procedures were performed with co-axial technique and multiple cores were obtained and subjected to histopathology. Additional tests like immunohistochemistry or microbiological analysis were done depending on clinical suspicion. Diagnostic yield calculation and comparison of imaging findings was done by one-way ANOVA, chi-square, and Fisher's exact tests. RESULTS: CT-guided biopsy was technically successful in all cases with a diagnostic yield of 91.9%. Minor complications in the form of small hematomas were seen in two patients. Major disease categories on final diagnosis were lymphoma, tuberculosis, and metastases. A variety of malignant and benign soft-tissue neoplasms were also noted less commonly. With help of immunohistochemistry, lymphoma subtype was established in 88.8% of cases. Addition of microbiological tests like the GeneXpert assay helped in the diagnosis of tuberculosis in some cases. A mass-like appearance and vascular encasement was common in metastatic group and lymphoma. CONCLUSION: Percutaneous CT-guided biopsy is a safe method for the sampling of retroperitoneal lesions with high diagnostic yield. Imaging findings are mostly overlapping; however, some features are more common in a particular disease condition.

Incorporating Lung Ultrasound in Clinical Pulmonary Infection Score as an Added Tool for Diagnosing Ventilator-associated Pneumonia: A Prospective Observational Study from a Tertiary Care Center.

Background: Clinical pulmonary infection score (CPIS) is an established diagnostic parameter for ventilator-associated pneumonia (VAP). Lung ultrasound (LUS) is an evolving tool for diagnosing VAP. Various scores have been proposed for the diagnosis of VAP, taking LUS as a parameter. We proposed whether replacing LUS with chest radiograph in CPIS criteria will add to the diagnosis of VAP. The current study was done to evaluate the diagnostic accuracy of LUS alone and in combination with clinical and microbiological criteria for VAP by replacing chest radiograph with LUS in CPIS. Materials and methods: We conducted a prospective single-center observational study including 110 patients with suspected VAP to investigate the diagnostic accuracy of LUS. Quantitative mini-bronchoalveolar lavage (mini-BAL) culture was considered the gold standard for diagnosis of VAP. Here, the authors have explored the combination of LUS, clinical, and microbiology parameters for diagnosing VAP. On replacing chest radiograph with LUS, sono-pulmonary infection score (SPIS) and modified SPIS (SPIS-mic, SPIS-cult) was formulated as a substitute for CPIS. Results: Overall LUS performance for VAP diagnosis was good with sensitivity, specificity, positive or negative predictive value, and positive or negative likelihood ratios of 91.3%, 70%, 89%, 75%, 3, and 0.1, respectively. Adding microbiology culture to LUS increased diagnostic accuracy. The areas under the curve for SPIS and modified SPIS were 0.808, 0.815, and 0.913, respectively. Conclusion: The diagnosis of VAP requires agreement between clinical, microbiological, and radiological criteria. Replacing chest radiograph with LUS in CPIS criteria (SPIS) increases diagnostic accuracy for VAP. Adding clinical and culture data to SPIS provided the highest diagnostic accuracy. Clinical parameters along with lung ultrasound increase diagnostic accuracy for VAP. How to cite this article: Samanta S, Patnaik R, Azim A, Gurjar M, Baronia AK, Poddar B, et al. Incorporating Lung Ultrasound in Clinical Pulmonary Infection Score as an Added Tool for Diagnosing Ventilator-associated Pneumonia: A Prospective Observational Study from a Tertiary Care Center. Indian J Crit Care Med 2021;25(3):284-291.

Case 249: Intramuscular Mycetoma.

