diagnosis

Mitochondrial and lysosomal dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) leading to deficient energy production and defects in phagocytosis in endosomal-lysosomal pathway respectively. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of inheritance that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. In this review article, we summarized the spectrum of mtDNA depletion disorders along with minor learning of lysosomal storage diseases. This current article offers a perspective on the role of genetics in medical practice and how this role may evolve over the next several years.

Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.

Objectives: To describe a patient with facial-onset sensory-motor neuronopathy (FOSMN) that later developed Huntington’s disease (HD). Case report: A 62-year-old woman complained of progressive dysphagia 8 years before referral. At initial evaluation, there was excessive salivation, dysphagia, and sensory-motor trigeminal impairment. Denervation was noted on the upper limbs and the tongue. Blink reflexes were abolished. Genetic study of amyotrophic lateral sclerosis (ALS)-related genes was normal. She was diagnosed with FOSMN syndrome. Her clinical state progressively worsened with corneal anesthesia, severe denutrition, right arm and axial weakness. Seven years after referral, she was unable walk and developed generalized chorea. Abnormal huntingtin gene repeat expansion confirmed the diagnosis of HD. She died 16 years after onset of dysphagia. Conclusion: Cases with both HD and ALS have already been reported but not FOSMN and HD, to our knowledge. Some FOSMN cases have been linked to ALS-related gene mutations and HD phenocopies have been associated with C9ORF72 repeat expansions. Recently, huntingtin repeat expansions were described in the ALS population. Although a chance association cannot be excluded, data from the literature are in favor of a pathogenic relationship between FOSMN and HD in this particular case. We suggest that huntingtin gene be more systematically studied in patients with FOSMN.

Huntington’s disease (HD) is an incurable neurodegenerative disease that causes involuntary movements, emotional lability, and cognitive dysfunction. HD symptoms usually develop between ages 30 and 50, but can appear as early as 2 or as late as 80 years. Currently no neuroprotective and neurorestorative interventions are available. Early multimodal intervention in HD is only possible if the genetic diagnosis is made early. Early intervention in HD is only possible if genetic diagnosis is made at the disease onset or when mild symptoms manifest. Growing evidence and understanding of HD pathomechanism has led researchers to new therapeutic targets. Here, in this article we will talk about the multimodal treatment strategies and recent advances made in this field which can be used to target the HD pathogenesis at its most proximal level.

The Coronavirus disease-2019 (COVID-19), has become a worldwide pandemic and the scientific communities are struggling to find out the ultimate treatment strategies against this lethal virus, Severe Acute Respiratory Syndrome Coronavirus–2 (SARS-CoV-2). Presently, there is no potential chemically proven antiviral therapy available in the market which can effectively combat the infection caused by this deadly virus. Few vaccines are already developed but it is not clear to the scientific community how much efficient they are to combat SARS-CoV-2. Mode of transmission and symptoms of the disease are two important factors in this regard. Rapid diagnosis of the COVID-19 is very much important to stop its spreading. In this scenario, a complete study starting from symptoms of the disease to vaccine development including various SARS-CoV-2 detection techniques is very much required. In this review article, we have made a partial analysis on the origin, virology, global health, detection techniques, replication pathways, doses, mode of actions of probable drugs, and vaccine development for SARS-CoV-2.

Background: In France, from 30% to 35% of children suffer from multiple food allergies (MFA). The gold standard to diagnosis a food allergy is the oral food challenge (OFC) which is conducted in a hospital setting due to risk of anaphylaxis. The aim of this study was to evaluate an algorithm to predict OFCs at low risk of anaphylaxis that could safely be performed in an office-based setting. Methods: Children with MFA and at least one open OFC reactive or non-reactive to other allergens were included. The algorithm was based on multiple clinical and biological parameters related to food allergens, and designed mainly to predict “low-risk” OFCs i.e., practicable in an office-based setting. The algorithm was secondarily tested in a validation cohort. Results: Ninety-one children (median age 9 years) were included; 94% had at least one allergic comorbidity with an average of three OFCs per child. Of the 261 OFCs analyzed, most (192/261, 74%) were non-reactive. The algorithm failed to correctly predict 32 OFCs with a potentially detrimental consequence but among these only three children had severe symptoms. One hundred eighty-four of the 212 “low-risk” OFCs, (88%) were correctly predicted with a high positive predictive value (87%) and low negative predictive value (44%). These results were confirmed with a validation cohort giving a specificity of 98% and negative predictive value of 100%. Conclusion: This study suggests that the algorithm we present here can predict “low-risk” OFCs in children with MFA which could be safely conducted in an office-based setting. Our results must be confirmed with an algorithm-based machine-learning approach.

