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Preview: QJM - current issue

QJM: An International Journal of Medicine Current Issue





Published: Mon, 31 Jul 2017 00:00:00 GMT

Last Build Date: Mon, 31 Jul 2017 08:51:05 GMT

 



Pulmonary fibrosis in connective tissue disease (CTD): urgent challenges and opportunities

2017-07-31

Connective tissue disease associated interstitial lung disease (CTD-ILD) remains the poor cousin, with regards to specific disease modifying therapies. CTD in general and rheumatoid arthritis (RA) in particular has seen a surge of investment by industry and the provision of a range of therapies that significantly improve the quality of life for these patients.1 More recently, two novel anti-fibrotic therapies for idiopathic pulmonary fibrosis (IPF) have been shown to significantly modify disease and improve survival.2–4 Yet, for pulmonary fibrosis arising in those with CTD, there remains a desperate need to identify effective therapies.



Challenges for Zika prevention in Myanmar

2017-07-04

Myanmar reported its first case of Zika in a pregnant woman who returned from a country with active Zika transmission.1 After coming back, she visited rural townships and health officials have confined her to prevent further transmission. So far, now new cases have been reported in Myanmar. It is a fledgling democracy, which endured decades of military rule that neglected the health care sector. The per capita health expenditure is only $20 and it is one of the lowest in South East Asia.2 Myanmar is located in South East Asia, one of the regions that are highly suitable for Zika transmission (Figure 1).



Scrofula

2017-05-11

A 30-year-old lady presented with slowly growing painless swellings and non-healing sinuses on both sides of the neck for six months. There was history of evening rise of temperature, decreased appetite and weight loss. Physical examination revealed multiple enlarged lymph nodes and pus discharging sinuses in bilateral cervical and supraclavicular regions (Figure 1). Lymph nodes were matted and showed fluctuation on palpation. Tuberculin skin test was positive and erythrocyte sedimentation rate was high (84 mm per hour). A chest roentgenogram was normal and HIV serology was non-reactive. Microbiological examination of the pus discharge revealed acid fast bacilli and patient was started on first line anti-tubercular drugs.



Ramsay Hunt syndrome following middle ear surgery

2017-05-04

We present a 59-year-old woman with facial palsy 3 weeks after a right-sided tympanoplasty surgery via the endaural approach. Physical examination showed a House–Brackman grade III right-sided facial palsy. Two days after facial palsy, swelling and vesicles over the right auricle were noted (Figure 1A). Under the impression of Ramsay Hunt syndrome characterized by acute facial palsy associated with a herpetic eruption on the auricle, the patient was treated with a 2-week oral Famvir (250 mg/tid) and tapered dose of oral prednisolone (1 mg/kg). One week after treatment, the vesicles formed a herpetic crust over the auricle (Figure 1B). The patient’s facial palsy abated within 2 weeks of treatment. The appearance of the auricle and external auditory canal completely subsided after 2 months (Figure 1C). The perforated eardrum of the right ear was successfully reconstructed and the patient’s hearing acuity improved after 6 months of follow-up.



Panda sign: sarcoidosis

2017-05-03

A 54-year-old woman presented to our outpatient ophthalmology clinic complaining of eye redness, severe pain and photophobia that had persisted for 1 day. Slit lamp examination revealed she was found to have large greasy-white mutton-fat keratic precipitates on the endothelial surface of her both eyes. Physical examination showed bilateral cervical lymphadenopathy and multiple tender erythematous nodular skin swellings on both shins. The patient’s previous medical history did not suggest trauma, insect bite, diabetes mellitus or tuberculosis. The patient had previously received the Bacille Calmette Guérin vaccination, but tuberculin skin testing was negative. Histopathological examination of skin lesion and lymph node biopsies revealed non-caseating sarcoidal granuloma, and a chest radiograph revealed bilateral hilar lymphadenopathy. Furthermore, gallium-67 scanning showed symmetrical uptake of gallium-67 into the nasopharynx, lacrimal glands, parotid glands (i.e. panda sign, Figure 1A) and lower extremities (Figure 1B). On the basis of the clinical and histopathological findings, the patient diagnosed as having sarcoidosis. Sarcoidosis is a chronic granulomatous disease that can involve almost any organ in the body. The cause of this disease remains uncertain. However, a recent study showed that Propionibacterium acnes is highly associated with sarcoidosis1. The signs and symptoms of sarcoidosis can vary depending on which organs are affected. Clinical and radiographic manifestations also vary widely among individual patients. The panda sign indicates lacrimal and salivary gland gallium-67 uptake and is generally associated with other disorders, including Sjögren’s syndrome, tuberculosis, post-irradiation lymphoma and acquired immunodeficiency syndrome2. Therefore, when the panda sign is present, clinicians should consider sarcoidosis as a possible differential diagnosis.



Kayser–Fleischer ring: Wilson’s disease

2017-05-03

A 53-year-old woman presented with a hand and neck tremor to our outpatient department. The patient denied consuming tobacco, alcohol, or other recreational drugs. She also denied any loss of consciousness, head injury, seizure, or other neurological problems. On physical examination, percussion was dull and hepatomegaly was suspected. Slit lamp examination revealed bilateral Kayser–Fleischer rings (Figure 1). Her serum ceruloplasmin level was low. Subsequently, she had a previous medical history of untreated Wilson’s disease and cirrhosis for 40 years. Wilson's disease is an autosomal-recessive disorder caused by a mutation in ATP7B, thereby downregulating expression of ceruloplasmin (and consequently, its levels in the serum)—a copper transporting protein. Wilson's disease occurs in about 1 in 40 000 individuals.1 In general, symptoms usually manifest between the ages of 5 and 40 years. However, neuropsychiatric symptoms of Wilson’s disease vary widely among individual patients. These symptoms include cognitive deterioration, behavioral changes, hand tremor and dementia, and signs such as dystonia and seizures. These symptoms are sometimes confused with other disorders ranging from depression to schizophrenia, and are hence often misdiagnosed. Kayser–Fleischer rings are the most important diagnostic sign, and are observed in over 90% of patients with Wilson’s disease.2 Untreated Wilson's disease has progressive, irreversible consequences and finally results in death. Clinicians should consider this rare hereditary disease and never overlook it.



Papillon Lefevre syndrome

2017-04-26

A 12-year-old female patient presented with chief complaint of severe bleeding of gingiva and foul breath. Medical history was noncontributory with normal physical and mental development. She lost all her deciduous teeth by 5 years of age and the permanent teeth started loosening at 8 years of age, till date there is no loss of any permanent teeth. Intraoral clinical examination revealed presence of severe destructive periodontitis of all the teeth (Figure 1A). Panoramic view showed severe generalized loss of alveolar bone around all the present teeth. Dermatological examination revealed well-demarcated, brownish, hyperkeratotic areas with crustations and fissuring affecting the skin on the palmar surface of her hands and on plantar surface of her feet (Figure 1B). Severe bone loss at such a young age was found to be abnormal so a genetic analysis was carried out utilizing peripheral blood sample and subjecting it to polymerase chain reaction which revealed a mutation in CTSC gene which encodes cathepsin C. Differential diagnosis consisted of Haim-Munk syndrome and Papillon Lefevre syndrome. Haim-Munk syndrome shows symptoms such as arachnodactyly, acroosteolysis and onychogryphosis and absent in our patient which lead us to final diagnosis of Papillon Lefevre syndrome. Dental treatment consisted of systemic amoxicillin (500 mg, thrice daily) and metronidazole (400 mg, thrice daily) for 1 week along with patient education for oral hygiene followed by full mouth periodontal flap surgery. Dermatological treatment consisted of systemic acetretin (25 mg) every alternate day for 4 months and intermittent Psoralen and Ultraviolet A therapy (8-methoxypsoralen taken by oral cavity followed 45–60 min later by exposure of the skin to ultraviolet A), 20 treatments were given 3 days apart. Patient is asymptomatic at 1 year of follow-up.



Sonographic barcode sign of pneumothorax

2017-04-18

A 16-year-old female presented with dyspnea and left chest pain after a severe motor vehicle accident. Upon arrival, her vital signs were temperature: 36.2°C, pulse rate: 86/min, respiratory rate: 17/min and blood pressure: 126/78 mmHg. Physical examinations revealed decreasing breath sound over left lung field. Thoracic ultrasound showed barcode sign over left lung (Figure 1A) in M-mode and indicated the presence of pneumothorax. Chest radiograph and computed tomography confirmed the diagnosis of pneumothorax (Figure 1B and C). Because the amount of pneumothorax is small, the patient received oxygenation therapy and supportive care. Several days later, follow-up of chest radiograph showed the re-expansion of left lung, and the patient’s condition gradually improved.



Kartagener syndrome

2017-04-11

A 23-year-old woman presented to our emergency department with chief complaints of recurrent episodes of intermittent fever and productive cough with greenish phlegm for the past few days. Her medical history included frequent sneezing, rhinorrhea, nasal congestion, and ear discharge since childhood. Her vital signs were as follows: blood pressure, 112/85 mmHg; heart rate, 75 beats/min and respiratory rate, 18 breaths/min. She was afebrile. Physical examination revealed crackles over bilateral lower lungs. Laboratory work-up was unremarkable except for leukocytosis and an elevated C-reactive protein level. Chest radiograph revealed dextrocardia and bilateral infiltration in lower lungs (Figure 1A), and computed tomography scan revealed bronchiectasis with secondary infection of bilateral lower lungs (Figure 1B) and situs inversus totalis (Figure 1C). Based on the clinical presentation and radiological findings, Kartagener syndrome (KS) was diagnosed. Empirical antibiotic therapy and supportive pulmonary care were initiated, and the patient was discharged with the resolution of symptoms 1 week later.



Sugar and artificially sweetened beverages linked to obesity: a systematic review and meta-analysis

2017-04-11

Abstract
Background/Objectives
Artificial sweeteners are used widely to replace caloric sugar as one of the strategies to lessen caloric intake. However, the association between the risk of obesity and artificially sweetened soda consumption is controversial. The objective of this meta-analysis aimed to assess the association between consumption of sugar and artificially sweetened soda and obesity.
Methods
A literature search was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception through May 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of obesity in patients consuming either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method.
Results
Eleven studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and obesity. The pooled RR of obesity in patients consuming sugar-sweetened soda was 1.18 (95% CI, 1.10–1.27). Three studies were included to assess the association between consumption of artificially sweetened soda and obesity. The pooled RR of obesity in patients consuming artificially sweetened soda was 1.59 (95% CI, 1.22–2.08).
Conclusions
Our study demonstrated a significant association between sugar and artificially sweetened soda consumption and obesity. This finding raises awareness and question of negative clinical impact on both sugar and artificially sweetened soda and the risk of obesity.



Laryngeal tuberculosis: a forgotten disease

2017-04-05

A 93-year-old woman presented with a 2-month history of hoarseness and cough. The patient had never received immunosuppressive treatment, was serologically negative for HIV and hepatitis, and did not have a family history of tuberculosis. Laryngoscopy showed an ulcerated and granular lesion in the ventricular folds, larynx vestibule and bilateral vocal cords (Figure 1A). Histological analysis of the biopsy specimen revealed granulomas with caseating necrotic centers and Langhans giant cells without carcinoma. Ziehl-Neelsen staining of the bronchoalveolar lavage fluid revealed acid-fast bacilli and PCR using the fluid revealed Mycobacterium tuberculosis. High-resolution chest computed tomography showed micronodular lesions in the right lung and a lesion suggestive of tuberculosis in the apex (Figure 1B). The patient received a standard 6-month anti-tuberculous treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol). Tuberculosis is an infectious disease that is caused by M.tuberculosis. Although laryngeal tuberculosis only accounts for ∼1% of all tuberculosis cases, laryngeal tuberculosis is terrific contagious.1 Laryngeal tuberculosis has been considered to be the result of extra-pulmonary manifestations, and has often been associated with pulmonary tuberculosis. Thus, laryngeal tuberculosis should be suspected in all patients with chronic cough, hoarseness and significant dysphagia. The symptoms are often limited, although the diagnosis can be confirmed using adequate diagnostic and radiographic examinations. Tuberculosis has become a rare disease in the developed countries, but tuberculosis infections began increasing in 1985, partly because of the HIV/AIDS emerging. Also, the rise in drug-resistant tuberculosis and the outbreaks of multidrug resistant tuberculosis are serious underlying problems in the health-care infrastructure all over the world.2 Early identification can facilitate appropriate management and treatment, which can reduce the prevalence of tuberculosis and improve public health.



Coincidental coronary artery disease impairs outcome in patients with takotsubo cardiomyopathy

2017-03-14

Abstract
Background and aim
Takotsubo cardiomyopathy (TC) is an important differential diagnosis of coronary artery disease (CAD), mimicking acute coronary syndrome in clinical symptoms, biomarker profiles and ST-elevation in ECG. Absence of occlusive coronary disease is an essential criterion distinguishing both diseases. The aim of the study was to explore the influence of co-existing incidental CAD on poorer clinical outcomes and all-cause mortality in TC.
Design, methods and results
Our mono-centric study cohort constituted 114 consecutive patients diagnosed with TC between 2003 and 2015. The primary endpoint was the all-cause mortality. Additionally, we compared the incidence of thromboembolic events, life-threatening arrhythmias, cardiogenic shock and in-hospital death. There was no significant difference in gender distribution or mean age in both groups. Patients diagnosed with a co-existing CAD (n = 22), had a more pronounced cardiovascular risk profile. The all-cause mortality among patients with co-existing CAD after a 2-year follow-up was higher than those diagnosed with lone TC (22.7 vs. 5.4 %, P = 0.07). In a multivariate cox regression analysis CAD (HR 3.5, 95 %CI 1.0–11.6; P = 0.04), LVEF ≤ 35% (HR 3.8, 95% CI 0.0–0.6, P = 0.01) and cardiogenic shock (HR 3.8, 95% CI 1.2–11.3; P = 0.01) were independent predictors of the primary endpoint.
Conclusion
Our study reveals that co-existing CAD impairs the outcome in patients with TC. The diagnostic work-up for TC should therefore not necessarily hinge on ruling out CAD.



Meta-analysis of statins in chronic kidney disease: who benefits?

2017-03-14

Abstract
Background
Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted.
Aim
To determine the extent to which the effectiveness of statins varies by kidney class.
Design
Meta-analysis.
Methods
We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists’ Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM).
Results
A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant.
Conclusions
Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn.



Cardiac troponin-I as a predictor of mortality in patients with first episode acute atrial fibrillation

2017-03-11

Abstract
Background
Recent-onset atrial fibrillation (AF) is a frequent cause for presentation to the emergency department. Recent studies proposed that the addition of biomarker information might improve the prediction of clinical outcomes by enabling identification of patients at high risk.
Aim
We aimed to examine the role of cardiac troponin I as a predictor of clinical outcome in patients with first episode acute AF.
Design
Patients, 18 years or older, presenting to our hospital with a primary diagnosis of first episode acute AF were included in this retrospective study.
Methods
The association between elevated cTnI with mortality or the composite endpoint (mortality, stroke or heart failure) was examined in a univariate Cox regression model.
Results
Of the 274 study patients, 111 had elevated cTnI levels (41%). Increased cTnI was associated with older age, history of myocardial infarction, higher creatinine levels and higher heart rate (All P < 0.01). Elevated cTn was associated with an adjusted hazard ratio of 1.86 [95% confidence interval (CI) 1.17–2.96; P = 0.009] for mortality and 1.89 (95% CI 1.27–2.84; P = 0.002) for the combined endpoint.
Conclusions
Elevated cardiac Troponin I is a significant predictor of mortality and a composite endpoint of mortality, stroke or heart failure in patients presenting with first episode acute AF.



Impaired ability to grow colonies of endothelial stem cells could be the mechanism explaining the high cardiovascular morbidity and mortality of patients with depression

2017-03-09

Abstract
Background
Subjects with depression are more prone to develop cardiovascular complications. Severity of depression is associated with higher rates of cardiovascular mortality and morbidity. Several mechanisms were suggested including accelerated atherosclerosis, alteration of the cardiac autonomic response with a decrease in heart rate variability. There is evidence that circulating endothelial progenitor cells (EPCs) are decreased in patients with major depression. Our hypothesis was that patients with depression would have an impaired ability to build colonies of EPCs.
Methods
A prospective study enrolled twenty women with a diagnosis of major. All were not treated before for depression. Thirteen healthy age-matched women served as controls. All signed a consent form before recruitment to the study. Peripheral blood was drawn to build colonies of EPCs within 5 days. ELISA methods were used to measure levels of vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF).
Results
Twenty female patients with depression were recruited. The mean age was 43 ± 14 years (vs. controls 41 ± 11 years, P = 0.682), patients’ average CFU-EPCs was 7 ± 8 colonies per well (controls 31 ± 11, P = 0.0001), VCAM-1 level was 121.7 ± 3.0 ng/ml (controls 119.3 ± 3.1 pg/ml, P = 0.037), VEGF level was 6.4 ± 0.2 pg/ml (controls 5.2 ± 0.5 pg/ml, P = 0.0001). An inverse correlation was found between VEGF level and EPCs’ colonies (r  = −0.547, P < 0.001) and between age and CFU-EPCs (r = −0.576, P = 0.008).
Conclusions
We found that patients with major depression had high levels of VCAM-1 and VEGF. They also had a significant inhibition of EPCs’ colonies. An inverse correlation was found between levels of VEGF and the ability to grow colonies of EPCs in culture.



Predictors of failure to respond to fluid restriction in SIAD in clinical practice; time to re-evaluate clinical guidelines?

2017-03-01

Abstract
Background
Fluid restriction is recommended as first line therapy for Syndrome of Inappropriate Antidiuresis (SIAD), despite of lack of good evidence base to support its use, and poor efficacy in clinical practice and in the literature.
Aim
We set out to determine how many patients with well-defined SIAD had pre-treatment criteria which would predict failure to fluid restriction.
Design and methods
This was a consecutive, prospective evaluation of 183 patients with a diagnosis of SIAD in two different hospitals. Full ascertainment of the diagnostic criteria for SIAD was obtained in all patients.
Results
About 47% of patients had a urine volume <1500 ml in 24 h, 41% had initial urine osmolality > 500 mOsm/kg, 26% a Furst-equation ratio > 1. About 59% had one criterion predicting failure to respond to fluid restriction, 37% two criteria, and 3% three criteria.
Conclusions
Our data suggest that up to 60% of patients with SIAD had criteria which recent clinical guidelines suggest would predict nonresponse to fluid restriction. This may explain why the recommended first line therapy for SIAD has been shown to be ineffective.






Response: Russell’s viper envenomation: acute hypopituitarism or acute primary adrenal insufficiency

2017-02-28

We read with interest the points raised by Dr Krishnamurthy and Dr Vishnu about the distinction between acute hypopituitarism (AHP) and adrenal insufficiency related to Russell’s viper envenomation (RVE). We strongly encourage them to read the supplementary materialsupplementary material provided with our manuscript.1 Firstly, autopsy was performed on two of the four patients that died and it showed pituitary necrosis in both (Supplementary Table 2Supplementary Table 2). In the survivors (2, 3, 5), there was demonstrable hyposecretion of at least one other pituitary hormone apart from TSH and low cortisol in the acute setting (Supplementary Table 2Supplementary Table 2). In all the survivors, including the two cases without acute hormonal results (Cases 8 and 9) follow up showed persisting low cortisol, Thyroid-stimulating hormone (TSH) and Prolactin or testosterone at 3 months. Prednisolone and thyroxine replacement has been continued in all, including GH replacement for Case 9. Secondly, abnormalities in imaging are neither needed nor enough to support a diagnosis of AHP; pituitary imaging has been described to be normal in published cases of RVE-HP.2 Thirdly, we do not agree with the statement that the combination of hypotension and hypoglycemia in the setting of RVE occurs with isolated capillary leak, major bleeding, renal or hepatic dysfunction; these are probably cases of AHP that are being missed by the authors. Fourthly, the aim of our manuscript was to describe a series of well-characterized patients of RVE-AHP so that a diagnosis of AHP is suspected prospectively in this setting thereby triggering steroidal replacement therapy. As we have pointed out in our manuscript, several cases of de-novo chronic HP related to RVE continue to be reported suggesting significant under-recognition of AHP with associated mortality. We believe, and it is our practice, to make the final diagnosis of AHP retrospectively with repeat biochemical testing at follow-up after withdrawing replacement under supervision. Finally, we agree that availability of ACTH results in the acute setting could have made our manuscript more robust but funding for this test was unavailable at the time of writing this manuscript and results are usually unavailable for weeks in our institution.



Dilemmas in management of suspected venous thromboembolism in the obese patient

2016-08-24

The incidence of obesity is increasing with an estimate of over 300 million people in the world currently categorized as obese by the World Health Organization. Obesity affects all age and socioeconomic groups and is a problem in both developed and developing countries. One of the well-recognized complications of obesity is venous thromboembolism (VTE) to include both deep vein thrombosis (DVT) and pulmonary embolism (PE). Although, increased awareness of VTE has improved the outcome in most patients, the diagnosis and treatment of obese patients defined as body mass index (BMI) ≥30 kg/m2, suspected to have a VTE can present some unique challenges.