History A 21-year-old man presented with swelling of the medial aspect of the left thigh of 1-month duration. There was no history of fever or penetrating injury in the left thigh. The patient had undergone renal transplantation 7 years earlier and had been taking immunosuppressants since transplantation. He had undergone two surgeries at the same site in the medial aspect of the left thigh in the past 3 years for a similar problem. At physical examination, there was swelling in the medial aspect of the left thigh, with mild tenderness. A surgical scar was noted anterior to the swelling ( Fig 1 ). No redness or discharging sinus was present. Laboratory results were as follows: hemoglobin level, 11.3 g/dL (normal range, 13.8-17.2 g/dL); white blood cell count, 9.7 × 109/L (normal range, [4-11] × 109/L); neutrophil, 75% (normal range, 48%-77%); lymphocyte, 22% (normal range, 10%-24%); eosinophil, 1% (normal range, 0.3%- 7%); monocyte, 1% (normal range, 0.6%-10%); serum creatinine level, 1.3 mg/dL (114.9 µmol/L) (normal range, 0.5-1.6 mg/dL [44.2-141.4 µmol/L]); and serum glucose (random) level, 82 mg/dL (4.5 mmol/L) (normal range, 79-140 mg/dL [4.4-7.8 mmol/L]). Radiography of the left thigh showed soft-tissue swelling in the medial aspect of the left thigh, without underlying bone involvement (not shown). Ultrasonography (US) and magnetic resonance (MR) imaging of the left thigh were performed. [Figure: see text].

Posterior reversible encephalopathy syndrome following blood transfusion in a patient with factor X deficiency: Is it an unusual systemic manifestation of an adverse transfusion reaction?

Adverse neurological transfusion reactions including posterior reversible encephalopathy syndrome (PRES) following blood transfusion are rare. Our case an 18-year-female with known Factor X deficiency with menorrhagia developed severe hypertension, followed by generalised tonic clonic convulsions apparently after blood component transfusion. She had earlier received 4 units of red blood cells (RBC) for anaemia and 10 units of fresh frozen plasma (FFP) for menorrhagia (with prolonged PT and APTT) within short span of time at another hospital. There was no history of hypertension, convulsions, any cardiovascular, renal or neurological disease before transfusion. The clinical features and magnetic resonance imaging findings led to the diagnosis of PRES. Abnormal electroencephalogram and a hypercoagulable haemostatic profile on thromboelastography along with derangement in blood glucose and liver function tests were also observed. Patient responded well to the anticonvulsants and antihypertensive agents prescribed and was discharged in a stable condition. Our patient had a systemic transfusion reaction involving predominantly neurological system, however, cardiovascular, hepatic, haemostatic and endocrine systems were also affected. This case is unusual being the first report of PRES occurring in a patient with factor X deficiency presenting with an array of clinical and laboratory features which have not been reported in earlier studies involving PRES. Presumably the initial aggressive red cell transfusion to treat anaemia initiated the crisis and further large volumes of transfused FFP contributed to this adverse transfusion reaction in our case. Clinicians and Transfusion Medicine specialists should be aware about this uncommon clinical entity.

Is multiple session of intralesional bleomycin mandatory for complete resolution of macrocystic lymphatic malformation?

BACKGROUND: Intralesional bleomycin scelro-therapy has become a favored line of treatment for macrocystic lymphatic malformations. However the need for multiple sessions is a drawback associated with this treatment modality. Our aim is to document whether multiple session of intra- lesional sclero-therapy is necessary for complete resolution of cystic lymphatic malformation. METHOD: Intralesional bleomycin under Ultrasound guidance was used for macrocystic lymphangioma at concentration of 3mg/ml but not exceeding the total dose (1mg/kg) body weight for single session or cumulative dose of 5mg/kg. In all cases intralesional sclerosant (ILS) was installed under proper aseptic precaution in operation theatre in general anesthesia or sedation depending on the site or size of lesion and age of the patient. Age of patients at the time of enrolment in study ranged from 3 months to 18 years. Clinical examination was the main stay of diagnosis which was supplemented by USG and/or computed tomography. Compression of the lesion site was done for few hours wherever it was possible after the ILS session. RESULT: A total of 21 patients included in our study. The age ranged from 3 months to 18 years. Male to female ratio was 8:13. The most common site of involvement was neck and axilla followed by anterior chest wall and nape of the neck. Complete resolution after single session was observed in 90.5% cases where as surgery was required in 9.5% case. Major complication was observed in one patient, who had intralesional bleeding which was managed conservatively. Transient pain and fever was observed in 23.8% of cases. Only two patient required surgical intervention where one had persistent subcutaneous fibrotic nodule and other one did not respond to ILS. CONCLUSION: Intralesional bleomycin is an effective treatment for macrocystic lesion, and complete resolution may be achieved by single session of ILS if proper principle are followed.

Three-dimensional visualization of intracranial tumors with cortical surface and vasculature from routine MR sequences.

