Department of Internal Medicine, Aster Medcity, Kochi, Kerala, India

Dr Anu L Ravindran

Dr Aswin Surjit

Dr Balaram Rathish

Dr Geetha Mary Philips

Department of Nuclear Medicine, Aster Medcity, Kochi, Kerala, India

Dr Shagos G S2

Mrs Sulfia Jabbar3

18 F– Fluorodeoxyglucose, 
Computed Tomography, Positron Emission Tomography scan, Fever of Unknown Origin,
Infection.


The use of 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG PET) CT represents a non-invasive nuclear medicine modality utilized for the purpose of identifying the focal point(s) associated with fever of unknown origin (FUO). The study aims to assess
both the clinical and diagnostic importance of 18F-FDG PET CT amongpatients presenting with FUO and to investigate the predictive value ofPET CT in achieving a definitive diagnosis.


Introduction

The study was done in a quaternary health carecenter in Kerala, including 38 adult patients fulfilling the criteria forFUO who underwent PET CT. Data was collected and statistical analysiswas done for the prediction value of PET CT in diagnosing FUO.

Materials and Methods

There were 77 eligible patients, 52 male and 25 female. Ofthese, eight have lost follow-up. FDG uptake was observed in 60 patients(86.9%) and 9 patients (11.7%) showed normal study. PET-CT asa diagnostic aid in FUO had 91.2% sensitivity, 33.3% specificity, and aPositive Predictive Value of 86.6%. Despite the PET CT results, amongthe 57 individuals with FUO, the final diagnosis revealed infections in20 patients (30%), non-infectious inflammatory processes in 20 patients(30%), and malignancy in 17 patients (24.6%).

Results

Fever of Unknown Etiology (FUO) is referred to as body temperature more than 38.3oC/ 101oF on at least two occasions with an illness duration of more than 3 weeks and the patient is not in an immunocompromised state. Also, the diagnosis may be unknown even after a thorough history taking, physical examination, and intense inpatient investigations(1). The etiologies for FUO can be classified into infections, non-infectious inflammatory disorders, and malignancies. The causes for FUO are influenced by the demographic characteristics, epidemiology, immune status of the patient, etc(2). The use of 18Fluorodeoxyglucose Positron Emission Tomography with low-dose Computed Tomography (18FDG PET-CT) becomes important in these patients, who at this point of the workup, still remain undiagnosed

Several studies like Ergul N et al. and Meller J et al. have reported the usefulness of PET-CT in FUO(4,5). They have demonstrated that PET CT has aided 42% to 89% of patients with FUO in reaching a final diagnosis by PET-CT(6,7). It is a non-invasive diagnostic technique widely employed in nuclear medicine, enabling the detection and localization of various foci throughout the body by assessing functional changes. The use of PET-CT in the diagnostic approach for patients with FUO is based on the metabolic characteristics of FDG. This imaging technique has the capability to offer early diagnosis, even in the absence of overt morphologic changes, define or confirm the degree of activity in equivocal structural abnormalities, and detect inflammatory processes that are poorly localized and are challenging to detect or are even missed by conventional imaging modalities(4). Fluorodeoxyglucose (FDG) exhibits uptake in tissues characterized by high glycolytic activity. This metabolic characteristic is not exclusive to malignant cells but is also observed in activated leukocytes, enabling the visualization of both acute and chronic inflammatory processes through imaging techniques(8). FDG PET-CT in the context of FUO demonstrates a high level of sensitivity and a relative non-specificity, making it a valuable tool for detecting malignancy, infection, and inflammation. In addition, FDG PET-CT has a relatively high negative predictive value

The objectives of the study are to evaluate the clinical and diagnostic significance of FDG PET-CT in patients with FUO and to analyze the prediction value of PET-CT in arriving at a diagnosis or as a diagnostic pointer in FUO. The study also demonstrates the spectrum of etiologies of FUO in South India including its age and gender-wise distribution.

The study was a prospective observational cohort study conducted between September 2017 to December 2021 at Aster Medcity, Kochi - a quaternary care center in South India. The study was conducted after clearance from the institute ethics committee (Ref. no: AM/EC/10-2017 dated 05/07/2017). The primary objective of the study was to evaluate the clinical and diagnostic significance of FDG PET-CT in a patient with a Fever of Unknown origin. The secondary objective was to perform statistical analysis for the prediction value of PET-CT in arriving at a diagnosis or as a diagnostic pointer in FUO. The sample size was calculated to be 38 based on a previous study done by Ferda et al 

We included all patients above the age of 18 years fulfilling the criteria for FUO and who were willing for PET CT. Only those patients in whom, a PET-CT was ordered by the treating physician were included in the study. FUO was defined as a body temperature of more than 38.3 0C/101 0F on at least two occasions with an illness duration of more than 3 weeks and no known immunocompromised state. Moreover, the diagnosis remains unknown after thorough history taking, physical examination, and intense inpatient investigations. Patients below the age of 18 years, pregnant ladies, patients known to have malignancy, HIV infection, and patients who had undergone surgery in the past 3 months were excluded from the study. Patients already undergone a PET-CT from another center before admission were excluded. Patients who did not gave consent to include in the study and patients who were lost to follow-up before completion of the study were also excluded. 

The basic demographic data like age, gender, comorbidities, socioeconomic status, and clinical details of the present condition were collected from electronic medical records of the hospital and patient interviews. Once the patient was identified as having a fever of unknown origin, their workup was followed up. A detailed history, clinical examination, appropriate initial lab tests, and initial imaging, to group the possible cause into a probable etiological group was done. Since there is no standardized diagnostic method for FUO, the diagnostic process is guided by the so-called “potential diagnostic clues” (PDC). PDC emerged from medical history, physical examination, and obligatory tests which potentially point toward a diagnosis. Finally, those patients in whom a PET-CT was ordered, were enrolled in this study. After the patients were identified and informed consent was taken, the PET-CT was taken. No extra tests or treatment was done as part of the study. Once the PET-CT was reported, the patient was further followed up and data on further investigations as well as a final diagnosis at discharge were obtained. A 4-week follow-up was done in patients who did not have a definitive diagnosis at the time of discharge.

Patients selected for PET-CT were instructed to fast, except for glucose-free oral hydration, for 4 to 6 hours before the injection of 296–444 MBq (8 to 12 mCi) of 18F-FDG. The patients were instructed to keep their regular drug schedule except for OHAs and insulin and was advised not to do physical overexertion. Blood glucose levels were measured before the injection and the target pre-procedure glucose level was <180 mg/dl with no additional use of glucose-control drugs. PET and CT images were acquired consecutively 50-60 min after the injection of 18 F-FDG, using a Philips Tru Flight Select 16-slice PET CT scanner. Standard Uptake Value (SUV) uptake up to 2.5 g/ml was taken as normal. Foci of increased FDG uptake were recorded. 

The descriptive variables were expressed as percentages and proportions, the continuous data was expressed using mean and standard deviation, and the Independent sample t-test was used to compare quantitative variables and the Chi-square test was used to compare discrete variables between groups. FDG PET-CT studies were evaluated for their clinical contribution. A PET-CT study showing normal findings was considered as contributory in excluding focal disease, a PET-CT study with no suggestive foci was defined as false-negative, and a PET-CT study demonstrating a focal, precisely localized disease process was considered as contributory for diagnosis. Abnormal findings in a patient with no final diagnosis of a focal disease process or with pathology identified in a location different from the site demonstrated on PET-CT were defined as noncontributory and false-positive (FP). The sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV), and accuracy were analyzed. All data were entered into a Microsoft Excel file and the Statistical Package for the Social Sciences (SPSS) version 16 for Windows was used for data analysis.

We had 77 eligible patients enrolled in the study after obtaining informed written consent. There were 52 males (67.5%) and 25 females (32.5%) (range 19-86 years) with a mean age of 50.1 years and a standard deviation of 16.45 years. Among them, 8 patients opted for no testing even though a PET CT was done and were lost to follow-up. Hence actual sample size was taken to be 69.

Of the 69 patients, 60 PET-CT studies (86.9%) showed an increase in FDG uptake whereas 9 patients (11.7%) had normal PET-CT studies. Among 52 of the 60 positive studies (86.6 %), PET-CT diagnosed the etiology of FUO and was therefore defined as true positive (TP). The remaining eight positive PET-CT study reports were non-contributory to the final diagnosis and were identified as false positives (FP).          

Among the 52 patients who had the diagnosis made by PET CT, 17 (32.7%) had infections, 18 had (34.6%) inflammation and 17 patients (32.7%) had malignancies. The etiology of 17 patients who had infections were found: 10 patients had tuberculosis, 6 patients had Kikuchi’s disease based on lymph node biopsy and 1 patient had an enteric fever which was diagnosed based on colonoscopy and biopsy with the culture of the biopsy sample. Out of the 17 patients who had malignancy, a biopsy of enlarged lymph nodes revealed various types of lymphoma in 7 patients, and a biopsy of FDG avid lesions in 10 patients revealed GIST (1 patient), carcinoma lung (2 patients), adrenal adenoma (2 patients), carcinoma colon (2 patients), and carcinoma thyroid (3 patients). Among the 17 patients who had an inflammatory process, 5 patients had thyroiditis confirmed by FNAC of thyroid, 2 patients had abnormal FDG uptake in the spinal cord with further tissue sampling showing meningitis, adult-onset Still's disease with Macrophage Activation Syndrome was diagnosed as per criteria in 2 patients based on PET-CT findings and bone marrow biopsy, 2 patients were diagnosed as SLE on subsequent retesting of autoimmune profiles, 2 patients were diagnosed to have Crohn’s disease and Diverticulosis following colonoscopy and biopsy. Five patients out of the 17 who had inflammatory processes did not undergo further testing and were diagnosed based solely on the PET-CT findings, and these included 2 cases of pyelonephritis, 2 cases of abscesses, and a single case of inflammatory polyarthritis.

PET-CT showed no abnormal FDG uptake in 9 patients. Among 4 out of 9 patients, FUO resolved spontaneously, without any evidence of inflammatory, infectious, or malignant process for a clinical follow-up period of 4 weeks. These patients were defined as true negatives (TN). Five patients with negative PET/CT had a final diagnosis of focal infection, inflammation, or malignancy, and this was taken as false-negative (FN). 

The PET-CT for the diagnosis of a disease process representing the etiology of FUO had a sensitivity of 91.2%, a specificity of 33.3%, a Positive Predictive Value (PPV) of 86.6%, a Negative Predictive Value (NPV) of 44.4 %, and accuracy of 81.1% as shown in table 1.

The final diagnosis obtained in 57 patients (82.6%) out of 69 who completed the study irrespective of PET-CT findings included an infectious process in 20 (30%) patients, inflammatory noninfectious processes in 20 (30%) patients, and malignancy in 17 (24.6%) patients. Among the 20 patients who had infections, 17 (85%) patients had focal infections, and 3 (15%) patients had disseminated infections. 

In this study, infection as a cause of FUO was seen in 11 (55%) males and 9 (45%) females, while malignancy as a cause of FUO was seen in 14 males (82.4%) and 3 females (17.6%). Out of the 69 patients who completed the study 36 cases (52.2%), belonged to the age group of 50 to 69 years. Table 2 shows the distribution of the type of disease diagnosed in each age group.

Our study focused on the clinical utility of PET CT for FUO and analyzed the statistical significance of the same as a diagnostic tool. The study proved PET-CT to be a valuable tool in diagnosing or ruling out a focal cause in 81.2% of the cases within this prospective study involving 77 patients presenting with FUO. The study reported 52 true positive cases and 4 true negative cases, indicating the clinical significance of PET-CT in providing relevant information for accurate diagnosis. In other words, positive PET-CT studies were found to be beneficial in 86.7% of the cases by either identifying the underlying cause of FUO or providing adequate guidance for subsequent management which could include invasive therapeutic procedures. This highlights the significant contribution of PET-CT imaging in improving diagnostic and treatment outcomes for patients with FUO. 

As a whole, a positive PET-CT study contributed to the final diagnosis in 75.3% of the present study population. It is important to correlate positive PET-CT studies in patients with FUO with their clinical, biochemical, and immunologic status. When clinically deemed necessary, these positive findings should be further confirmed through other imaging techniques or invasive diagnostic modalities(9).  The present study showed that the ultimate diagnosis regarding the cause of FUO consisted of an infectious process in 30% of patients, an inflammatory process in 30%, and malignancy in 24.6% of cases. These findings highlight the diverse etiological factors contributing to FUO, including infections, inflammatory conditions, and malignant diseases, emphasizing the need for a comprehensive diagnostic approach in order to accurately identify and address the underlying cause. In 17.6% of patients, no specific cause could be identified for FUO, and the condition resolved spontaneously.

In a study conducted by Dong et al. in 2011, the combined sensitivity and specificity of 18F-FDG PET/CT in detecting FUO were 98.2% (95% CI: 93.6–99.8) and 85.9% (95% CI: 75–93.4) respectively. Based on these results, the researchers recommended considering this method as one of the primary diagnostic tools for patients with FUO, especially when conventional diagnostic approaches have been unsuccessful in identifying the cause(10). The sensitivity was somewhat similar to our study, but the specificity in our study was very low as compared to this study. Our study also showed similar sensitivity to the referenced study, indicating a comparable ability to detect positive cases. However, in contrast, the specificity observed in our study was notably lower compared to the findings reported by them.

Tateuchi et al. conducted a study in 2016 and showed that 18F-FDG PET/CT is valuable in identifying the fever source among patients with classic FUO, specifically focusing on those who were immunocompetent. The study reported summarized sensitivity, specificity, and diagnostic yield values of 86% (95% CI: 81–90), 52% (95% CI: 36–67), and 58% (95% CI: 51–64), respectively. However, it is important to consider that the contribution of this method may be limited in clinical settings where infectious and neoplastic causes are less prevalent or encountered less frequently. Comparisons of test performance showed that 18F-FDG PET/CT was better than 18F-FDG PET alone in detecting causes of FUO(11). The results of this study more closely resembled those of ours with similar sensitivity and specificity profiles.

Comparing the age group presenting with FUO, out of the 77 patients presented with FUO, 46.1% of patients belonged between 50 and 69 years. Hence, the majority of the patients presenting with FUO in our center were the elderly population. Among them the cause of FUO were infections in 29.7%, non-infectious inflammatory processes in 21.6 %, and 27% malignancies. Our study revealed malignancies presenting as FUO were more common in males (82%) compared to females (18%). Infection presenting as FUO seems to be slightly higher in males (55%) as opposed to 45% in females. Among infections, Tuberculosis is the main culprit and was the diagnosis in half of the infectious cases. 

From our observation, one important advantage arising out of FDG PET CT investigation was the identification of metabolically active foci that is most likely to yield a positive result in biopsy or FNAC. This is an advantage over the conventional anatomic imaging where an enlarged lymph node that is picked up may not be the maximum metabolically active one with high FDG uptake and hence may not yield a positive result if sampled.

Previous use of antibiotics, steroids, and anti-inflammatory drugs can lead to decreased uptake of 18F FDG in a pathological area due to transient suppressed activity. The sample size we got was around 77, out of which 8 were lost to follow-up, 9 were negative and 60 were PET-positive cases. The small sample size would have impacted the accuracy of the result obtained. 

The study demonstrated that FDG PET-CT exhibited a good PPV and high sensitivity when assessing patients with FUO, aligning with previous findings reported in the literature. When evaluating the diagnostic yield of 18F-FDG PET/CT in FUO patients, it is essential to consider both positive and true negative cases, as individuals with a negative 18F-FDG PET/CT result tend to have a favorable clinical outcome. Given the absence of a reliable "gold standard" for diagnosing FUO, the early utilization of PET-CT in the diagnostic process of PUO offers the advantage of avoiding unnecessary multiple imaging procedures, ultimately leading to reduced hospital stays and decreased healthcare expenditure.

Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison’s Principles of Internal Medicine, 20e | AccessMedicine | McGraw Hill Medical [Internet]. 20th ed. McGraw Hill; 2018 [cited 2023 May 22]. 114–115 p. Available from: https://accessmedicine.mhmedical.com/book.aspx?bookid=2129

Yadav BK, Pannu AK, Kumar R, Rohilla M, Kumari S. Fever of Unknown Origin in Older Adults: A Prospective Observational Study from North India. J Assoc Physicians India. 2021 Oct;69(10):11–2. 

Shantaram V, Narendra A. Approach to the Patient with Fever of Unknown Origin. In: 23rd ed. API Medicine Update; 2013. p. 44–7. 

Meller J, Sahlmann CO, Scheel AK. 18F-FDG PET and PET/CT in fever of unknown origin. J Nucl Med Off Publ Soc Nucl Med. 2007 Jan;48(1):35–45. 

Ergül N, Çermik TF. FDG-PET or PET/CT in Fever of Unknown Origin: The Diagnostic Role of Underlying Primary Disease. Int J Mol Imaging. 2011 Mar 3;2011:1–8. 

Ferda J, Ferdová E, Záhlava J, Matějovič M, Kreuzberg B. Fever of unknown origin: A value of 18F-FDG-PET/CT with integrated full diagnostic isotropic CT imaging. Eur J Radiol. 2010 Mar;73(3):518–25. 

Kei PL, Kok TY, Padhy AK, Ng DC, Goh AS. [18F] FDG PET/CT in patients with fever of unknown origin: a local experience. Nucl Med Commun. 2010 Sep;31(9):788. 

Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison’s principles of Internal Medicine. 19th ed. McGraw-Hill Education; 2015. 

Keidar Z, Gurman-Balbir A, Gaitini D, Israel O. Fever of Unknown Origin: The Role of 18F-FDG PET/CT. J Nucl Med. 2008 Dec;49(12):1980–5. 

Dong M jie, Zhao K, Liu Z feng, Wang G lin, Yang S ye, Zhou G jun. A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin. Eur J Radiol. 2011 Dec;80(3):834–44. 

Takeuchi M, Dahabreh IJ, Nihashi T, Iwata M, Varghese GM, Terasawa T. Nuclear Imaging for Classic Fever of Unknown Origin: Meta-Analysis. J Nucl Med. 2016 Dec;57(12):1913–9.

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The Role of 18 F- Fluorodeoxyglucose Positron Emission Tomography with Low Dose Computed Tomography for Evaluation of Fever of Unknown Origin

#111827

Department of Neurosurgery, Aster CMI hospital, Bengaluru, Karnataka, India 

Umesh Srikantha

Department of Oncology, Aster CMI hospital, Bengaluru, Karnataka, India 

Girish S

Deepak Somasundar

Akshay Hari

Yadhu Lokanath

Department of Pathology, Aster reference labs, Bengaluru, Karnataka, India

Vidya M N

Adithya S Murali

Metastatic Thyroid carcinoma, Spine metastasis, Verterbal corpectomy, Circumferential Spinal fixation
No conflicts of interest
No sources of support


We report an unusual case of 55-year-old female from Ethiopia with a Thyroid swelling for 25 years, came to us with Right upper limb radiating pain and hand weakness for 7 months. MRI showed thyroid swelling–suspicious for carcinoma with metastatic involvement of C6, C7 and T1 vertebral bodies. After appropriate evaluation, she underwent Total Thyroidectomy and combined anterior-posterior approach in a single stage with complete excision of spinal lesion with spinal cord decompression and stabilization. The histopathological result was compatible to the metastasis of follicular thyroid carcinoma. Post-operative recovery was uneventful.

Differentiated thyroid cancer (DTC) account for the vast majority (90%) of all thyroid cancers and includes papillary (70–75%) and follicular (15–20%) cancers1. Follicular type thyroid cancer (FTC) is the second most frequent type of DTCs, and is more inclined to metastasize to the bone than papillary type. This characteristic is probably due to the fact that FTC usually spreads via blood, whereas papillary type prefers lymphatic route for dissemination². The treatment of DTC with bone metastasis is still controversial. Surgery or radioiodine therapy alone is usually unsatisfactory, and thus the management needs multidisciplinary collaboration. Here, we describe a case of FTC in which we provided a comprehensive treatment plan for the patient through preoperative evaluation and multidisciplinary consultation, which significantly improved the patient’s quality of life and prognosis.

A fifty-five-year-old female patient from Ethiopia, presented with complaints of Thyroid swelling for 25 years with a rapid increase in size since few years. She developed right shoulder pain for 8 months which settled with medications. Also, there was progressive weakness in right hand for 7 months, associated with burning sensation in inner aspect of right upper limb. She was initially evaluated in Addis Ababa (Ethiopia) with a spine MRI that revealed a thyroid swelling – suspicious for carcinoma with metastatic involvement of C6 & C7 vertebral bodies with compression of spinal cord and right C7 & C8 nerve roots (Figure.1 A- C). CT scan of spine showed osteolytic destruction of C6, C7 & T1 vertebral bodies along with involvement of Right C6, C7 & T1 pedicles (Figure.1 D-F). PET scan of whole body revealed primary thyroid malignancy with skeletal metastasis (Figure 2).

A multidisciplinary team involving surgical, medical oncology & nuclear medicine was involved. FNAC of the thyroid swelling was done which suggested possibility of follicular neoplasm. In view of long-standing history, better prognosis and significant spinal cord compression with neurological deficits, a decision was then made to go ahead with the surgery for Thyroid tumor and spine metastasis along with spinal cord decompression and stabilization. She underwent a combined anterior-posterior single-stage surgery with complete excision of spinal lesion with spinal cord decompression and stabilisation – a combined effort involving the surgical oncology and spine surgery team.
First an anterior cervical approach was planned and horizontal skin incision was taken (Figure 3A). Total thyroidectomy was performed by surgical oncology team. Using same incision C6 & C7 corpectomy and
tumour involving the anterior and middle columns of the spine was resected. The vertebral body defect was reconstructed with an expandable cage filled with allograft and anchored to the vertebral body with inbuilt locking screws (Figure 3B). Then patient was then turned prone, a midline skin incision was deepened in layers to expose the spinous process, lamina and facet joints along with removal of the metastatic component involving the posterior column. Once tumour resection was completed, supplemental posterior stabilisation was done with consecutive C5-D2 on left side with Right C5 and D2 pedicle screws using 3D real time navigation using intraoperative O-arm® system (Figure 4). The right C6, C7 and D1 pedicles were destroyed by the tumour and screw could not be inserted. The total duration of surgery was 12 hours and blood loss was around 500ml. Post-surgery she recovered very well and her radicular pain decreased (Figure 5). The histopathological result was compatible to the metastasis of follicular thyroid carcinoma (Figure 6).


After the surgery, the patient took thyroid hormone replacement therapy (L-T4 200 μg/d) and the TSH concentration was controlled under 0.1 mU/L. The radioactive iodine scan showed iodine accumulation in cervical lymph nodes and left femur. Hence the patient took I-131 adjuvant therapy, with a dose of 200 mCi and nine months later for the second time with the same dose. She remained asymptomatic at 12 months telephonic consultation and follow-up as was able to do daily routine and household work. She was advised to do a repeat imaging study in her country.

Follicular thyroid carcinomas (FTC) are subtypes of thyroid cancers which are slow growing tumors and are associated with a favourable prognosis except when they present with distant metastasis3. Lung and bone are the two most favoured sites of metastases4. Bone metastases from FTC tend to be multiple and more often to the ribs, vertebra and sternum5. Spinal metastases usually affect the thoracic (60%-80%), lumbar (15%-30%), and cervical vertebrae (< 10%). While the 10-year survival rate is 80-95% for patient with differentiated thyroid carcinoma, survival rate decreases approximately 40% for patients with distant metastasis

The management of Differentiated thyroid carcinoma with bone metastasis is challenging: a careful evaluation and a personalised approach are essential to improve patients’ outcomes6. Multimodal and multidisciplinary management strategy can achieve disease control and symptom relief in these tumours.

Thorough pre-operative examinations are the basic foundation for accurate diagnosis and favourable prognosis. CT of the neck and chest and MRI of the spine, pelvis, and femurs can be useful to visualize metastatic foci7. PET-CT can be applied to investigate further skeletal metastases for tumor staging8. Patients with Bone metastasis(BM) from thyroid carcinoma generally have better survival than some other carcinomas that frequently metastasise to bone, such as lung and renal cell carcinoma6.
Surgical resection has remained the first choice for the treatment of DTC.Total/near-total thyroidectomy and thyroid lobectomy are the two most accepted options9. Our patient underwent Total thyroidectomy. Resection of solitary bone metastasis, together with total thyroidectomy, could increase survival rate10. Wu et al11, who analyzed 44 patients of thyroid carcinoma with bone metastasis, showed that proper operations aiming at preventing or treating complications of metastatic bone disease appear to be useful in improving morbidity in patients with skeletal disease. Bernier et al12 retrospectively studied 109 DTC with bone metastasis, in which 24 (22%) patients were treated by complete excision of the metastasis, 60 (55%) patients were treated by partial removal, while others did not receive any surgery, with the median survival time being 6.2, 4.2, and 2.5 years, respectively (P<0.05).


The indications for the surgical intervention on bone metastasis are as follows: (a) continuous pain; (b) solitary bone metastasis;(c) insensitivity to other treatment; (d) existence or high risk factors of pathologic fracture and paraplegia;(e)obvious manifestation of neurodeficits13. Meanwhile, multiple organ metastasis and poor general condition are regarded as the contraindications for surgery.
Our patient successfully underwent combined anterior & posterior single stage complete excision of spinal lesion with spinal cord decompression and stabilisation. Adjuvant therapy can prolong survival and improve quality of life by elimination of microscopic residual or metastatic disease after surgery14. In a study of 106 cases, Qiu et al15 pointed out that radioiodine therapy could significantly decrease or at least stabilize serum Thyroglobulin level as well as alleviate pain on the bone. It could also help shrink or stabilize lesions for most DTC patients with bone metastasis. Petrich et al16 also conducted a retrospective study of 107 patients, with the conclusion that bone metastases from DTC could be treated by radioiodine therapy, despite the contrary opinion that bone metastases had general resistance to I-131 therapy 17. The dose of I-131 should be 3.7–5.5 GBq for an adult and 37 MBq/kg for a child18. However, the optimal doses are still under investigation.


Thyroid hormone replacement therapy should be given in order to rectify the resulting hypothyroidism and increase the survival rate. It is indicated that with high doses of replacement therapy, the recurrence of the cancer decreased 15. When TSH is >2 mU/L, the mortality and recurrence increase 19. However, long-term usage of thyroid hormone above physical dosage will lead to sub-clinical hyperthyroidism. The ideal aim of thyroid hormone replacement therapy is reducing the mortality and recurrence, simultaneously avoiding side effects. It is mandatory to evaluate the thyroid function periodically. Our patient took L-T4 200 μg/d and received the appropriate effect.

Differentiated Thyroid carcinomas with spinal metastases can be managed safely and effectively with a multidisciplinary team involving Surgical oncologists, Spine surgeons, medical oncologists and nuclear medicine specialists. Our case outlines the result of such team effort to treat a unique and large thyroid carcinoma with cervical spine metastasis causing vertebral destruction and spinal compression, through a single stage surgery and postoperative adjuvant therapy, to achieve good outcomes.

Ramadan, S., Ugas, M.A., Berwick, R.J. et al. Spinal metastasis in thyroid cancer. Head Neck Oncol 4, 39 (2012).

McNeeley MF, Sabath A, Linnau KF. Follicular thyroid carcinoma presenting as acute cord compression due to thoracic vertebral metastasis. Radiology Case Reports. 2012;7(3):687.

AACE/AAES Medical/Surgical Guidelines for Clinical Practice: Management of Thyroid Carcinoma. Endocrine Practice. 2001 May;7(3):202–20.

MARTIN S, MAURICE T, VATHAIRE FD, CATHERINE H, GARDET P, TRAVAGLI J-P, et al. Long-Term Results of Treatment of 283 Patients with Lung and Bone Metastases from Differentiated Thyroid Carcinoma. The Journal of Clinical Endocrinology & Metabolism. 1986 Oct;63(4):960–7.

Zettinig G, Fueger BJ, Passler C, Kaserer K, Pirich C, Dudczak R, et al. Longterm follow-up of patients with bone metastases from differentiated thyroid carcinoma - surgery or conventional therapy? Clinical Endocrinology. 2002 Mar;56(3):377–82.

Nervo A, Ragni A, Retta F, Gallo M, Piovesan A, Liberini V, et al. Bone metastases from differentiated thyroid carcinoma: current knowledge and open issues. Journal of Endocrinological Investigation. 2020 Aug 3;44(3):403–19.

Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. The Lancet Oncology. 2007 Feb;8(2):148–56.

Delank KS, Wendtner C, Eich HT, Eysel P. The treatment of spinal metastases. DtschArztebl Int. 2011;108(5):71-80. doi:10.3238/arztebl.2011.0071

Venkat R, Guerrero MA. Recent Advances in the Surgical Treatment of Differentiated Thyroid Cancer: A Comprehensive Review. The Scientific World Journal. 2013;2013:1–7.

Reddy Dorankula S, Thokala M, Kumar Mp, Pasupula A. Metastatic follicular thyroid carcinoma to the mandible. Indian Journal of Dental Research. 2012;23(6):843.

Wu K, Hou S-M, Huang T-S, Yang R-S. Thyroid Carcinoma with Bone Metastases: A Prognostic Factor Study. Clinical medicine Oncology. 2008 Jan;2:CMO.S333.

Bernier M-O, Leenhardt L, Hoang C, Aurengo A, Mary J-Y, Menegaux F, et al. Survival and Therapeutic Modalities in Patients with Bone Metastases of Differentiated Thyroid Carcinomas. The Journal of Clinical Endocrinology & Metabolism. 2001 Apr 1;86(4):1568–73.

Ramadan S, Ugas MA, Berwick RJ, Notay M, Cho H, Jerjes W, et al. Spinal metastasis in thyroid cancer. Head & Neck Oncology. 2012 Jun 25;4(1).

Sherma SI. Thyroid carcinoma. The Lancet. 2003 Feb;361(9356):501–11.

Qiu Z-L, Song H-J, Xu Y-H, Luo Q-Y. Efficacy and Survival Analysis of131I Therapy for Bone Metastases from Differentiated Thyroid Cancer. The Journal of Clinical Endocrinology & Metabolism. 2011 Oct;96(10):3078–86.

Petrich T, Widjaja A, Musholt TJ, Hofmann M, Brunkhorst T, Ehrenheim C, et al. Outcome after radioiodine therapy in 107 patients with differentiated thyroid carcinoma and initial bone metastases: side-effects and influence of age. European Journal of Nuclear Medicine. 2001 Feb;28(2):203–8.

Schlumberger M, Challeton C, De Vathaire F, Parmentier C. Treatment of distant metastases of differentiated thyroid carcinoma. Journal of Endocrinological Investigation. 1995 Feb;18(2):170–2.

Klain M, Ricard M, Leboulleux S, Baudin E, Schlumberger M. Radioiodine therapy for papillary and follicular thyroid carcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 2002 Aug;29(S2):S479–85.

Hovens GC, Stokkel MP, Kievit J, Corssmit EP, Pereira AM, Romijn JA, et al. Associations of Serum Thyrotropin Concentrations with Recurrence and Death in Differentiated Thyroid Cancer. The Journal of Clinical Endocrinology & Metabolism. 2007 Jul 1;92(7):2610–5.

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Surgical Management of Follicular Carcinoma of Thyroid with Spine Metastasis: A Case Report 

 Nikhil Gulavani

Amit Patil

Ashwini Mane-Patil

Chest wall reconstruction, Malignant chest wall tumors, Bone cement.

Chest wall neoplasms are a heterogenous group of tumors that are challenging to both diagnose and treat. They can arise from any soft tissue or bony structures around thoracic cavity. They can be either primary or metastatic, and either symptomatic or asymptomatic. Malignant rib tumors include multiple myeloma, chondrosarcoma, osteosarcoma and Ewing’s sarcoma which typically manifest as painful, rapidly growing large palpable masses. Desmoid tumors and neurogenic tumors are benign but locally aggressive rare tumors of chest wall. Incorrect diagnosis, incomplete resection and unsuccessful reconstruction of large thoracic wall defects have resulted in high rates of perioperative morbidity and mortality. Chest wall resection and reconstruction is the primary surgical option for chest wall tumors. This surgery involves the removal of one or more ribs to extract the tumor, followed by reconstruction to recreate a normal appearance after invasive surgery. This involves prosthetic materials, 3D printing- Titanium Powder light weight implants and/or rotation of muscle flaps.  

We present a case of 70 years old female who presented to us with painless hard swelling involving left chest, at inner aspect of left breast. It gradually increased in size and was mildly painful. On examination hard lump was palpable in inner aspect of left breast, which was involving 5th and 6th rib and encroaching over the costochondral junction and was immobile, the overlying breast was mobile over the lump. Core Biopsy was reported as low-grade spindle cell tumor and immunohistochemistry was suggestive of low-grade spindle cell proliferation probable mediastinal fibrosis – spindle cell express SMA focally and negative for Desmin, CD34, Beta catenin, STAT-6 and S-100 protein. She defaulted for the advised surgery, and presented to us after 7-8 months with huge painful enlargement of swelling.

CECT thorax was done which showed well-defined mild heterogeneously enhancing lobulated soft tissue density lesion of approximate size 10 x 9.3 x 7.1 cms seen epicentred in chest wall on left side paramedian anterior aspect of lower chest causing erosion of adjacent 4th to 6th ribs costo-chondral junction, intrathoracicextrapleural component lesion indenting over adjacent right atrium of heart with distinct interface between lesion and pericardium and adjacent volume loss of lung. Anteriorly lesion was seen up to subcutaneous plane. After preanaesthetic evaluation, patient underwent surgery. Incision was taken along the left inframammary crease and breast was lifted to expose the tumor. Then wide excision of tumor along with full thickness resection of 4th to6th ribs along with part of serratus anterior with adequate margins. In view of low-grade spindle cell proliferation and probable mediastinal fibrosis (benign) as reported on IHC, sternal bony margin of 2 cm was not considered. The chest was full thickness defect was reconstructed by bone cement wrapped in the prolene mesh which was secured to the cut margins of resected ribs with no.1 prolene sutures. Pectoralis major local rotation flap was mobilized to buttress the reconstructed area. Left intercostal drain was placed and suction drain was placed at the reconstructed site below the pectoralis muscle. Duration of surgery was 150 minutes with total blood loss of 150 ml. Final histopathology reported as Low-grade spindle cell tumor with wide and adequate soft tissue and bony margins microscopically free of tumor. Patient was discharged in stable condition on post operative day 5, with all drains removed and no complications. Although 3DPrinting with Titanium implant is the standard of care, we performed local modification with Prolene mesh coupled with bone cement, as second tier cities like us are financially challenged and also lack local expertise for 3D titanium implants. On follow up, patient was stable and asymptomatic, without any mesh and bone cement related complications. Patient is disease free till date on latest follow-up 1 month back.

Muscular, vascular, fibrous and fibrohistiocytic, peripheral nerve, osseous and cartilaginous, adipose, hematologic, and cutaneous are the eight fundamental diagnostic categories for malignant chest wall tumours. But some cancerous tumours that grow in the chest wall don’t necessarily fall into any of these categories (eg, Ewing sarcoma and synovial sarcoma). Malignant chest wall tumours are characterised by large, painful, palpable masses. Chest radiography, the modality most usually used for initial evaluation, can detect cortical damage. Chest radiography is less effective than computed tomography at detecting calcified tumour matrix and cortical damage. Magnetic resonance imaging is frequently helpful in more precisely identifying and localising the tumour when determining the presence and extent of tumour invasion. Due to considerable morbidity and mortality considerations, chest wall resection and reconstruction surgery is a challenging therapy option for thoracic surgeons. Extensive chest wall resections now have more tolerable morbidity and fatality rates thanks to advancements in anaesthesia, ICU care, thoracic surgery, and reconstructive procedures. Defects smaller than 5 cm in size in any location and defects up to 10 cm in size located posteriorly do not generally require reconstruction, while larger defects and most defects in the anterior region do require reconstruction. For the majority of chest wall cancers, wide surgical excision is the most beneficial course of action. Less morbidity and mortality rates have been observed following chest wall excision due to advancements in reconstructive procedures and postoperative patient care [1]

Accurate diagnosis, extensive surgical removal, and suitable restoration of significant chest wall abnormalities are essential for successful therapy [1]. The reconstruction of chest wall deformities must take into account a variety of parameters [2]. Even if the defect’s size and location are crucial, a reconstruction may be significantly changed by the patient’s medical history and the specifics of the wound. If a full-thickness reconstruction is necessary, both the thorax’s structural stability and the soft tissue coverage must be taken into account [2,5,6]. After resection, stability and integrity are required to prevent chest wall collapse. Silicone, Teflon, acrylic materials, or a sandwich of Prolene mesh and bone cement have all been used to achieve structural integrity [1,3]. To buttress the deficiency if necessary, we frequently use a bone cement sandwich with prolene mesh and myocutaneous flap. According to Daigeler and colleagues [7], neither the size nor the site of the resection appreciably impaired pulmonary function, which was only mildly diminished. They came to the conclusion that thoracic wall reconstruction offers great stability to sustain pulmonary function, although there are significant postoperative pain and sensory abnormalities [4]. In surgical procedure, the skeletal chest wall defect is fixed using a bone cement-prolene prosthesis after the resection is complete. The defect’s vertical and horizontal dimensions are measured after the chest wall has been resected. To avoid heat damage to nearby structures during hardening, bone cement is combined with solution in a receiver outside the body. 

In order to simulate the bone cement to the resection borders of the chest wall defect, it is then spread over the two-layer Prolene mesh. Use a sterile ruler to gauge the size of the defect or excision. Nonresorbable interrupted sutures are used to firmly attach the edge of the two-layer Prolene mesh to the defect in the chest wall. To return the chest wall’s natural form, the underlying lung is ventilated using normal tidal volumes and positive end-expiratory pressure. After covering the soft tissue with soft tissue, a two-layer Prolene mesh is used to reconstruct the chest wall, giving it an aesthetic aspect. Chest wall resection complications are frequent, ranging from 46 to 69% [5]. The most frequent issues are respiratory ones, which account for 24% of all reported cases and include pneumonia, acute respiratory distress syndrome, and atelectasia. 8 to 20% of the patient group is said to experience wound complications like infection, dehiscence, and hematoma [7].

Broad resection with tumor-free margins is essential for the long-term survival of patients with malignant chest wall tumours. Numerous medical developments have made it possible to successfully repair the chest wall, particularly by using prosthetic materials like the Prolene mesh and bone cement sandwich.

Kilic D, Gungor A, Kavukcu S, Okten I, Ozdemir N, Akal M, et al. Comparison of mersilene mesh-methyl metacrylate sandwich and polytetrafluoroethylene grafts for chest wall reconstruction. J Invest Surg. 2006;19(6):353–360. doi: 10.1080/08941930600985694.

Martini N, McCormack P, Bains M. Chest wall tumors: clinical results of treatment. Vol 2. Philadelphia: WB Saunders; 1987. p. 285.

Mansour K, Thourani V, Losken A, Reeves J, Miller JJ, Carlson G, et al. Chest wall resections and reconstruction: a 25-year experience. Ann Thorac Surg. 2002;73(6):1720–1726. doi: 10.1016/S0003- 4975(02)03527-0.

Daigeler A, Druecke D, Hakimi M, Duchna H, Geortz O, Homann H, et al. Reconstruction of the thoracic wall-long-term follow-up including pulmonary function tests. Langenbecks Arch Surg. 2009;394(4):705–715. doi: 10.1007/s00423-008-0400-9.

Hsu P, Hsu H, Lee H, Hsieh C, Wu Y, Wang L, et al. Management of primary chest wall tumors: 14 years’ clinical experience. J Chin Med Assoc. 2006;69(8):377–382. doi: 10.1016/S1726-4901(09)70276-X.

Incarbone M, Pastorino U. Surgical treatment of chest wall tumors. World J Surg. 2001;25(2):218–230. doi: 10.1007/ s002680020022

Chapelier A, Macchiarini P, Rietjens M, Lenot B, Margulis A, Petit J, et al. Chest wall reconstruction following resection of large primary malignant tumors. Eur J Cardiothorac Surg. 1994;8(7):351– 356. doi: 10.1016/1010-7940(94)90028-0.

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A Two-Layer Prolene Mesh Coupled with Bone Cement and Local Myofascial Flap Reconstruction for a Chest Wall Tumor

Internal Medicine Trainee, Department of Internal Medicine, Aster Medcity, Kochi, Kerala

Dr Georgy George Kuruvila

Lead Consultant and HOD, Department of Internal Medicine, Aster Medcity, Kochi, Kerala.

Consultant, Department of Anesthesia and Critical Care, Aster Medcity, Kochi, Kerala.

Dr Anuroop Balagopal

Consultant, Department of Nephrology, Aster Medcity, Kochi, Kerala

Dr Bipi P K

Rhabdomyolysis, covid19, creatine kinase (CK), myoglobinuria, post infectious myositis, myocardial infarction

Rhabdomyolysis may result from trauma, extreme physical exertion, prolonged immobilization, temperature induced states such as neuroleptic malignant syndrome, malignant hyperthermia. Massive necrosis manifested as limb weakness, myalgia, swelling and commonly gross pigmenturia without hematuria is the common denominator of both traumatic and non-traumatic rhabdomyolysis. Here is the case of a 46 year old male who presented with rhabdomyolysis with dermatological manifestation and complicated by Acute Kidney Injury (8-20% incidence) following an unknown etiology. A multidisciplinary approach for search of etiology, early initiation of treatment and full-fledged therapy has served in bringing him back to normal life.

Rhabdomyolysis is a complex clinical condition with rapid dissolution of injured skeletal muscle. It ranges from an asymptomatic illness with elevation in Creatinine Kinase level to a life threatening condition associated with extreme elevations in CK, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Our patient, a 46 year old male was diagnosed with rhabdomyolysis with symptoms ranging from severe muscle spasm to severe oliguric renal failure and multisystem involvement. He had typical cutaneous manifestations and features of sepsis which account to less than 10% of the total cases of rhabdomyolysis reported so far.

A 46 year old male, a goldsmith by profession, presented to our Emergency Department with severe muscle spasm, typically prominent in proximal muscle groups, such as the thighs, shoulders, lower back and calves. He also had other symptoms like muscle stiffness and cramping which progressed to extreme difficulty in walking over a span of 2 weeks. He had prodromal flu like symptoms, loose stools and respiratory distress and was tested Covid19 positive. He initially consulted in a local hospital and sought symptomatic management as an outpatient and was temporarily relieved of symptoms after which he went in home isolation. Three days later, he again developed a sudden onset of high grade fever with evening rise of temperature and took homeopathic medications for the same. But with worsening of existing symptoms and severe Acute gastroenteritis, he was admitted in Covid ward. Inflammatory markers were initially normal. Routine blood investigations showed hyperkalemia and elevated transaminases. All tropical and viral markers were sent but reported negative. His serum Creatinine kinase levels were checked in view of persisting myalgia and showed>24000 U/L(fig-1).

As the symptoms persisted, a CT Chest with Abdomen was taken which showed mild bulky bilateral kidneys with perinephric stranding likely to be pyelonephritis but there were no further spikes of fever or any evidence of urosepsis substantiating CT findings. On the second day of hospital stay, he developed tachypnea and was oliguric. He was shifted to Covid ICU and was started on Lasix infusion. On day 2 of ICU stay, respiratory symptoms worsened, became hypotensive and was initiated on Bipap and inotropes. Possibility of post infectious myositis/autoimmune myositis was considered and was started on low dose steroids. On day 3 of ICU stay oliguric renal failure set in and he was brought to our center for further management. On arrival, he was drowsy and tachypneic, and had generalized anasarca and myoglobinuria. There was no history of drugs or alcohol intake. Bullous eruptions with local heating sensation were noted extensively over both upper and lower limbs. Well demarcated erythematous swollen plaques were noted on the right side of cheek and chest wall. Blood investigations done was suggestive of neutrophilic leukocytosis (TC 29000), raised inflammatory markers (D dimer- 5870mg/L,LDH- 3622 mg/L, ferritin- 3005mg/L), impaired renal functions (S.creatinine-2.87 mg/dl) (fig-2) elevated transaminases (SGOT-1392U/L, SGPT-290 U/L) and alarmingly elevated creatinine kinase of 1,21,400U/L. ABG revealed severe metabolic acidosis and hyperkalemia.

Tropical fever works up was repeated which turned out to be negative. A provisional diagnosis of Rhabdomyolysis with oliguric Acute Kidney Injury, metabolic acidosis with secondary hepatitis was made post Covid was made. He was started on empirical intravenous antibiotic therapy, intravenous furosemide, Bipap ventilation, NAC infusion and other supportive medications. An intense interdepartmental approach comprising dermatology, neurology, nephrology and gastro medicine was involved. Hemodialysis was initiated in view of oliguric renal failure and metabolic acidosis.
in view of the cutaneous manifestations secondary to Rhabdomyolysis, skin biopsy was advised. With the existence of a scaly facial rash with accompanying muscle tenderness, possibility of an autoimmune condition was also considered. ANA profile was sent which turned out to be negative. Skin and muscle biopsy showed mild muscle inflammation, however had no features to explain myositis. He gradually developed foot drop and a nerve conduction study was done to elucidate the findings which showed bilateral axonal motor neuropathy. During the course of hospital stay, he again developed spiking fever and cultures yielded growth of Staph haemolyticus and antibiotics were optimized.


Meanwhile, he was tested negative for Covid19. Few days later he developed acute abdominal pain with 2 episodes of hematemesis and melena. A CECT Abdomen was done which revealed retroperitoneal and intraperitoneal hematoma near duodenum. He was hence kept in continuous RT ryle’s tube aspiration. Multiple blood transfusions were done to combat hemoglobin drop and stabilized. Patient showed improvement and was shifted out to the ward where he was keeping well for nearly two days. During the ward stay, he developed aspiration pneumonitis and was shifted back to ICU. Adding to the gruesome situation, he also developed respiratory acidosis, was intubated and put on a mechanical ventilator. Bronchoalveolar lavage was sent which grew Pseudomonas and Klebsiella species. Culture sensitivity reports were sensitive to Colistin and hence antibiotics were escalated. Tracheostomy was done in view of prolonged need of mechanical ventilation. He tremendously improved during the subsequent days, became hemodynamically stable and was switched over to rental Bipap. After continuous sessions of hemodialysis and adequate tracheostomy tube care, his general condition improved, renal functions stabilized and urine output improved. Hence was discharged on supportive measures.

Three months later, he was decannulated out of the tracheostomy tube by seeking optimal aseptic measures and nephrology consultation was sought to nullify any further indications for hemodialysis. Post decannulation period was uneventful. Regular OPD reviews were done following that, repeat blood investigations were normal and was back to his normal self.

Rhabdomyolysis is a potentially life threatening syndrome. In severe form it is characterized by muscle necrosis and the release of intracellular muscle constituents into circulation. It’s characterized by markedly elevated creatinine kinase levels along with muscle pain and myoglobinuria. The disease can vary from asymptomatic elevation in serum enzymes to life threatening disease associated with renal involvement and dyselectrolytemia. This is due to skeletal muscle death caused by reactive oxygen species from mitochondrial dysfunction, which has occurred in response to rise in intracellular free ionized calcium and resultant skeletal muscle contractility.

From studies done by Gearoid et al[1] and Giorgia et al[2], the most frequently associated clinical conditions include exogenous toxins (46%), trauma (26%), immobilization (18%) and sepsis (10%). The characteristic triad of rhabdomyolysis include dark urine (due to myoglobinuria), muscle pain and weakness[3][4][5][6]. Muscle pain here will be prominent in proximal muscle groups.
The hallmark of the disease is an elevation in CK and other serum muscle enzymes. When the aetiology is a crush injury or infection, there will be marked elevation of acute phase reactants and peripheral WBC count, while these will be normal or minimally raised in other aetiologies like toxin induced or electrolyte derangements[ 7]. Aspartate aminotransferase was elevated in 93.1% and alanine aminotransferase in 75% of rhabdomyolysis cases in which CK was greater than or equal to 1000units/L[7]. Skin changes of ischemic tissue injury, such as discoloration or blisters, may also be seen but are present in less than 10 percent of patients[5][6].


Three main differential diagnoses were considered in this case in view of presence of myalgia, elevated CK and dark urine. The first one is Myocardial infarction where the cardiac troponin and CK-MM will be elevated and there will be ischaemic chest pain or specific ECG signs. The next differential is Immune-mediated necrotizing myopathy, where there will be a history of use of statins[15] along with markedly elevated CK with generalized weakness which improves on immunosuppressant therapy[6][8][9][10]. The third differential considered here was Inflammatory myopathy where the patient exhibits myalgias, elevated CK and myoglobinuria[ 11] along with a chronic clinical progression. The systemic features associated with inflammatory myopathies such as dermatomyositis will be present here and there will be relatively stable laboratory abnormalities compared to rhabdomyolysis. Electromyographic or histopathological changes suggestive of myositis are usually absent in rhabdomyolysis cases[12][13][14].

In this case, the aetiology is idiopathic, probably an unnoticed COVID19 disease. The role of homeopathic drug use and heavy metal exposure (gold) does not seem to have caused the disease here, as these were not during the acute timeline of the current presentation. The use of statins, immunosuppressant drugs, alcohol or other toxins were ruled out[6][8][9][10]. Skin and muscle biopsy samples were taken and histopathologically ruled out myositis, dermatomyositis and other immune mediated necrotizing myopathy or inflammatory myopathy. His cardiac troponin and CK-MM were within normal limits and there were no clinical features pointing to cardiac involvement in this case. This case is hence a very rare presentation of Rhabdomyolysis, as the presence of dermatological complications[5][6] and associated sepsis is found in less than 10% of total rhabdomyolysis presentations. The mortality of this case was calculated by Gearoid et al[1] and it was more than 61.2%.

Rhabdomyolysis is caused by a triad of symptoms including myalgia, weakness and myoglobinuria, with an elevation in CK level ceiling the most sensitive test for muscle injury-induced rhabdomyolysis. A correlation between flu-like illness and elevated CK levels may exist further supporting the hypothesis that direct myocyte invasion by the virus may be a key component in pathogenesis. Additionally, with the peak incidence of Covid19 pandemic, it should remain in the differential for unexplained rhabdomyolysis.

McMahon GM, Zeng X, Waikar SS. A risk predicon score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013 Oct 28;173(19):1821-8. doi: 10.1001/jamainternmed.2013.9774. PMID: 24000014; PMCID: PMC5152583.

Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluaon of 475 hospitalized paents. Medicine (Balmore). 2005 Nov;84(6):377-385. doi: 10.1097/01.md.0000188565.48918.41. PMID: 16267412.

Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur J Intern Med. 2007 Mar;18(2):90- 100. doi: 10.1016/j.ejim.2006.09.020. PMID: 17338959.

Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Balmore). 1982 May;61(3):141-52. doi: 10.1097/00005792- 198205000-00002. PMID: 7078398.

Warren JD, Blumbergs PC, Thompson PD. Rhabdomyolysis: a review. Muscle Nerve. 2002 Mar;25(3):332-47. doi: 10.1002/mus.10053. PMID: 11870710.

Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care. 2005 Apr;9(2):158-69. doi: 10.1186/cc2978. Epub 2004 Oct 20. PMID: 15774072; PMCID: PMC1175909.

Weibrecht K, Dayno M, Darling C, Bird SB. Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury. J Med Toxicol. 2010 Sep;6(3):294-300. doi: 10.1007/s13181-010-0075-9. PMID: 20407858; PMCID: PMC3550495.

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Post Covid Rhabdomyolysis with Rare Cutaneous Manifesta

The journey of GLP-1 Agonists and Ozempic in diabetes management has been marked by remarkable advancements and promising developments. These drugs have redefined the way healthcare professionals approach the treatment of type 2 diabetes and obesity, offering a comprehensive and personalized approach that goes beyond glycemic control.

In the dynamic landscape of diabetesmanagement, the last few decades havewitnessed remarkable advancements in
treatment options. Among these innovations,GLP-1 agonists, with Ozempic (semaglutide)at the forefront, have been transformingthe lives of individuals grappling with thischronic condition.
Healthcare professionals in the field of diabetescare are continuously seeking innovativetherapies that efficiently control blood glucoselevels and address the multifaceted challengesconfronted by patients.


The intertwined epidemics of obesity and type2 diabetes present substantial global health andeconomic burdens. Recent pharmacotherapeuticadvances have given rise to innovative medicationsaddressing not only glycemic control
but also substantial weight loss. A notablebreakthrough is Ozempic (semaglutide), a GLP-1receptor agonist (GLP-1 RA), demonstratingpromising efficacy in managing type 2 diabeteswhile inducing significant weight loss.


Traditional treatments for type 2 diabetesprimarily emphasize glucose control, oftenneglecting the critical issue of weight management.Obesity significantly exacerbates insulinresistance and impairs glycemic control. Consequently,
there is an urgent need for pharmacologicalinterventions that not only enhance glycemiccontrol but also address the obesity epidemic.Ozempic (semaglutide), a GLP-1 RA, represents apromising pharmaceutical that offers a comprehensiveapproach to managing type 2 diabetes,addressing both hyperglycemia and obesity.


GLP-1 Agonists, also known as incretin mimetics,constitute a medication class primarilyemployed in type 2 diabetes mellitus treatment.These drugs emulate the actions of endogenousGLP-1, a hormone secreted by intestinal cells
in response to food ingestion. GLP-1 plays apivotal role in regulating blood glucose levels bystimulating insulin secretion, inhibiting glucagonrelease, retarding gastric emptying, and promotingsatiety. Ozempic's primary mode of actioncenters on GLP-1 receptor activation, primarilylocated in pancreatic beta cells. By emulatingendogenous GLP-1, Ozempic stimulates insulinsecretion in a glucose-dependent manner, reducingpostprandial hyperglycemia. Additionally, itcurbs glucagon secretion, thereby slowing hepaticglucose production. Beyond glycemic control,Ozempic significantly influences appetite regulationand energy balance. Activation of GLP-1receptors in the central nervous system triggersincreased satiety and reduced food intake, contributingto the remarkable weight loss observed
in clinical trials.


Numerous clinical trials consistently reportOzempic's efficacy in achieving weight lossamong type 2 diabetes patients. Trials such asSUSTAIN and STEP consistently demonstratesubstantial reductions in body weight among participants
receiving Ozempic compared to placebo,ranging from 5% to 15% of initial body weight,contingent on dosage and trial duration. Notably,Ozempic's weight loss effects are durable over thelong term, as evidenced by the SUSTAIN-6 trial,
underpinning its role as a weight managementstrategy.


Ozempic has exhibited general tolerability inclinical trials, with typically mild to moderateadverse events. Commonly reported side effectsencompass gastrointestinal symptoms such asnausea, vomiting, and diarrhea, often diminishing
with continued use and manageable throughdose titration. Hypoglycemia rates with Ozempicare notably low, particularly when compared tosome other antidiabetic medications. Nonetheless,caution is warranted when prescribingOzempic to patients concurrently taking sulfonylureasor insulin.


Ozempic obtained FDA approval in December2017 and has subsequently received approvals innumerous countries, a testament to its efficacyand safety profile.

Semaglutide, the active component of Ozempic,garnered attention for its potential in obesitytreatment, with FDA approval in 2021 for longtermweight management in adults with obesity.This marked a milestone in combating obesityand expanded possibilities for healthcare professionalsseeking effective treatments.

Semaglutide, as evidenced in clinical trials,demonstrated cardiovascular benefits by reducingthe risk of major adverse cardiovascularevents (MACE) in patients with type 2 diabetes.This positions it favorably in guidelines for diabetes
and cardiovascular risk management.


Ozempic's story continues to evolve asongoing research explores its applications inother conditions, such as non-alcoholic steatohepatitis(NASH) and Alzheimer's disease,showcasing the versatility of GLP-1 Agonists.

The journey of GLP-1 Agonists and Ozempicin diabetes management has been markedby remarkable advancements and promisingdevelopments. These drugs have redefinedthe way healthcare professionals approachthe treatment of type 2 diabetes and obesity,offering a comprehensive and personalizedapproach that goes beyond glycemic control.
As research continues to unveil new possibilitiesand applications for these drugs, the futureof diabetes management looks brighter thanever. Healthcare professionals, armed withknowledge, dedication, and a patient-centeredmindset, are poised to make a profound differencein the lives of individuals living withdiabetes, ensuring that they receive the bestcare and the brightest future possible.


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september-2023

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