Comparison of direct versus concentrated smear microscopy in detection of pulmonary tuberculosis

Mohammad Khaja
Mafij Uddin
MdRaihan Chowdhury
Shahriar Ahmed
MdToufiq Rahman
Razia Khatun
Frank Van Leth
Sayera Banu
Comparison of direct versus concentrated smear microscopy in detection of pulmonary tuberculosis
R E S E A R C H A R T I C L E Open Access
Background: Sputum smear microscopy is fast and inexpensive technique for detecting tuberculosis (TB) in high incidence areas but has low sensitivity. Physical and chemical sputum processing along with centrifugation have been found to show promise in overcoming this limitation. Our objective was to compare the sensitivity of smear microscopy obtained with smears made directly from respiratory specimens to those from concentrated specimens.Methods: By active screening, 915 TB suspects were identified from Dhaka Central Jail and sputum specimens were aseptically collected. Direct smears were prepared by taking a small portion of the purulent part of the sputum with a sterile loop. The specimens were then processed by a standard N-acetyl-L-cysteine-NaOH digestion-decontamination method to prepare concentrated specimens. Both smears were then air dried, heat fixed, and stained by the Ziehl-Neelsen staining technique. The stained slides were examined under oil immersion and were graded following International Union Against Tuberculosis and Lung Diseases guidelines. All the specimens were inoculated into Lowenstein-Jensen (L-J) media and culture results were considered as gold standard to calculate sensitivity. Results: Of 915 specimens, 73 (8%) specimens were positive both on direct and concentrated methods, one sample was positive on direct microscopy but was negative on concentrated method. An extra 14 (1.5%) samples were positive on concentrated method which were negative on direct smear. In L-J media 105 specimens were found positive for TB bacilli and of them, 74 (70.5%) and 87 (82.9%) were positive in direct and concentrated smear, respectively. The sensitivity of direct and concentrated smear microscopy was different when using positive culture as the gold standard (71% vs. 83%).Conclusions:The results showed that concentrated technique increases the sensitivity of microscopy up to 12%. Therefore, the national programs in high TB burden countries may consider incorporating the technique into their guidelines at least in the district and higher level laboratories to improve case finding strategy.

Background

Tuberculosis (TB) continues to be a major public health threat worldwide despite the availability of many highly sensitive diagnostic tools and highly efficacious treatment for decades. It is more of a threat in the developing world. There were an estimated 8.8 million new cases (incidence) of TB (range, 8.5 million-9.2 million) globally in 2010, 1.1 million deaths (range, 0.9 million-1.2 million) among human immunodeficiency virus (HIV)negative cases of TB and an additional 0.35 million deaths (range, 0.32 million-0.39 million) among people who were HIV-positive. This makes TB the second leading cause of death among the infectious diseases [1]. A staggering 95% of these cases and deaths occur in the developing countries [2,3].

Early diagnosis of TB is crucial both clinically and epidemiologically. It is essential to ensure proper and early identification of cases, and good treatment outcomes to be able to limit its transmission and obtain successful TB control [4]. The gold standard for pulmonary TB diagnosis is culture of sputum in liquid media. However, due to lack of access to culture facilities and the long turn-around times involved with sputum culture, most programmes use direct Ziehl-Neelsen (Z-N) microscopy for detection of acid-fast bacilli (AFB) in sputum smears as their main diagnostic tool. In this method, the sputum specimens are smeared directly on to the slides without any processing and subjected to ZN staining. AFB microscopy is believed to be the most practical and fastest technique in establishing a diagnosis of pulmonary TB, especially in developing countries where most of the TB cases live [4,5]. Studies have shown that direct smear microscopy is highly specific in settings where TB is more prevalent [6,7]. Though AFB microscopy is simple, inexpensive and provides rapid result, it has some limitations. The threshold for detection of AFB in sputum samples under optimal conditions is between 10 4 and 10 5 bacilli per ml. The sensitivity and specificity of AFB microscopy is low when compared to culture method. In some studies it has been shown that this technique has a low sensitivity, 22-43% for a single smear [8] and up to 60% under optimal conditions [9,10] when compared with that of cultures. Sensitivity is even more reduced if samples are of poor quality, which is often the case in children and HIV-coinfected patients [11,12]. Although all mycobacterial species are acid fast, this assay is highly specific for M. tuberculosis in countries where TB is endemic [13].

Microscopy clearly has many advantages when it comes to speed and feasibility, and if sensitivity could be improved it has the potential to become an even more valuable tool for National TB Control Programmes (NTPs) around the world. In the last decade many researchers have suggested that the performance of sputum smear microscopy can be significantly improved if sputum is liquefied with chemical reagents and then concentrated by centrifugation or sedimentation prior to acid-fast staining [14,15]. Out of them, the technique using N-acetyl-L-cysteine (NALC) with 2% sodium hydroxide (NaOH) is considered to be the best. NALC acts as a strong mucus digester and the smear processed by it has less debris and a greater concentration of AFB [16]. This method has been found to increase the sensitivity of microscopy substantially [10]. However, it requires some level of staff training, increases time needed for diagnosis, and requires some level of biosafety arrangement to ensure the security of the lab personnel. Due to resource constraints, it is not applied in the majority of TB laboratories in developing countries [17,18].

Another chemical, sodium hypochlorite, usually known as household bleach is considered as an ideal chemical processing agent for use in low income countries. It is widely available and inexpensive, and its disinfectant properties could improve infection control in laboratories lacking biosafety facilities. It is reported that bleach increase the sensitivity of smear microscopy through the digestion of mucus and debris in sputum and resulting in clearer microscopy field [19]. One of the notable disadvantages of bleach sedimentation is that a bleach treated sample cannot be used for mycobacterial culture, as the bleach kills M. tuberculosis.

Another recent development in smear microscopy is the advent of fluorescence microscopy (FM). Examination of sputum smears stained with Z-N requires on an average 5-10 minutes, consuming considerable working hours from the laboratories with limited resources. The newer alternative technique to Z-N smear microscopy, FM is known to increase the sensitivity (10% higher) when compared with Z-N microscopy methods while speeding up the whole process to consume much lesser time [20]. Fluorescent AFB can be seen at lower magnification than Z-N stained AFB. FM smears can be examined in a fraction (about 25%) of the time needed for Z-N smears as well. Recent development of simple FM systems based on light-emitting diodes (LED-FM) which have long lifespans, do not produce UV light, and have minimal power requirements could facilitate the implementation of FM in high burden and limited resources countries [21].

The use of sputum smear as a screening procedure for the diagnosis of pulmonary TB has recently been criticized following the finding by several large laboratories that up to 55% of specimens with positive smear failed to grow in culture while 30% are smear negative but culture positive [22,23]. The use of different smearing techniques varies from one laboratory to another. In most of the low and middle income countries the direct smear technique is used and only a few uses the concentrated method [23]. Though the resource needed to practice concentrated smearing technique remains a problem in many laboratories, it has been shown that concentration and liquefaction improve the sensitivity of the AFB smear microscopy and can contribute significantly to achieve better accuracy of diagnosis [24].

As microscopy is the mainstay of TB diagnosis in our country, in this study we wanted to compare the sensitivity obtained with smears for detection of AFB prepared directly from respiratory specimens (direct AFB smears) to that obtained with the parallel smears prepared from concentrate of the specimens (concentrated AFB smears) in our country context. This information may be of great help to the NTP in formulating effective TB control guidelines.

Methods

Specimen processing and culture

A total of 915 sputum specimens were aseptically collected from prisoners of the Dhaka Central Jail who were suspected to have pulmonary TB disease on the basis of their presenting symptoms. A suspect was defined as an individual if he/she had persistent cough for more than three weeks, and/or evening rise of temperature for more than two weeks, and/or body mass index (BMI) less than 16. A brief study questionnaire was used to identify the suspects among the inmates in Dhaka Central Jail, the largest prison in Bangladesh. The collected specimens were transported in specimen transportation box (cool box) to the Tuberculosis Laboratory at International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) for AFB microscopy and culture.

Specimens were scored as saliva or sputum on the basis of visual examination. Suspects were requested to give another specimen in case of saliva specimens. This approach has been assessed as being feasible for the detection of specimens with a high probability of being positive a culture in a clinical setting. The use if this approach in a population-based screening programme outside the clinical setting is not to be recommended [25]. Direct smears were prepared by taking a small portion of the purulent part of the sputum with a sterile loop. The specimens were then processed by a standard NALC-NaOH digestion-decontamination method; briefly, an equal volume of 2% NaOH and 1.45% sodium citrate containing 0.5% NALC were added to each tube. The contents within the tubes were then mixed by vortexing and then incubated at room temperature for 15 minutes. The tubes were then shaken by hand at regular intervals. Phosphate-buffered saline (pH 6.8) were added up to 45 ml and then centrifuged at 3000X g for 15 minutes. The supernatant were carefully poured off, the resulting sediments were then resuspended in 1.5 ml of phosphate-buffered saline, and the suspensions were used to prepare smear (concentrated smear) and to inoculate into Lowenstein-Jensen (L-J) culture media. Though the World Health Organization (WHO) recommended gold standard in TB diagnosis is culture of sputum in liquid media, in our study we have used culture in solid media (L-J) as gold standard as no liquid culture facility was available in our country during the study period.

AFB smear and microscopy

Smears made from original specimens and/or from the concentrated specimens were air dried, heat fixed, and stained by the ZN staining technique. The stained slides were examined under oil immersion (1,000x lens objective), and they were reported negative when no AFB were seen in at least 100 microscopic fields. Smears were graded positive [17] for any of the following observations: when 1 to 9 AFB were seen in 100 microscopic fields (scored as scanty positive), when 10 to 99 AFB were seen in 100 fields (scored as 1+), when 1 to 10 AFB were seen per field in at least 50 fields (scored as 2+), and when more than 10 AFB were seen per field in at least 20 fields (scored as 3+). Direct smear and concentrated smears were examined separately by two laboratory technicians without knowing the results of each other. A total of 10% slides from both methods were reexamined by the laboratory supervisor and his classification was final in case of discrepancies.

All the specimens inoculated into L-J media were incubated at 37°C for 6 to 8 weeks in a vertical position for the better development of individual colonies. When small and buff colored colonies grew on LJ medium, the sample was considered as positive. Contaminated cultures (e.g. growth of moulds, and also those in which the medium had liquefied or turned dark green) were discarded.

The study protocol was approved by the Ethical Review Committee of International Centre for Dirrhoeal Disease Research, Bangladesh (icddr,b). All study subjects were enrolled in the study only after they had provided informed written consent.

Data entry and analysis

All calculations were performed using SPSS, version 17.0 for Windows. Sensitivity and specificity were calculated for each diagnostic technique and expressed as percentages at 95% confidence intervals. The McNemar test was used to compare the sensitivity of the different tests.

Results

Out of 915 specimens 74 (8.1%) were found to be AFB positive and 841 (91.9%) were found AFB negative by direct AFB smear. Among the positive specimens, 9 (1%) were scanty positive, 19 (2%) were 1+, 27 (3%) were 2+ and 19 (2%) were 3+. In contrast, 87 (9.5%) were found to be AFB positive and 828 (90.5%) were AFB negative when smear prepared from the concentrated specimens. Among the positive specimens 13 (2%), 18 (2%), 26 (3%), 30 (3%) were scanty positive, 1+, 2+ and 3+ respectively ( Table 1).

Grading of AFB between the slides prepared from the same sample using direct and concentrated method was compared. Of the 915 specimens, 73 (8%) specimens were positive both on direct and concentrated methods, one sample was positive on direct microscopy but was negative on concentrated method. An extra 14 (1.5%) samples were positive on concentrated method which were negative on direct smear. More than 90% of the samples were found to be negative on both methods. Among 841 negative specimens on direct microscopy, 11 (1.3%) and 3 (0.4%) were found to be positive on concentrated methods. More than 66% of scanty, 52.6% of 1+ and 37.1% of 2+ AFB on direct microscopy were converted into 1+, 2+ and 3+ respectively on concentrated smear microscopy. No difference was found in case of high positive (3+) on both methods (Table 1). Among the 915 specimens, 105 (11.5%) were found to be positive on culture. Considering 105 culture positive cases, 74 (70.5%) and 87 (82.9%) of them were AFB positive in direct and concentrated smear, respectively ( Table 2). About 17.1% culture positive cases were found to be negative on both direct and concentrated AFB microscopy.

The sensitivity of direct and concentrated smear microscopy was different when using positive culture result as the gold standard. Applying the McNemar χ 2 test, the difference between sensitivities (71% versus 83%; p = 0.002) obtained by the two methods was found to be significant. These results showed that concentrated technique increases the sensitivity of microscopy up to 12% when performed with the same specimens. Among the 810 patients with negative cultures, the specificity (100%) was similar for both techniques.

Discussion

This study showed that the use of the concentrated method for preparing smears for AFB microscopy increases sensitivity without a loss of specificity in identifying positive TB cases, compared to the direct method.

The specimen that was positive with the direct method but negative with the concentrated method was also found to be positive by culture. It was an uncommon phenomenon and theoretically it is difficult to explain such cases. It might have occurred due to inappropriate sample concentration and smear preparation, smear preparation from a negative sample accidentally, faulty staining process, or inappropriate microscopic observation.

Eight specimens were found to be positive in both direct and concentrated smear microscopy but negative in culture. From the clinical data, it was observed that these patients were taking anti-TB drugs while collecting the specimens. During treatment, only the dead/killed bacteria remain in the respiratory specimen (sputum) which were detected by microscopy but were unable to grow in L-J media.

A study conducted by Barez, et al. [26] showed that the sensitivity was almost similar in both methods as described 81.6% for direct method and 82.7% for the concentrated method. In another study, Cattamanchi et al. [27] failed to find a difference in sensitivity between direct and concentrated sputum smear microscopy, the calculated sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%). In a similar study conducted by Peterson et al. [28] in two different laboratory settings (a tertiary-care laboratory and several local outpatients clinics) found that in a tertiary-care hospital the direct smear was significantly less sensitive than the concentrated smear (28% and 51%, respectively) and in the samples from outpatients of the Pacific islands the direct smear was less sensitive than that made from the concentrated specimen (82 versus 93%, respectively).

Despite some evidence that the concentrated method can be superior to the direct method, it is not being performed in peripheral TB laboratories in low-income countries, because of the following concerns: feasibility of centrifugation in settings with irregular power supply; limited human and financial resources; inadequate training capacity; lack of proper biosafety arrangements; and potential biohazard posed by centrifugation. In most resource poor countries like Bangladesh where TB is endemic, most of the microscopy centers are using direct smear microscopy with low sensitivity for the diagnosis of TB. However, in the light of our study findings, it may be recommend that concentrated smear microscopy can be used in place of conventional direct microscopy where appropriate facility is available, to achieve better diagnostic accuracy and ensure greater success of the TB control programmes. It may not be recommended as an ideal alternative to existing conventional microscopy considering the cost implications and other resource constraints involved with its implementation in the wide network of Bangladesh NTP, and other high TB burden countries. As alternative approaches like recently developed LED-FM microscopy and low cost sedimentation technique have shown to increase the sensitivity of microscopy without the involvement of much of resource, these can be considered to be incorporated in the national TB control activity framework rather than concentrated smear technique. However, for the district level laboratories where minimum biosafety arrangements can be made by putting in low cost biosafety cabinets and other constraints can be overcome, this concentrated smearing technique can be practiced to ensure better case detection of TB. There is still scope of further research to compare the outputs of concentrated smear technique and LED-FM in settings where appropriate resources are available. Research may also be conducted to find out the benefit of combining concentrated sample and fluorescent staining technique. As both these methods are already documented to increase the sensitivity of smear microscopy, their combination may have incremental effect and have the potential to increase the sensitivity of microscopy significantly.

Conclusion

The study showed that concentrated AFB microscopy is more efficient to detect M. tuberculosis in respiratory specimens than direct AFB microscopy. Due to resource constraints it may not be suitable for implementing in the wide network of NTP microscopy centers thorough out the country but it may be considered for the district and other higher level TB diagnosis centers which have more resources available at their disposal to ensure greater success in TB case detection.

Table 1
1Comparison of quantization of AFB from direct and concentrated smear microscopyDirect
smear
results

No. of specimens with the following
concentrated smear results:

Total

Negative
n (%)

Scanty
n (%)

1 +
n (%)

2 +
n (%)

3 +
n (%)

Negative 827 (98.3) 11 (1.3) 3 (0.4)
841

Scanty
1 (11.1)
2 (22.2) 6 (66.7)
9

1+
8 (42.1) 10 (52.6) 1 (5.3)
19

2+
1 (3.7)
16 (59.3) 10 (37.0) 27

3+
19 (100) 19

Total
828
13
18
26
30
915

Table 2
2Comparison of both microscopy methods with the gold standard culture methodAFB microscopy
Gold standard +
Gold standard -
Total
Sensitivity % (95% CI)
Specificity % (95% CI)

Direct
+
74
0
74
70.5 (60.8 -79.0)
100 (99.5 -100)
-
31
810
841

Concentration
+
87
0
87
82.9 (73.2 -88.7)
100 (99.5 -100)
-
18
810
828

Total
105
810
915

http://www.biomedcentral.com/1756-0500/6/291
AcknowledgementsWe are thankful to the Directorate of Prisons who helped us in performing this study in this difficult setting. We also thank all the doctors and support staff of Dhaka Central Jail Hospital for their help and support. Our sincere gratitude goes to all the prison inmates who participated in this study to make it a success.Competing interestsThe authors declare that no competing interests exist.Authors' contributions
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Fulminant Myocarditis Following SARS-CoV-2 Infection JACC Patient Care Pathways

MDSaurabh Rajpal
MDRami Kahwash
DOMatthew S Tong
DOKelly Paschke
MDAnjali A Satoskar
Department of Pathology
The Ohio State University Wexner Medical CenterColumbusOhioUSA

MDBeth Foreman
MD, MHSLarry A Allen
Division of Cardiology
Department of Medicine
School of Medicine
University of Colorado
AuroraColoradoUSA

MDNicole M Bhave
Division of Cardiology
Department of Internal Medicine
School of Medicine
University of Michigan
Ann ArborMichiganUSA

MD, MHATy J Gluckman
Center for Cardio-vascular Analytics, Research, and Data Science (CARDS)
Providence Heart Institute, Providence St. Joseph HealthPortlandOregonUSA

MDValentin Fuster

JACC PATIENT CARE PATHWAYS
Division of Cardiology
Department of Internal Medicine
The Ohio State University Wexner Medical CenterColumbusOhioUSA

Fulminant Myocarditis Following SARS-CoV-2 Infection JACC Patient Care Pathways
10.1016/j.jaccas.2022.03.013; f The Zena and Michael Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; and the g Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Muthiah Vaduganathan, MD, MPH, served as Guest Associate Editor for this paper. Javed Butler, MD, MPH, MBA, served as Guest Editor-in-Chief for this paper. This paper is co-published in the Journal of the American College of Cardiology. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center. Manuscript received March 21, 2022; accepted March 22, 2022. J A C C : C A S E R E P O R T S V O L . 4 , N O . 1 0 , 2 0 2 2 ª 2 0 2 2 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N P U B L I S H E D B Y E L S E V I E R
A 60-year-old woman with a past medical history of asthma presented with fulminant myocarditis 9 days after testing positive for SARS-CoV-2 and 16 days after developing symptoms consistent with COVID-19. Her hospital course was complicated by the need for veno-arterial extracorporeal membrane oxygenation, ventricular arrhythmias, and pseudomonas bacteremia. She ultimately recovered and was discharged to home with normal left ventricular systolic function. Thereafter, she developed symptomatic ventricular tachycardia, for which she received an implantable cardioverter-defibrillator and antiarrhythmic drug therapy. (J Am Coll Cardiol Case Rep 2022;4:567-575) © 2022 by the American College of Cardiology Foundation.CASE PRESENTATIONA 60-year-old woman with a past medical history of asthma presented to the emergency department (ED) during the summer of 2020 with extreme fatigue, shortness of breath, and palpitations.Nine days prior, she was seen by her primary care physician to evaluate a week of symptoms, including fever, decreased sense of smell and taste, body aches, sore throat, and congestion. These symptoms began several days after close contact with someone who was COVID-19 positive. She was diagnosed with SARS-CoV-2 infection by a PCR test and was started on supportive treatment with antipyretics. Although her symptoms improved initially, she came to the ED because of worsening fatigue, shortness of breath, and a heart rate of approximately 140 beats/min on a home monitor. Initial vital signs included a heart rate of 141 beats/ min, blood pressure of 138/63 mm Hg, temperature of 97.3 F, respiratory rate of 16 breaths/min, and oxygen saturation by pulse oximetry of 98% on room air. Upon arrival, she was not in respiratory distress, her
 Table 1)
. Cardiology consultation was requested.

Out of concern for an acute coronary syndrome, she was treated with aspirin, intravenous heparin, intravenous nitroglycerin, metoprolol, and atorvas-  Echocardiography and coronary angiography to exclude obstructive coronary artery disease are usually part of the initial evaluation of patients with suspected myocarditis. Echocardiographic features of myocarditis include ventricular wall motion abnormalities often in a noncoronary distribution, increased left ventricular wall thickness, abnormal ventricular strain, and reduced left ventricular systolic function.

CMR is the preferred noninvasive test for evaluation of myocarditis and can also be used as a supplemental strategy for ongoing assessment and risk stratification. Persistence of LGE is an independent risk factor for mortality, heart failure, need for heart transplantation, and arrhythmias including sudden cardiac death.

EMB is considered the gold standard for diagnosis of myocarditis, and despite its low yield, can be useful in confirming the diagnosis and evaluating for specific etiologies, like giant cell or eosinophilic myocarditis, that may require specific therapies.

Arrhythmias represent important shortand long-term risks with myocarditis. Over the next few days, her inotropic support was weaned off. On ECMO day 9, flow was weaned to 1.3 L/min, without worsening oxygenation, and a bedside echocardiogram demonstrated severely reduced but improving left ventricular systolic function with an ejection fraction of 25%-30%. On ECMO day 10, she was taken to the operating room, ECMO was weaned, and she was decannulated     In all cases of myocarditis, exclusion of obstructive coronary artery disease is important, most often with invasive coronary angiography. This is particularly important in the setting of COVID-19, in which ischemic heart disease may be found at a higher rate. 8 CMR can be used to confirm myocarditis and is the preferred noninvasive test for its evaluation. 3, [9][10][11] However, in fulminant cases, patient instability may prohibit its use, at least initially. Updated Lake Louise Criteria, which incorporate T 1 abnormalities (elevated native T 1 and/or late gadolinium enhancement [LGE]) and elevated native T 2 signals (in a focal or global distribution representative of myocardial edema or inflammation), along with additional supportive criteria (eg, regional or global dysfunction, pericardial effusion) (Figure 3), are highly sensitive and specific for those with suspected myocarditis. 12,13 T 1 and T 2 mapping improves diagnostic yield with CMR, and patterns of abnormalities can be used to identify specific types of myocarditis. 14 CMR also has prognostic utility, with persistence and extent of LGE predicting adverse outcomes including mortality and arrhythmias. 15 Finally, CMR can also be used to guide sites for endomyocardial biopsy (EMB). 9 ROLE OF BIOPSY. Traditionally, EMB has been considered the gold standard for diagnosis in patients with acute myocarditis. In cases of fulminant myocarditis, EMB can help discern the specific etiology and provide additional assistance in guiding therapy. 9 In less severe cases of myocarditis, EMB has a lower sensitivity for diagnosis than CMR and is also less likely to inform management. 2,16 EMB is also limited by low yield because of sampling error and lack of consensus on standard criteria for interpretation. 10

CONCLUSIONS

This case of fulminant myocarditis following SARS-CoV-2 infection highlights many of the severe clinical manifestations that may occur with this condition. Early recognition and implementation of supportive care (eg, ECLS) in cases such as this is critically important. Close monitoring of these patients after discharge is also paramount, as additional risks (eg, arrhythmic) may persist.

FUNDING SUPPORT AND AUTHOR DISCLOSURES

tatin. A repeat hs-TnT, 4 hours after the initial troponin was 2,382 ng/L. She was taken for urgent coronary angiography, which demonstrated normal coronary arteries. Her left ventricular end-diastolic pressure was 17 mm Hg with an arterial blood pressure of 96/65 mm Hg. Left ventriculography demonstrated mild global hypokinesis. An echocardiogram done around the same time showed moderately increased left ventricular wall thicknesses, mild global left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] 49%, Simpsons), grade II diastolic dysfunction, and a trivial to small pericardial effusion. Based on these findings, a presumptive diagnosis of viral myocarditis was made. Within a few hours of her cardiac catheterization, she developed worsening hypotension that was treated with a fluid bolus. A computed tomography scan of the abdomen and pelvis found no evidence of a retroperitoneal bleed. Over the next 12-24 hours, her clinical status deteriorated, with markedly increased work of breathing. Examination showed jugular venous distension and diffuse crackles on lung examination, and she was started on noninvasive positive pressure ventilation. She also showed signs of a low-output state, with cold, clammy extremities and drowsiness. A repeat echocardiogram showed worsening left ventricular systolic function with an ejection fraction of 30%-35%, moderately increased left ventricular wall thicknesses with hyperechoic myocardial echotexture, and a small pericardial effusion (Videos 1 and 2

/dL, N-terminal pro-B-type natriuretic peptide 19,054 pg/mL (normal <300 pg/mL), interleukin-6 2,169 pg/mL (normal <6 pg/mL) and hs-TnT 5,810 ng/L. She was started on intravenous dobutamine and administered a dose of intravenous furosemide. Her clinical status continued to deteriorate, with persistent hypotension requiring escalating doses of norepinephrine, vasopressin, epinephrine, and phenylephrine. Within the next few hours, she had 2 episodes of sustained ventricular tachycardia (VT), for which she underwent synchronized cardioversions twice and was started on intravenous amiodarone. An arterial blood gas showed severe metabolic acidosis, for which she was started on intravenous bicarbonate. On hospital day 3, she remained hypotensive with acidemia and was started on veno-arterial extracorporeal membrane oxygenation (VA ECMO), cannulating the right femoral artery and vein. Her rapid hemodynamic deterioration suggested fulminant myocarditis. Several forms of percutaneous temporary mechanical support were considered by the shock team, informed by our center's experience. Primary bridge-to-decision VA ECMO was favored because of her rapid hemodynamic compromise, need for full circulatory support, risk of worsening right ventricular failure in the setting of myocarditis, and ability of ECMO to provide adequate oxygenation should COVID-19 acute respiratory distress syndrome evolve. While on VA ECMO, continuous renal replacement therapy (CRRT) was initiated for worsening renal function. A bedside echocardiogram on hospital day 6 demonstrated severely reduced left ventricular systolic function with an ejection fraction <15%, along with increased left ventricular wall thicknesses and a small cavity size. Based on her presumed diagnosis of fulminant COVID-19 myocarditis, she was treated with 3 days of intravenous methylprednisolone (1 g/d), followed by a prednisone taper (60 mg daily initially, weaning 10 mg every 3 days). Concurrent with this, she experienced multiple episodes of nonsustained VT, for which she was continued on intravenous amiodarone and started on lidocaine.

FIGURE 1 (Figure 3 ,
13Electrocardiogram at Presentation A 12-lead electrocardiogram showing sinus tachycardia; ST-segment elevation in avR, V 1 , and V 2 ; and ST-segment depression in multiple other leads. successfully. She required a brief course of vasopressin, epinephrine, and milrinone following decannulation. CRRT was discontinued on hospital day 20, transitioning to intermittent hemodialysis. Her urine output increased with intravenous furosemide within 6 days after CRRT discontinuation, and no further dialysis was required thereafter. On hospital day 24, a repeat echocardiogram demonstrated improvement in her left ventricular systolic function with an ejection fraction of 50%-55%, normal left ventricular size, and reduced left ventricular wall thickness. Given stable and acceptable hemodynamics, she was started on metoprolol succinate, isosorbide dinitrate, and hydralazine. Cardiac magnetic resonance (CMR) was ordered to confirm the diagnosis of myocarditis and to assess more fully left and right ventricular systolic function. Diffuse hyperintensity on T 2 mapping (up to 67 milliseconds, normal <52 milliseconds) suggestive of myocardial edema or inflammation was observed Video 3). The myocardial extracellular volume fraction was significantly elevated at 39% (normal <29%), indicative of diffuse interstitial expansion. LVEF and right ventricular ejection fraction were 45% and 33%, respectively, with normal biventricular size. Right heart catheterization and endomyocardial biopsy (EMB) were also performed to exclude granulomatous myocarditis, given the arrhythmia burden. The biopsy showed scattered perivascular and interstitial inflammatory cells consisting of CD3-positive T-lymphocytes, CD20 positive B-lymphocytes, and histiocytes, along with interstitial and myocyte injury, suggestive of acute viral myocarditis. Viral immunostains for herpes simplex, adenovirus, and cytomegalovirus were negative. Congo red and iron stains were negative. There was no evidence of multinucleated giant cells, eosinophils, or granulomas (Figure 4). Her hospital course was further complicated by pseudomonas bacteremia from infection at the ECMO cannula site, for which she completed a course of antibiotics. She was discharged to home on hospital day 40 with improved ventricular function by echocardiography (Videos 4 and 5). Before discharge, she underwent placement of an implantable loop recorder (ILR) and an external defibrillator vest and guidelinedirected medical therapy for heart failure (metoprolol succinate, lisinopril, amiodarone, and furosemide)was continued. An implantable cardioverterdefibrillator was considered; however, preference was given to a wearable defibrillator, as the LVEF was >45%, and her myocarditis was considered to be an acute and potentially reversible insult. The ILR was felt to be an important adjunct, given her significant arrhythmia burden during hospitalization and its ability to help guide her need for an implantable cardioverter-defibrillator in follow-up.At her 3-month cardiology follow-up, she underwent repeat CMR(Figure 3, Video 6) that demonstrated normal left ventricular systolic function with

FIGURE 2
2Chest X-Ray at Presentation Chest X-ray, anteroposterior and lateral view showing normal heart size and pulmonary vasculature. No focal consolidations, pleural effusions, or pneumothorax. Rajpal et al an ejection fraction of 58%, a low-normal right ventricular ejection fraction of 46%, and residual linear epicardial nonischemic fibrosis involving the basal to mid inferolateral and lateral left ventricular walls, suggestive of prior myocarditis (Figure 3). Interval improvement was noted in right and left ventricular systolic function, along with resolution of myocardial edema/inflammation and diffuse interstitial expansion. As her left ventricular systolic function had improved and no significant arrhythmias were noted with interrogation of her ILR, implantation of a cardioverter-defibrillator was deferred. However, 6 months later (9 months after her initial presentation) she presented to the ED with lightheadedness and was found to be in a wide complex tachycardia (confirmed to be VT) at a rate of 176 beats/min. Interrogation of her ILR demonstrated persistence of this rhythm for 2 hours and 30 minutes. Thereafter, she underwent an electrophysiology study that demonstrated multiple VT morphologies. For this, a cardioverter-defibrillator was implanted, and she was started on antiarrhythmic drug therapy with mexiletine. She has done well in follow-up, with preserved left ventricular systolic function, improving functional capacity, and no further arrhythmias. Fulminant myocarditis is a lifethreatening condition characterized by severe myocardial inflammation with myocardial edema and myocyte necrosis. Defining features include a rapidly progressive course, with cardiogenic shock, lifethreatening cardiac arrhythmias, and multiorgan failure.

FIGURE 3
3Cardiac Magnetic Resonance Imaging During Hospitalization and Follow-Up (Top) Initial CMR. (A) Basal short-axis T 2 map. Inferolateral wall (arrow) with elevated value of 67 ms (normal <52 ms). (B) Mid short-axis T 1 map. Septal native T 1 ¼ 1,207 ms (normal <1,080 ms). (C) Basal short-axis cine. Quantitative LVEF ¼ 45%. Quantitative RVEF ¼ 33%. Small pericardial effusion. (D) Basal short-axis late gadolinium enhancement image. Note inferolateral epicardial late gadolinium enhancement (arrow). (Bottom) 3-month follow-up CMR. (A) Basal short-axis T 2 map. Inferolateral wall 48 ms. (B) Mid short-axis T 1 map. Septal native T 1 ¼ 967 ms. (C) Basal short-axis cine. Quantitative LVEF ¼ 58%. Quantitative RVEF ¼ 46%. (D) Basal short-axis late gadolinium enhancement image. Note improvement in inferolateral fibrosis compared to initial scan. CMR ¼ cardiac magnetic resonance; LVEF ¼ left ventricular ejection fraction; RVEF ¼ right ventricular ejection fraction. available and can be performed at the bedside in rapidly deteriorating patients. 3 Increased myocardial thickness caused by myocardial edema with regional wall motion abnormalities in a noncoronary distribution and normal left ventricular size represent findings consistent with myocarditis; in contrast, a dilated ventricle is more often suggestive of an alternative process. 7 Presence of regional wall motion abnormalities may introduce challenges in discerning this from an acute coronary syndrome.

FIGURE 4
4Endomyocardial BiopsyEndomyocardial biopsy showing scattered perivascular and interstitial inflammatory cell infiltrates, interstitial and myocyte injury, suggestive of acute myocarditis. Predominant CD3 T-lymphocytes fewer CD20 B-lymphocytes and CD68 histiocytes. Viral immunostains for herpes simplex virus, adenovirus, and cytomegalovirus were negative.

). For worsening hypoxemia despite noninvasive positive-pressure ventilation, invasive mechanical ventilation was initiated. Pertinent laboratory values at that time tion 98% by arterial blood gas, lactate 14.9 mmol/L Fulminant myocarditis following SARS-CoV-2 infection is rare. When present, it is characterized by severe myocardial inflammation with myocardial edema and myocyte necrosis. Cardiogenic shock, life-threatening arrhythmias, and multiorgan failure are defining features. Early institution of MCS can be lifesaving.included pH 6.96, pCO2 20.7 mEq (normal 35-45

mEq), bicarbonate 4.7 mEq (normal 22-26 mEq), pO2

247 mm Hg (normal 80-100 mm Hg), oxygen satura-

TAKE HOME MESSAGES

COVID-19 is associated with widely
ranging cardiovascular complications
that include, but are not limited to,
myocarditis, myocardial injury, stress
cardiomyopathy, thromboembolism, and
post-acute sequelae of SARS-CoV-2
infection.

TABLE 1
1Laboratory Testing at Different Time Points of the Hospitalization ALP ¼ alkaline phosphatase; ALT ¼ alanine transaminase; AST ¼ aspartate transaminase; BUN ¼ blood urea nitrogen; ECMO ¼ extracorporeal membrane oxygenation; INR ¼ international normalized ratio; NT-proBNP ¼ N-terminal pro-B-type natriuretic peptide; PT ¼ prothrombin time; WBC ¼ white blood cell.Laboratory Test

Presentation
Day 1
Day 2

ECMO
Day 1

ECMO
Day 2
Discharge
Normal Range

High-sensitivity troponin T, ng/L
1,737
2,018
0-14

NT-proBNP, pg/mL
250
19,054
0-125

C-reactive protein, mg/L
44.79
88.61
<10

Sodium, mEq/L
140
132
149
141
146
135-148

Potassium, mEq/L
4.0
5.4
3.6
5.1
4.7
3.4-5.3

Chloride, mEq/L
101
95
101
101
111
96-110

Carbon dioxide, mEq/L
23
5
21
26
24
19-32

Glucose, mg/dL
108
217
189
77
72-99

BUN, mg/dL
10
23
33
28
26
3-29

Creatinine, mg/dL
0.6
1.4
1.86
2.28
1.2
0.5-1.2

Calcium, mg/dL
9.4
9.2
8.5-10.5

Lactate, mmol/L
14.9
17.5
1.56
0.5-1.6

Anion gap
16
32
31
19
5-15

Bilirubin, mg/dL
0.4
1.0
0.2
0-1.5

AST, U/L
199
4,393
6,200
18
14-40

ALT, U/L
118
3,240
2,480
24
9-42

ALP, U/L
178
98
116
32-126

WBC, K/mm 3
10.3
11.2
26.9
12.3
3.8-10.8

Hemoglobin, g/dL
14.5
12.8
9.6
8.6
12-15.6

Platelet count
275
253
157
264
130-400

PT
17.4
Seconds

INR
1.4
Seconds

,11,16 In our case, EMB helped confirm the diagnosis of post-viral lymphocytic myocarditis, while ruling out alternative etiologies. ARRHYTHMIAS. Atrial and ventricular arrhythmias are common in fulminant myocarditis and may have multiple underlying mechanisms (eg, myocardial inflammation or edema, scar). 3,4,17 Exercise can trigger arrhythmias in acute myocarditis, and as such, current guidance cautions against exercise for 3-6 months to ensure resolution of myocardial inflammation. 18 In our patient, ventricular arrhythmias were observed at 2 different time points. During her hospitalization, polymorphic VT was felt to be the result of severe myocardial inflammation. This arrhythmia continued in the early post-ECMO period and then abated as ventricular function improved later in her course. As the acute phase resolved, no further episodes of VT were detected on her ILR. Nine months after discharge, however, she presented with symptomatic VT. CMR done at that time showed persistent LGE, and her VT was likely driven by presence of myocardial scar or persistent inflammation. Importantly, persistent LGE on CMR is an independent predictor of arrhythmias independent of ventricular function. 15,17COVID-19 AND MYOCARDITISIn a recent study that included w154,000 patients with COVID-19, the HR for myocarditis was 5.4 compared with uninfected contemporary and historical cohorts.8 Despite this, fulminant myocarditis with COVID-19 remains rare,19,20 with most reported cases being mild in severity. Autopsy studies have further suggested that although nonspecific cardiac inflammation is common with COVID-19, myocarditis meeting strict pathological criteria is rare.21 Multiple reports have also noted myocardial involvement by CMR among asymptomatic and minimally symptomatic individuals.22,23 Collectively, this has made estimation of the prevalence and incidence of myocarditis with COVID-19 quite challenging.In addition to myocarditis, other forms of cardiovascular disease may manifest after SARS-CoV-2 infection, including pericarditis, myocardial ischemia, microvascular disease, nonischemic cardiomyopathy, stress cardiomyopathy, thromboembolism, and arrhythmia. For others, cardiovascular symptoms (eg, chest pain, dyspnea, palpitations) may occur or persist, with no specific cardiac etiology identified after testing. The 2022 ACC Expert Consensus Decision Pathway on CardiovascularSequelae of COVID-19 in Adults provides a framework by which to evaluate and manage these individuals.24
J A C C : C A S E R E P O R T S , V O L . 4 , N O . 1 0 , 2 0 2 2 COVID-19 Fulminant Myocarditis M A Y 1 8 , 2 0 2 2 : 5 6 7 -5 7 5
M A Y 1 8 , 2 0 2 2 : 5 6 7 -5 7 5
J A C C : C A S E R E P O R T S , V O L . 4 , N O . 1 0 , 2 0 2 2
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.ADDRESS FOR CORRESPONDENCE
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Cases Journal Emphysematous pyelonephritis in type II diabetes: A case report of an undiagnosed ureteric colic

Samuel R Vollans email@example.com
Department of Urology
Huddersfield Royal Infirmary
Acre StreetHD3 3EALindley, HuddersfieldUK

Ranjit Sehjal email@example.com
Department of Urology
Huddersfield Royal Infirmary
Acre StreetHD3 3EALindley, HuddersfieldUK

James A Forster firstname.lastname@example.com
Department of Urology
Huddersfield Royal Infirmary
Acre StreetHD3 3EALindley, HuddersfieldUK

Karol M Rogawski
Department of Urology
Huddersfield Royal Infirmary
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Cases Journal Emphysematous pyelonephritis in type II diabetes: A case report of an undiagnosed ureteric colic
10.1186/1757-1626-1-192BioMed Central Page 1 of 4 (page number not for citation purposes) Case Report * Corresponding author
Introduction : Emphysematous pyelonephritis (EPN) is a severe acute necrotising infection of the renal parenchyma and perirenal tissue, characterised by gas formation. 90% of cases are seen in association with diabetes mellitus. We report a case of undiagnosed ureteric obstruction in a type II diabetic, leading to EPN requiring emergency nephrectomy.Case presentation :A 59-year-old type II tablet controlled diabetic woman presented complaining of a five day history of right sided abdominal pain associated with vomiting, abdominal distension and absolute constipation. There were no lower urinary tract symptoms. Past surgical history included an open appendectomy and an abdominal hysterectomy. On examination, she was haemodynamically stable, the abdomen was soft, distended, and tender in the right upper and lower quadrants with no bowel sounds. Investigations revealed a CRP of 365 and 2+ blood and nitrite positive on the urine dipstick. The AXR was reported as normal on admission, however when reviewed in retrospect revealed the diagnosis. She was managed, therefore, as having adhesional bowel obstruction and a simple UTI. After four days, a CT was organised as she was not settling. This showed a right pyohydronephrosis with gas in the collecting system secondary to an 8 mm obstructing ureteric calculus. The kidney was drained percutaneously via a nephrostomy and the patient was commenced on a broad spectrum intravenous antibiotics. Despite this, she went on to need an emergency nephrectomy for uncontrolled severe sepsis. She was discharged in good health 15 days later.Conclusion : EPN carries a mortality of up to 40% with medical management alone. Early recognition of EPN in an obstructed kidney is essential to guide aggressive management, and in the presence of continued severe sepsis or organ dysfunction an urgent nephrectomy should be carried out. Diabetic patients who are known to have renal or ureteric calculi, whether symptomatic or not, should be considered for percutanous or ureteroscopic treatment. In the acute abdomen, the plain abdominal radiograph should always be viewed with respect to general surgical, vascular and urological differential diagnoses.

Introduction

Emphysematous pyelonephritis (EPN) is a severe acute necrotising infection of the renal parenchyma and perirenal tissue, characterised by gas formation. The condition presents amongst other things with abdominal pain, septic shock, vomiting, fever, lethargy and confusion. The majority of cases reported are unilateral, occur in patients with diabetes mellitus or urinary tract obstruction, and more commonly affect on the left kidney [1,2]. We report a case of 'missed' ureteric obstruction in a type II diabetic, leading to EPN requiring an emergency nephrectomy.

Case presentation

A 59-year-old white Caucasian woman presented to the Emergency Department complaining of a five day history of right sided abdominal pain, which had got progressively worse over the preceding few hours. The pain was limited to the right side of the abdomen with no radiation, and was described as an ache. Associated symptoms included nausea, vomiting and abdominal distension. Her bowels had not been open for three days, and she had not passed flatus for the last twenty-four hours. She did not complain of any lower urinary tract or gynaecological symptoms.

Past surgical history included an open appendectomy 15 months previously and an abdominal hysterectomy. Past medical history included tablet controlled (metformin and gliclizide) type II diabetes mellitus.

On admission she was alert, orientated, apyrexial and haemodynamically stable. Examination of the cardiovascular system was unremarkeable, and the only abnormality on respiratory examination was reduced breath sounds at the right lower zone. The patient's abdomen was distended but soft, and on palpation she complained of severe pain in the right upper and lower quadrants with no guarding. Bowel sounds were absent, and PR examination was normal. FBC, U&E, CRP, Glucose, CXR, AXR and urine dipstick were ordered.

The FBC and U&E were normal (Hb12.6 g/dl, WCC11.0 × 10 9 /l, Ur 4 mmol/l, Cr 86 μmol/l), serum glucose was elevated at 12.7 mmol/L, and the CRP was grossly elevated (365 mg/l). The erect CXR was normal with no free gas under the diaphragm. A plain AXR was reported as showing gas in the transverse colon and rectum. Urine dipstick showed 2+ blood and was positive for nitrites. A sample was sent for microbiology and the patient was prescribed trimethoprim. At this stage the diagnosis of adhesional bowel obstruction was made, as well as an incidental UTI.

Though noting that the ileus was somewhat unusual, the surgical team concurred with the diagnosis, as she had been admitted with similar abdominal pains in the past under the general surgeons which had settled spontaneously. She was made "nil-by-mouth", intravenous fluids were commenced and a nasogastric tube was inserted for her persistent vomiting of bilious fluid.

Urine culture grew Escherichia coli, sensitive to Trimethoprim which was continued. Blood WCC had increased to 14.8 × 10 9 /l by Day 2, and renal function remained normal. On Day 3, a repeat urine culture was sent and this result came back on Day 4, when the patient had begun to deteriorate significantly; it revealed a growth of Escherichia coli, now resistant to trimethoprim, and an Enterococcus sp. resistant to cefuroxime. Both were sensitive to ciprofloxacin. She was thus commenced on intravenous Ciprofloxacin, Flucloxacillin and Metronidazole, and a CT scan of the abdomen was organised.

The CT scan revealed a moderate hydronephrosis, with gas in a dilated pelvicalyceal system (Figure 1) due to an 8 mm stone at the right pelvi-ureteric junction (PUJ) ( Figure  2). The right ureter was completely collapsed distal to the stone. Prompt urological input was sought, which lead to an immediate USS guided right nephrostomy with a 6-French catheter and frank pus was drained. Over the next 24 hours, the patient's condition deteriorated further, showing signs of severe sepsis with a compensated metabolic acidosis (pH 7.38, CO 2 3.3 kPa, HCO 3 -18 mmol/l, Base Excess -10 mmol/l, Lactate 8.6 mmol/l). In addition, the percutaneous nephrostomy was draining little urine, and thus an emergency right nephrectomy via a loin incision was performed after resuscitation and stabilization. Extraperitoneal dissection and excision of the kidney was CT scan showing a moderate hydronephrosis, with gas in a dilated pelvicalyceal system Figure 1 CT scan showing a moderate hydronephrosis, with gas in a dilated pelvicalyceal system.

technically challenging due to the acute timing of surgery, but proceeded without complication.

Following the operation the patient was admitted to the Intensive Care Unit for invasive monitoring, cardiovascular and respiratory support, and blood glucose control. She was extubated successfully on post-operative day 3 and returned to the ward soon after for recovery, leading to discharge, 15 days after admission. When reviewed in out-patients' clinic, she had no complaints, was free of urinary infection and had normal renal function.

The case was reviewed at the urology x-ray meeting during her recovery on the ward. In retrospect, the admission AXR showed a large calculus at the level of the L3 vertebra on the right, and gas in the right renal pelvis (Figure 3). A CT scan performed four months previously to investigate a change in bowel habit and right-sided abdominal pain, demonstrated a 7.4 mm calculus within the renal pelvis on the right side.

Discussion

EPN was first described in 1898, in association with pneumaturia as a result of gas forming pathogens [3]. The most common pathogen is Escherichia Coli (70%), followed by Klebsiella pneumoniae (29%) and Proteus [1]. These bacteria ferment sugars within the urine producing gases including nitrogen, hydrogen, carbon dioxide, and oxygen [4]. EPN occurs nearly exclusively (90%) in people with diabetes [1]. The exact pathophysiology of EPN is still unclear. This is evidenced on the observation that UTIs are very common in diabetic patients, and only a small proportion of these patients develop EPN. The factors that predispose to EPN in people with diabetes may include uncontrolled diabetes, high levels of glycosylated hemoglobin, and impaired host immune mechanisms caused by local factors such as renal tract obstruction (tumours or lithiasis).

With regard to imaging the AXR, although reported as normal, demonstrated gas in the collecting system of the right kidney and a calculus at the PUJ. In the acute abdomen, the AXR should specifically be reviewed to exclude signs of all general surgical diagnoses, as well as vascular (aneurysms) and urological differential diagnoses.

Renal USS can confirm the presence of EPN in approximately 80% of cases [5], whereas CT is 100% sensitive [6]. Thus, a CT scan is mandatory to diagnose EPN if the index of suspicion is high. The most recent CT classification of EPN is described by Huang et al [1], with minor adjustments from the previously proposed classification by Michaeli et al (1984) [7]. It essentially describes the anatomical location of gas on CT scan:

• Class 1 -Gas confined to the collecting system It is now largely accepted that nephrectomy is the treatment of choice in most patients with EPN [7]. When treated with antibiotics alone, EPN is associated with a high mortality rate (40%) [8]. Huang et al concluded that Class 1 and Class 2 EPN could be managed with percutaneous drainage and antibiotics [1]. In class 3 and class 4 EPN, the presence of fewer than two risk factors (thrombocytopenia, acute renal failure, stupor/coma and shock) indicated that percutaneous drainage and antibiotics could also be used (successful in less than 64% of cases). However, in the presence of three or more of the above risk factors, nephrectomy yielded better results. Mortality rates were 15-20% in two other case series in which nephrectomy was the treatment of choice [2,9].

Our patient had Class 1 EPN, and underwent an emergency nephrectomy following persistent deterioration despite percutaneous nephrostomy and adequate intravenous antibiotics. Thus, the authors of this case concur with others in suggesting that early nephrectomy is recommended in any severe presentation of EPN (i.e. with septic shock, severe sepsis or multi-organ dysfunction syndrome) [1,10].

Conclusion

EPN is a condition which carries major morbidity and significant mortality. Rapid and thorough assessment, prompt diagnosis and appropriate aggressive treatment is likely to reduce mortality in these life-threatening cases of urinary tract obstruction in diabetics. As 90% of EPN occurs in patients suffering from diabetes mellitus, one should consider early intervention of renal and ureteric calculi, whether symptomatic or not, to prevent potentially devastating complications of EPN.

•
Class 2 -Gas confined to the renal parenchyma alone CT scan showing an 8 mm calculi at the right PUJ Figure 2 CT scan showing an 8 mm calculi at the right PUJ.Plain AXR showing a gas filled right renal pelvis with a visible calcification, consistent with a right EPN secondary to a proximal ureteric stoneFigure 3 Plain AXR showing a gas filled right renal pelvis with a visible calcification, consistent with a right EPN secondary to a proximal ureteric stone. • Class 3a -Perinephric extension of gas or abscess • Class 3b -Extension of gas beyond the Gerota fascia • Class 4 -Bilateral EPN or unilateral EPN with a solitary kidney
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Competing interestsThe authors declare that they have no competing interests.Authors' contributionsSRV and KMR were involved in the medical management of the patient. KMR undertook the surgical interventions on the patient. SRV obtained written consent from the patient for publication of information and images regarding the case. SRV and RS carried out the literature search and produced the draft manuscript. JAF reviewed and revised the draft manuscript. All authors reviewed and approved the final manuscript.ConsentWritten informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
CRP: C-reactive protein; AXR: abdominal x-ray; UTI: urinary tract infection; CT: computed tomography; FBC: full blood count; U&E: urea & electrolytes; CXR: chest x-ray. CRP: C-reactive protein; AXR: abdominal x-ray; UTI: uri- nary tract infection; CT: computed tomography; FBC: full blood count; U&E: urea & electrolytes; CXR: chest x-ray;

Hb: Haemoglobin; WCC: white cell count; Ur: urea; Cr: creatinine; USS: ultrasound scan. References 1Hb: Haemoglobin; WCC: white cell count; Ur: urea; Cr: creatinine; USS: ultrasound scan. References 1.

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. H A Kelly, Wg: Maccallum, Pneumaturia, JAMA. 1898Kelly HA, MacCallum WG: Pneumaturia. JAMA 1898, 31:375-81.

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Emphysematous pyelonephritis: a five year experience with 13 patients. T C Ahlering, S D Boyd, C L Hamilton, J Urol. 134Ahlering TC, Boyd SD, Hamilton CL, et al.: Emphysematous pyelonephritis: a five year experience with 13 patients. J Urol 1985, 134:1086-1088.

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