The simultaneous three-dimensional (3D) visualization of intracranial tumors, brain structures, skull, and vessels is desired by neurosurgeons to create a clear mental picture of the anatomical orientation of the surgical field prior to the surgical intervention. Different anatomical and pathological components are usually visualized separately on different magnetic resonance (MR) sequences; however, during surgery, they are tackled simultaneously. Another problem is that most present day MR workstations enable review of two-dimensional (2D) slices only with limited postprocessing options. With recent software developments, a simultaneous 3D visualization simulating the real surgical field is possible using commercial or open source softwares. The authors have reviewed the important concepts and described a technique of interactive 3D visualization from routine 3D T1-weighted, MR angiography, and MR venography sequences using open source FSL (Functional MRI of the brain software library) and BrainSuite softwares.

Biophysical modeling and diffusion kurtosis imaging reveal microstructural alterations in normal-appearing white-matter regions of the brain in obstructive sleep apnea.

Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. Results: OSA was diagnosed when the patient's apnea-hypopnea index was ≥ 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.

A rare case of isoniazid mono-resistant tuberculosis presenting as cardiac tamponade along with an anterior mediastinal mass in a 15-year-old immunocompetent patient.

ABSTRACT: A 15-year-old boy presented with a sudden onset of breathlessness for 7 days, gradual loss of weight of 17.6 lbs over the last month and progressive hoarseness of voice for 7 months. The contrast-enhanced computed tomography (CECT) scan revealed a heterogeneously enhancing lesion in the anterior mediastinum with multiple discrete lymph nodes in the cervical and mediastinal locations. The GeneXpert MTB/RIF assay performed on the CT-guided biopsy of the mass was negative, but the culture for Mycobacterium tuberculosis was positive at 7 weeks of incubation. There was a suboptimal radiological response after 6 months of treatment. First-line drug susceptibility testing (DST) performed by line probe assay (LPA) on the positive culture detected high-level resistance to isoniazid. The treatment was modified as per DST results to which the patient responded well.

Role of percutaneous CT-guided biopsy in the characterisation of pleural diseases.

Background: Computed tomography (CT)-guided biopsy is emerging as a preferred and safe method for obtaining tissue samples in pleural diseases. Objective: This study aimed to evaluate the diagnostic yield and safety of percutaneous CT-guided biopsy in pleural diseases and to find CT findings predictive of malignant neoplastic pleural disease. Material and Methods: This retrospective study included 77 patients with pleural disease who underwent CT-guided pleural biopsies from July 2013 to May 2020. All procedures were performed with a coaxial semi-automatic biopsy device. Histopathology was performed in all cases, and additional tests such as immunohistochemistry (IHC) or microbiological analysis were carried out depending on clinical suspicion. The correlation of CT findings with final diagnosis was performed by Chi-square, Fisher's exact test and logistic regression analysis. Results: The overall technical success rate of CT-guided pleural biopsy was 100% with a diagnostic yield of 96.1%. No major complication was encountered, with minor complications encountered in the form of minimal pneumothorax and chest pain. Malignant pleural conditions constituted the largest group including metastatic adenocarcinoma as the most common (31.2%), followed by metastatic squamous cell carcinoma and mesothelioma. Tubercular pleural involvement was the second most common category (16.9%). The cartridge-based nucleic acid amplification test (CB-NAAT) assay had 90% sensitivity on pleural tissue in tubercular cases. CT features predictive of malignancy were irregular and nodular pleural thickening, mediastinal and diaphragmatic pleural involvement and mediastinal/chest wall invasion. There was a good correlation between higher pleural thicknesses with malignant outcome. Conclusion: Percutaneous CT-guided biopsy is a safe method for obtaining pleural tissue samples with high diagnostic yield. CT findings provide clues, which favour malignant pleural involvement.