Objective: To investigate the occurrence of depressive and anxiety disorders in patients remitted for endovascular treatment of renal artery stenosis (RAS), and whether symptoms of depression and anxiety can be reduced after the treatment of RAS with percutaneous transluminal renal angioplasty (PTRA).Methods Patients: Selected for renal angiography with pressure measurement in the renal arteries due to suspected RAS were invited to participate in the study. 37 patients agreed to answer a questionnaire. Eighteen patients also agreed to a clinical psychiatric examination including the International Neuropsychiatric Interview (M.I.N.I. 6.0) to be diagnosed according to the DSM-IV. Results: Twenty-one of the 37 patients completing the questionnaire were found to have a pressure gradient of ≥ 10 mmHg at angiography, indicating significant stenosis. Ten of the 18 examined patients met the criteria for current DSM-IV anxiety diagnosis and two patients had a current depression. Three of the 18 examined patients had previously made a suicide attempt. Conclusion: The results of this study suggest that patients with suspected RAS have a high psychiatric comorbidity, as 56% of the patients undergoing psychiatric examination met the DSM-IV criteria for a current anxiety disorder.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, and caused coronavirus disease-19 (COVID-19), which is still a global pandemic. Dermatologic manifestations have increasingly been identified as significant extrapulmonary manifestations of COVID-19. The dermatologic manifestations associated with COVID-19 infection reported to date include maculopapular rash, vesicular lesions, urticaria-like lesions, and chilblain-like lesions. Knowledge of dermatologic manifestations of COVID-19 may be essential for early diagnosis and a better prognosis in COVID-19 patients. This review summarizes the current understanding of common COVID-19-associated dermatologic manifestations.

Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness

We describe an interesting case of Multi System Atrophy who had cross over features of progressive supranuclear palsy along with classical clinical findings which led to the diagnosis.

Introduction: Cancer treatment and prognosis depend heavily on early detection. Survival in the early stages is excellent for almost all types of cancer. Unfortunately, in Saudi Arabia, a large number of cancer patients present with advanced disease, resulting in a poor prognosis. There are three levels of delay in the management of cancer patients. The first level is the time between the first cancer-related symptoms and the presentation to the health facility, the second level is from the presentation to the diagnosis, and the third level is between the diagnosis and the treatment. This study aims to determine if there is a delay, at what level and to study the factors causing such delays.Materials and methods: Two hundred cancer patients who presented to the Armed Forces Hospital Southern Region, Oncology Department, were interviewed from January 1st to June 30th, 2018. The interviews were conducted by trained physicians familiar with the questionnaire’s contents. The questionnaire consisted of four sections: a demographic section and three more sections to identify factors causing the delay at the three levels from the patients’ perspectives. All data were analyzed using the SPSS version 20.0.Results: The mean patient age was 63 years. A total of 112 patients were female and 88 were male. The most common cancer type was breast cancer (27.5%). Among the patients, 61% were illiterate and 25.5% had elementary school degrees, 86% expressed little or no general medical knowledge about cancer. More women than men paid attention to cancer symptoms (70% vs. 54%). 75% of the patients presented to the first health facility after 2 months from the first appearance of symptoms (level 1 delay). Only 2% of the patients presented within one week. 50% of the patients received a diagnosis after visiting two health facilities. All patients were diagnosed at hospitals. 40% of patients used alternative medicines, 70% of whom thought this was the cause of their delayed presentations. 67% had their diagnosis confirmed within one month (level 2 delay), and 66% started their definitive treatment within one month (level 3 delay). 75% of the patients blame themselves for the delay. Educational level (p = 0.03), knowledge about cancer (p < 0.01), and the use of complementary and alternative medicines (CAM) (p = 0.01) were significantly associated with delayed presentation of patients to the health facility. Conclusion: There is a delay in the presentation of cancer patients (level 1) in the southern part of Saudi Arabia. Educational level, knowledge of cancer symptoms, and use of complementary and alternative medicines are the main causes. There were no delays in diagnosis and start of treatment (level 2,3).

There is a constant rise in cases of rhino-orbital mucormycosis in people with Coronavirus disease 2019 (COVID-19). Generally, Mucormycosis develops in immunosuppression or debilitating diseases. In cases having head and neck involvement, the mold enters the respiratory tract with further involvement of nose and sinuses and there is consecutive progression into orbital and intracranial structures. Diabetes Mellitus (DM) is an independent risk factor for both severe COVID-19 and mucormycosis. The clinical examination and direct smears are helpful for early diagnosis of the disease and timely intervention. For the better prevention and management of such opportunistic infections in COVID-19 patients, it is prudent to establish prophylactic treatment protocols along with rational use of corticosteroids. We here report a case of Rhino-orbital Mucormycosis infection caused by Rhizopus oryzae in a COVID-19 patient with Diabetes Mellitus.

Background: Relapsing polychondritis is a rare systemic disease characterized by recurrent inflammation, and often destruction, of cartilaginous tissues. Renal manifestations are rare. Membranous nephropathy complicating relapsing polychondritis has been reported only once previously, and there is no standardized treatment for membranous nephropathy associated with relapsing polychondritis.Case presentation: A 67-year-old Caucasian man with a history of chronic renal disease presented with 9 months of progressive dyspnea on exertion and 5 months of erythema, pain, and collapse of auricular cartilage. Imaging studies confirmed active inflammation of laryngeal, auricular, and costal cartilage and he was diagnosed with relapsing polychondritis.  Patient had longstanding proteinuria and renal biopsy demonstrated membranous nephropathy. Patient initially showed renal and respiratory improvement with etanercept, a tumor necrosis factor alpha inhibitor, treatment. However, subsequent disease and treatment-related complications led to a progressive overall clinical decline and patient died approximately 1 year following relapsing polychondritis diagnosis.Conclusion: Membranous nephropathy may rarely complicate relapsing polychondritis. In our case, both the cartilaginous inflammation and the renal disease improved after treatment with tumor necrosis factor alpha blockade, however complications of existing airway disease led to recurrent hospitalizations and eventually death.

Purpose: The sinusoidal obstruction syndrome (SOS) of the liver is an obliterative vasculitis that involves the terminal branches of the hepatic venules and sinusoids. When it is not treated, it will be a serious risk of mortality. Here, we aim to present our patient who has been associated with recurrent cholangitis attacks due to cholelithiasis and choledocholithiasis and is associated with sinusoidal obstruction syndrome with the literature.Description of the case: A 30 years old male patient had complaints of abdominal pain and nausea for a long time. The patient had a history of choledocholithiasis and cholangitis attacks. Although ERCP was performed and a stent was placed in the biliary tract, his jaundice did not disappear. Liver function tests were high. Tumor markers were negative.Methods: We could not make a definitive diagnosis with imaging methods and biopsy and we planned surgery. We performed segmental liver resection and biliary diversion in the surgery. Histopathological examination of the resected liver tissue was compatible with SOS.Conclusion: Many studies have been done on the etiology of SOS and different causes have been revealed. Accompanied with clinical findings, a definitive diagnosis is made with the exclusion of the presumptions considered. Surgery can be performed for both diagnostic and therapeutic purposes. If patients with elevated liver function tests and bilirubin have long-term abdominal pain, SOS should be bear in mind.

Background: Varied clinical manifestations, complex pathogenesis, and different viral serotypes make it difficult to predict the course of dengue disease. Many studies have been conducted on the prognostic factors for the occurrence of dengue shock syndrome (SSD), but all use the 2017 World Health Organization (WHO) guidelines. Aim: This study aims to determine the prognostic factors for the occurrence of SSD based on WHO guidelines in 2011. Method: Retrospective study using medical record data of pediatric patients aged 0 to <18 years with a diagnosis of dengue fever dengue (DHF), SSD, and expanded dengue syndrome (EDS) that meet WHO criteria in 2011 at the reputable database from 2017 to December 2020. Independent variables, namely gender, age, nutritional status, secondary dengue infection, leukopenia, abdominal pain, gastrointestinal bleeding, hepatomegaly, and plasma leakage. Shock is the dependent variable. Multivariate analysis using logistic regression analysis. Results: Subjects who met the study criteria were 145 patients, 52 (35.8%) of whom had SSD. Five of 52 SSD patients went into shock during hospitalization. The bivariate analysis yielded significant factors including, malnutrition, overnutrition and obesity, gastrointestinal bleeding, hemoconcentration, ascites, leukocytes 5,000 mm 3, encephalopathy, enzyme elevation heart, and overload. The results of multivariate analysis showed that hemoconcentration variables and elevated liver enzymes were factors of SSD Prognosis. Conclusion: Hemoconcentration and elevated liver enzymes are prognostic factors for SSD. 

Background: Dipylidium caninum, a zoonotic cyclophyllidean tapeworm, mainly infects dogs, cats, and occasionally humans as well. Here, we present D. caninum infection in a domestic cat. A cat of about one year of age with a history of intermittent diarrhea and shedding stool containing whitish cooked rice like soft particles. Methods: The case was identified by thorough clinical, coprological, and parasitological examinations, and treated accordingly.Results: During the physical examination, the cat was found to be infested with flea, and coprological investigation revealed the presence of gravid segments of cestodes. By preparing a permanent slide, we conducted a microscopic examination, and the cestode was confirmed as D. caninum. The cat was treated with albendazole and levamisole, which were ineffective; additionally, levamisole showed toxicity. Then, we administered niclosamide which completely cured the animal. On re-examination after a week, feces were found negative for eggs/gravid segments of any cestode. Conclusion: Niclosamide was found effective against dipylidiasis and can be treated similar infections in pets.

Background: Diabetic retinopathy (DR) is one of the most common causes of preventable blindness. Patients with Diabetes Mellitus (DM) develop not only DR but also corneal endothelial damage leading to anatomical and physiological changes in cornea. Central corneal thickness (CCT) is a key parameter of refractive surgery and Intraocular pressure (IOP) estimation. The role of CCT and higher glycemic index in DR needs to be researched upon.Objectives: To identify the corneal endothelial morphology in patients with type 2 DM, to measure the Central Corneal thickness (CCT) in patients with type 2 Diabetes Mellitus, to assess the relationship of CCT with HbA1C levels in the study group and to correlate the CCT with the severity of Diabetic retinopathy in the study group.Methods: A cross-sectional observational study was conducted between January 2018 and June 2019 in Vydehi Institute of Medical Sciences and Research Centre, Bangalore. The study included 100 subjects with type 2 DM for 5 years or more. Patients with comorbidities that may affect the severity of DR or alter CCT and other corneal endothelial parameters such as glaucoma, previous ocular surgery or trauma, corneal degenerations and dystrophies, chronic kidney disease and Hypertension were excluded. DR was assessed by dilated fundoscopy, fundus photography and optical coherence imaging of the macula and graded as per the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification. CCT and other corneal endothelial parameters were measured through specular microscopy. Relevant blood investigations including blood sugar levels were done for all patients.Statistical analysis: Relationship between CCT and grades of DR and HbA1c levels were established using the Chi-Square test. The level of significance was set at p < 0.05.Results: The mean CCT in patients with no diabetic retinopathy, very mild and mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe and very severe NPDR and PDR was 526.62 ± 8.084 μm, 542.07 ± 8.713 μm, 562.16 ± 8.255 μm, 582.79 ± 7.368 μm and 610.43 ± 18.256 μm respectively. Analysis of the relationship between CCT and severity of DR showed a statistically significant positive correlation between the two parameters (Pearson r = 0.933, p = 0.001). Beyond this, a correlation was found between all the corneal endothelial parameters and severity of DR. Multivariate analysis showed that advanced DR was positively correlated with CV (r  = 0.917) and CCT (r = 0.933); while it was negatively correlated with ECD (r = -0.872) and Hex (r = -0.811). A statistically significant correlation was also found between CCT and HbA1c. Also increasing age, duration of DM and higher glycemic index were positively correlated with severity of DR. Conclusion: This study, by demonstrating a strong correlation between the central corneal thickness to the severity of DR and HbA1c levels emphasizes the importance of evaluation of corneal endothelial morphology in the early screening and diagnosis of microvascular complications of DM.

Cancer, as a disease, has found a place in the social imaginary. Individuals construct ideas based on pre-established discourses—be they medical, media, or popular—which often hinder its prevention. Educational interventions have tended to focus on spreading information about the disease, ignoring its social connotations. The objective of the present study is to investigate the concept of cancer prevention in 980 adolescents, aged between 12 and 18 years, attending primary and secondary school in three public schools and one private school in the metropolitan region of São Paulo and the municipality of Dom Viçoso, Minas Gerais. The notion of prevention implies the dominant feeling of performing medical examinations from a symptom, against the idea of preventing, even when there is no clinical manifestation of the body. The majority of students emphasize the advantages of early diagnosis and that the decisive factor for the cure corresponds to the moment of detection: "cancer must be discovered in time". This is a solid belief within the body of knowledge about the disease that can be used as a starting point in prevention messages.However, even when the importance of early detection of cancer is understood as an essential element for its cure, care practices do not accompany the set of principles that regulate prevention or its demands.

Purpose: Real-time reverse-transcription polymerase chain reaction (RT-PCR)-based testing remains the gold standard for the diagnosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the high diagnosis demand of SARS-CoV-2 and the limited resources for RT-PCR testing, especially in Low-Income Countries (LICs), antigen-based methods are being considered as an option. The aim of this study was to assess the performance of LumiraDx SARS-CoV-2 antigen assay for large population screening compared to RT-PCR.Methods: This evaluation was conducted on 4146 participants including travelers and participants under household survey and vaccine evaluation studies before injection of the first dose. Oropharyngeal and nasopharyngeal swaps were collected from each participant into 2 mL of viral transport medium (VTM) and 400 μl of VTM were used to assess the performance of LumiraDx SARS-CoV-2 antigen assay, compared to RT-PCR. Results: The prevalence of SARS-CoV-2 of the cohort was 4.5% with RT-PCR and 4.1% with LumiraDx antigen test. Compared to the RT-PCR, the sensitivity and specificity of the LumiraDx antigen SARS-CoV-2 test were 82,7% [95% CI 74.1-89,7] and 99.9% [95% CI 99.6-99.9] respectively. Given the RT-PCR threshold cycle (Ct) range, the sensitivity was 92.1% [95% CI 84.6-96.3] when the Ct value was below or equal 33 cycles, and 38.1% [95% CI 18.9-61.3] when it was above 33 cycles. The inter-rater reliability showed a kappa coefficient of 0.88 when considering all the patients and 0.94 for Ct values below 33 cycles. Conclusion: Our data have shown that the LumiraDx platform can be considered for large-scale testing of SARS-CoV-2.

Background: Heparin-induced thrombocytopenia/thrombosis (HIT/T) is characterized by a fall in platelet count 5-10days after starting heparin therapy and is diagnosed with specific 4-T clinical features and laboratory tests. This complication is relatively common in Cardiothoracic surgery patients. Objective: To evaluate the positive and negative predictive value of various HIT laboratory tests and assess any correlation between HIT, the underlying diagnosis, underlying procedure, and mechanical cardiac devices. Patients and methods: The patient’s medical records were correlated with two laboratories HIT diagnostic tests, the pan-specific screening test with IgG, IgA, and IgM antibodies, followed by HIT specific IgG ELISA. Results: Total n = 80 patients were assessed, 48% (n = 38) were HIT screen pan-specific negative and 50% (n = 40) were HIT pan-specific positive and 2 cases were inconclusive. 17% (n = 14) were both pan-specific and specific HIT IgG ELISA positive. There were 5 atypical cases. One patient had Eosinophilic myocarditis and was HIT ELISA IgG neg. Argatroban was given on clinical grounds with successful recovery. One patient with Sarcoidosis had an aggressive course and received IV Immunoglobulin (IVIG) but succumbed secondary to liver failure. One patient progressed to gut ischemia and had surgical intervention but succumbed. Two patients with mechanical heart valves were on Argatroban but relapsed and responded to IVIG therapy. Conclusion: Our study indicates that 9/16 (> 50%) HIT-positive patients had valve replacement or cardiac devices suggesting that like knee arthroplasty there is a high incidence of HIT in patients with mechanical heart valves and cardiac devices and this warrants further prospective study.