Role of circulating microRNAs in non-small cell lung carcinoma.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the leading cause of mortality globally. Early imaging detection modalities are associated with high false-positive rates and radiation exposure. A non-invasive biomarker can serve as an improvised method for early detection. MicroRNAs can serve as a potential non-invasive biomarker as they are stable in circulation, tissue or biological process-specific, easy to detect, cost-effective, and not associated with radiation hazards. This study validates circulating microRNA in NSCLC of the Indian population and studies its correlation with clinicopathological parameters. MATERIALS AND METHODS: Circulating microRNA (-miR-193b, miR-301a, miR-7, and miR-25) was evaluated in 101 cases of tissue-proven NSCLC and 28 controls in serum samples. RESULTS: There were 67 male and 34 female patients (Male: Female = 1.97:1). The age range was 25 to 86 years with a median age of 60 years. There was a significant upregulation in the expression of miR-193b in the NSCLC group as compared to controls (P = 0.034). MiR-7 was also upregulated while miR-25 and miR-301a were downregulated in NSCLC as compared to controls; however, a level of significance was not achieved. ROC curve analysis for miR-193b showed an AUC of 0.636 (95% CI, 0.522-0.750; P-value = 0.036) between NSCLC cases and controls. CONCLUSION: The present study showed variable expression of the above-studied miRNAs. MiR-193b showed a significant upregulation in cancer patients; however, the other three miRNAs were not conclusive. This suggests that profiling of microRNA in each population is essential to search for a valid non-invasive biomarker in that population.

Nonsurgical hypoparathyroidism is associated with skeletal muscle dysfunction and restrictive lung disease.

CONTEXT: Systematic assessment of skeletal muscle function is lacking in patients with nonsurgical hypoparathyroidism (HP). Whether muscle dysfunction involves respiratory muscles and results in restrictive lung disease (RLD) is not studied. OBJECTIVE: To assess skeletal muscle and pulmonary functions in patients with HP. DESIGN: Observational case-control study. METHODS: Thirty patients with HP (mean age 37.7 years, 60% males) and 40 age-, sex-, and body mass index (BMI)-matched healthy controls were assessed for skeletal muscle function by handgrip strength, the short physical performance battery (SPPB) test, dual-energy X-ray absorptiometry (DXA), and electromyography (EMG). Pulmonary function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide, and diaphragmatic ultrasound (DUS). RESULTS: Patients with HP had lower serum calcium (2.25 ± 0.15 vs 2.4 ± 0.12 mmol/L, P < .001), serum magnesium (median [interquartile range] 0.74 [0.69-0.82] vs 0.78 [0.69-0.90] mmol/L, P = .04), handgrip strength (18.08 ± 8.36 vs 22.90 ± 7.77 kg, P = .01), and composite SPPB scores (9.5 [7-10] vs 12 [12-12], P < .001) compared to healthy controls. Electromyographic evidence of myopathy was seen in 23% (5 of 22) of patients with HP but in none of the controls (P = .08). The prevalence of RLD was higher in the HP cohort compared to that in controls (24% vs 0%, P = .01). Diaphragmatic excursion (DE) (4.22 ± 1.38 vs 5.18 ± 1.53 cm, P = .01) and diaphragmatic thickness (DT) (3.79 ± 1.18 vs 4.28 ± 0.94 mm, P = .05) on deep inspiration were reduced in patients with HP. CONCLUSION: Detailed testing of patients with HP without overt muscle and lung diseases revealed significant impairment in parameters of skeletal muscle function. Myopathy and RLD were observed in a considerable proportion of patients with HP.

Thrombosis leading to acute abdomen in corona virus disease- 19:A case series.

Involvement of the gastrointestinal (GI) system in corona virus disease-19 (COVID-19) in form of diarrhea, loss of taste, nausea, and anorexia is common and associated with poor prognosis. COVID-19 is also associated with a hypercoagulable state that mainly involves the pulmonary vasculature. However, GI complications involving thrombosis are observed infrequently. We report two COVID-19 patients who had two different causes of acute abdomen. The first patient was a 49-year-old male diagnosed with an aortic thrombus along with a splenic infarct. He was diagnosed early and successfully managed with anticoagulants. The second patient was a 30-year-old male who developed pain in the abdomen and was found to have features suggestive of peritonitis. A contrast-enhanced computerized tomography (CECT) scan of the abdomen revealed dilated bowel loops. Immediate exploratory laparotomy was performed; he was found to have jejunal perforation with gangrene. Histopathological examination of the resected specimen showed inflammatory cells with edema and thrombotic vessels. However, he succumbed to sepsis and multiorgan failure. Therefore, it is important to investigate cases of acute abdomen in COVID-19 thoroughly and whenever indicated CT angiogram should be obtained.

Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly.

BACKGROUND: Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly. DESIGN: Prospective, observational. MATERIALS AND METHODS: Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls. RESULTS: Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration. CONCLUSION: Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly.