Search

Objectives The 2019 novel coronavirus (2019-nCoV) has spread across the globe with more than 6 lakh deaths. Clinical autopsies are important to understand the pathobiology of the disease. Materials and Methods Autopsy techniques have been modified to be minimally invasive autopsies in all COVID-19 positive cases, and tissue biopsies were sampled from lungs, liver, and bone marrow within an hour after death. Detailed histological analysis was performed in the sampled tissues, along with immunohistochemistry. Patients’ clinical records were collected. Statistical Analysis Descriptive statistics were used to summarize data. Results Of the 21 cases studied, 76.2% patients were ≥ 60 years of age, 80.9% were males, and 85.7% had co-morbidities. Histopathological analysis revealed diffuse alveolar damage (including exudative and organizing phase) in 88.9% cases. Microthrombi were seen in 44.4% cases. Additional findings include viral cytopathic changes, metaplastic change in the epithelium, intra-alveolar hemorrhage, and pulmonary edema. Liver showed centrizonal congestion with hepatocytic loss, lobular inflammation, steatosis, Kupffer cell hypertrophy, and sinusoidal neutrophilic infiltration, while significant portal infiltrate and cholestasis were absent to minimal. Bone marrow revealed hemophagocytosis in 60% cases. Conclusion Incorporation of minimally invasive autopsies provides an effective method to study the pathological findings in COVID-19 deaths in resource-constrained settings. Presence of pulmonary microthrombi in a significant number of cases supports the vascular events, apart from the characteristic diffuse alveolar damage, as an important pathogenic mechanism for lung injury in COVID-19 infections. Histopathological findings in the liver and bone marrow suggest indirect insult to these organs, related to circulatory and/or hyperinflammatory response to viral infections.

Background The effect of individuals oral disease patterns on the family has been too little explored. Despite awareness of the importance of the family unit for personal health and health care system, the family unit has been infrequently studied from the public health point of view. Objective The specific aim of the study was to evaluate children's oral health as predictors of family functioning and to validate psychometric properties of Hindi version of family impact scale among 12-15-year-olds. Material and methods A total of 225 parent-child pair participated in the study. A cross-cultural translation, adaptation and validation of Hindi version of family impact scale (FIS) was conducted. Test-retest reliability was assessed by the intraclass correlation coefficients (ICC) using a two-way mixed-effect model. Discriminant validity was verified by family impact scores among parent-child pair with and without oral diseases. Construct validity was corroborated by association between the scale scores with global indicators of oral health and overall well-being. Clinical examinations were conducted using modified WHO criteria (1997). Influence of independent variables on the FIS were assessed using regression analysis. Results Mean impact score was 25.16 ± 5.96 with almost non-existent floor effect (4%) and no ceiling effect in the population. Inter Class Correlation for FIS scale was 0.86 indicating perfect agreement. Parents of children with dental caries and poor oral hygiene reported higher overall FIS scores (p Conclusions This study provides evidence that oral disorders have a significant impact on family functioning. The Hindi version of the FIS exhibited good psychometric properties, with acceptable validity and reliability. Future research needs to explore the consequences of higher family impact scores and focus on strategies to reduce the impacts of oral conditions on the family.

β-Thalassaemia, the most common monogenic disorder, is characterized by genetic heterogeneity at the molecular level. More than 300 mutations of the β globin gene have been characterized all over the world, however, few common mutations account for majority of the cases in various populations. The present study aimed to screen known cases of β-thalassaemia in the Western part of Rajasthan state for five common mutations. The study included 144 known cases of β-thalassaemia of all clinical phenotypes. Cases were diagnosed based on clinical features, haematology investigations including haemogram and Hb-HPLC. Blood samples from cases were taken for mutation analysis. After DNA extraction, mutations were characterized by the polymerase chain reaction method employing allele specific priming technique (AMRS) to study the five mutations including IVS-I-5 (G → C), IVS-I-1 (G → T), CD41/42 (–TCTT), CD 8/9 (+G) and 619 bp deletion from the 3′ end of the β-globin gene using a total of seven different primers. Of all 144 cases, 74 (51.38% of all) cases were of β-thalassaemia major, five (3.4% of all) cases were of β-thalassaemia intermedia and 65 (45.14% of all) cases were of β-thalassaemia minor. Mutation analysis revealed that five common mutations were present in 130 (90.27% of all) cases. Among identified mutations, highest frequency of mutation was of IVS-I-5 (G → C) identified in 73 cases (50.7% of all cases). In 11 (7.63% of all) cases, more than one mutation was identified. β-Thalassaemias are common in Western Rajasthan; however, there is dearth of literature from this part of the country. We observed that five common mutations are common in this part of the country also. These observations are helping us in forming the basis for comprehensive diagnostic database that would not only be useful for genetic counselling but also for prenatal diagnosis.

BackgroundAccurate diagnosis of anemia by community workers using a point-of-care device is a challenge. The objective of the study was to establish the diagnostic accuracy of point-of-care devices for detecting anemia in community settings.MethodsIt was diagnostic accuracy study with cross-sectional design on adult patients attending the outpatient department of rural/ urban health centres of Medical colleges from India. The index tests were HemoCue, TrueHb, Massimo’s device and spectroscopic device, compared against autoanalyzer (gold standard). Accuracy was expressed by sensitivity, specificity, likelihood ratios, predictive values, area under the curve (AUC) and levels of agreement. For the diagnostic accuracy component, 1407 participants were recruited with a minimum of 600 for each device. An additional 200 participants were considered to elucidate the performance of devices in different weather conditions.ResultsHemoCue and TrueHb performed better than Massimo and spectroscopic devices. Detection of anemia by technicians was similar between TrueHb and HemoCue (AUC 0.92 v/s 0.90,p > 0.05). Community workers performed better with Hemocue for detecting anemia compared to TrueHb (AUC 0.92 v/s 0.90,p p p HemoCue showed a bias or mean difference (95%CI) of 0.47 g/dl (0.42, 0.52) for all values, and 0.92 g/dl (0.82, 1.03) for severe anemia. For TrueHb, it was − 0.28 g/dl (− 0.37, − 0.20) for all readings, and 0.06 g/dl (− 0.52, 0.63) for severe anemia. TrueHb appeared to be more consistent across different weather conditions, although it overestimated Hb in extreme cold weather conditions.ConclusionFor detection of anemia, True Hb and HemoCue were comparable. For severe anemia, True Hb seemed to be a better and feasible point-of-care device for detecting anemia in the community settings.

Tuberculosis (TB) is an important public health problem in developing countries. In India, despite substantial efforts targeting TB and its associated risk factors, the number of cases remains high with 2.7 million new cases per year with a minimum 10% case contributed by paediatric TB. Disseminated TB has been increasingly recognised in children in recent times due to the increased prevalence of immune suppression secondary to AIDS and immunosuppressive therapies for various medical disorders and increasing awareness. Here we describe a 5-year-old girl who presented with fever of unknown cause, and her diagnosis of disseminated TB was delayed due to atypical presentation and the paucibacillary nature of paediatric TB. It was a bone marrow examination report which led us to clinch the diagnosis. The case highlights the difficulty in diagnosing disseminated TB and the importance of bone marrow examination in such cases.

Creutzfeldt–Jakob disease (CJD) is a well-described disease. It is characterized by rapidly progressive dementia, myoclonus, ataxia, pyramidal, and extrapyramidal signs. There are well-defined electroencephalogram and magnetic resonance imaging (MRI) findings, and markers found in the cerebrospinal fluid (CSF). The gold standard for diagnosing CJD remains brain biopsy. We present a case of a patient with a family history of biopsy-proven CJD who initially presented with symptoms of peripheral neuropathy. A month later, he developed ataxia, ophthalmoparesis, and then dysarthria. His initial workup was relatively unrevealing, showing an elevated protein in his CSF. He was thought to have Miller Fisher syndrome variant of Guillain–Barré syndrome. He neither, however, responded to plasmapheresis nor IVIG. He later started to develop progressive dementia. Repeated MRI showed restricted diffusion in the caudate and putamen, as well as in the cortex (cortical ribboning). Lumbar puncture was then found to be positive for 14-3-3 protein, total-tau protein, and real-time quaking-induced conversion assay, which are highly suggestive of CJD. We present a case of CJD with an unusual presentation resulting in misdiagnosis, prolonged workup, and potentially harmful treatment modalities. This case highlights the importance of broadening our definition of CJD to encompass more cases with unusual presentations.

Antiphospholipid syndrome (APS), an autoantibody mediated disease, is characterized by presence of antibodies against the proteins bound to the phospholipid membranes. The antibodies are predominantly formed against beta-2-glycoprotein I (b2GPI) which is considered pathogenic, but presence of lupus anticoagulant is a predictor of thrombotic events. The thrombotic events in APS may manifest as venous or arterial or small vessel thrombosis in any tissue or organ and pregnancy related complications namely, recurrent (three or more) and early spontaneous miscarriages before 10 weeks of gestation or unexplained deaths of normal fetus at or beyond 10 weeks, eclampsia or severe pre-eclampsia, intra-uterine growth retardation and pre-term births. However, lately its role as an etiological mechanism in causation of certain neuro-psychiatric disorders has been put forth. It has been suggested that one should suspect APS in psychiatric manifestations which are atypical, resistant to treatment, associated with cognitive decline and dementia, abnormal involuntary movements, livedo reticularis, migraine, thrombotic events like stroke or transient ischemic attacks, obstetrical complications. In this brief communication, we describe the case of young male who has been suffering from treatment resistant and difficult to manage bipolar affective disorder (BPAD) with fluctuating thrombocytopenia and neurological findings with positive lupus anticoagulant. We propose it to be a consequence of an atypical presentation of APS.

We report the case of an 84-year-old female presented to us with acute onset altered sensorium. On investigation, neurological and infectious causes were ruled out. On further evaluation, her serum calcium was found elevated (15.07 gm/dl). The diagnosis of hypercalcemic encephalopathy was made with the possibility of multiple myeloma due to raised total protein and globulin levels. Serum electrophoresis, immunofixation, and bone marrow examination confirmed the diagnosis of multiple myeloma. The patient was treated with bortezomib, dexamethasone, and lenalidomide. After 1 week, she improved with normalization of serum calcium. Herein, we highlight hypercalcemia as an important cause of encephalopathy. As our report suggests, metabolic encephalopathy can be the first presentation in multiple myeloma.

Objective Using video-EEG (v-EEG) diagnosis as a gold standard, we assessed the predictive diagnostic value of home videos of spells with or without additional limited demographic data in US veterans referred for evaluation of epilepsy. Veterans, in particular, stand to benefit from improved diagnostic tools given higher rates of PNES and limited accessibility to care. Methods This was a prospective, blinded diagnostic accuracy study in adults conducted at the Houston VA Medical Center from 12/2015–06/2019. Patients with a definitive diagnosis of epileptic seizures (ES), psychogenic nonepileptic seizures (PNES), or physiologic nonepileptic events (PhysNEE) from v-EEG monitoring were asked to submit home videos. Four board-certified epileptologists blinded to the original diagnosis formulated a diagnostic impression based upon the home video review alone and video plus limited demographic data. Results Fifty patients (30 males; mean age 47.7 years) submitted home videos. Of these, 14 had ES, 33 had PNES, and three had PhysNEE diagnosed by v-EEG. The diagnostic accuracy by video alone was 88.0%, with a sensitivity of 83.9% and specificity of 89.6%. Providing raters with basic patient demographic information in addition to the home videos did not significantly improve diagnostic accuracy when comparing to reviewing the videos alone. Inter-rater agreement between four raters based on video was moderate with both videos alone (kappa = 0.59) and video plus limited demographic data (kappa = 0.60). Significance This study demonstrated that home videos of paroxysmal events could be an important tool in reliably diagnosing ES vs. PNES in veterans referred for evaluation of epilepsy when interpreted by experts. A moderate inter-rater reliability was observed in this study.

Bone marrow microenvironment plays a crucial role in the growth of hemopoietic cells and bone marrow function, which in turn depends on an intact microvasculature. Our study assesses the microvessel density (MVD) in the bone marrow of aplastic anemia (AA) patients, compares with MVD of controls and MVD among the different types of AA. Bone marrow specimens from 60 patients with AA and 17 controls were studied. There were 33 patients with non severe AA (NSAA), 12 patients with severe AA (SAA) and 15 patients with very severe AA (VSAA). MVD was calculated on sections stained immunohistochemically for CD34. The mean bone marrow MVD in AA group was 1.28 ± 0.36, being significantly lower than that in control group (6.80 ± 1.59, p

Brucellosis is a common zoonotic disease worldwide. It has protean clinical manifestation and sometimes may has a life-threatening complication. A 4-year-old boy presented with a history of fever, myalgia and appetite loss for 3 weeks. On examination, he had hepatosplenomegaly. The initial working diagnosis was an infection, autoimmune disease and malignancy. Investigations showed positive Brucella serology, and he was started on rifampicin and cotrimoxazole. He was further investigated because of persistent fever, which revealed evidence of haemophagocytic lymphohistiocytosis (HLH). He continued treatment for brucellosis, except rifampicin which was replaced with doxycyclin due to a worsening liver function. The child showed complete clinical and biochemical improvement after 6 weeks of therapy. HLH is a life-threatening condition and should be suspected in children with brucellosis, who did not respond to appropriate antibiotics treatment. Secondary HLH does not always require specific therapy; it may improve with adequate treatment of the underlying condition.

We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed thrombocytosis, leucocytosis and peripheral blood smear showed a leucoerythroblastic picture. JAK 2 mutation was positive. To confirm the diagnosis of myeloproliferative neoplasm, bone marrow biopsy was done, which was suggestive of primary myelofibrosis. The patient underwent kidney biopsy due to rapidly declining renal function and persistent proteinuria, which was suggestive of focal segmental glomerulosclerosis. Early glomerulopathy is rare in myeloproliferative neoplasm, and aggressive follow-up is required to prevent progression of kidney disease.

Aplastic anemia (AA) is a life-threatening bone marrow failure disorder, if untreated, is associated with very high mortality. Allogenic bone marrow transplantation (BMT) is the standard of care for severe aplastic anemia (SAA) patients those who are younger than 40 years of age. The development of secondary malignancies in post-BMT setting for AA is a rare, however, well documented phenomenon. Among the secondary malignancies, development of acute myeloid leukemia is even rarer entity. Here we report a case of acute myeloid leukemia following human leucocyte antigen (HLA) matched sibling peripheral blood stem cell transplant (PBSCT) in a case of SAA. The patient achieved complete remission (CR) following chemotherapy and in CR1, a second HLA matched PBSCT from a different donor was offered. The patient is presently in remission at day +180 post-PBSCT.

Dear editor, Priapism, that is, persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation, is a relatively uncommon disorder and is a medical emergency. Typically, only the corpora cavernosa are affected [1]. The term priapism was derived from the Greek god Priapus, son of Aphrodite who was born with oversized genitals [2]. The haematological causes for priapism include Sickle cell anaemia, Leukaemia, Multiple myeloma, Paroxysmal nocturnal haemoglobinuria, Thalassaemia, Thrombocythemia and Henoch–Schonlein purpura [3]. As far as hemoglobinopathies are concerned, priapism is most often encountered in sickle cell disease in 38–42 % of cases followed by sickle/beta thalassemia [4, 5]. Priapism is also noted in patients with sickle cell trait even though the incidence is low as compared with sickle cell anaemia [6–9]. However, so far priapism in Hb E homozygosity is not reported in literature. In this correspondence we intend to bring to notice an unusual association of priapism with Hb E homozygosity. A 27 years old male, resident of North Eastern part of India was referred to our haematology OPD to rule out any underlying haematological disorder as the individual had an episode of priapism 3 months ago. The patient had an episode of unprovoked painful persistent erection for more than 8 h for which he sought medical advice. The surgeon at that medical center had managed with therapeutic needle aspiration from corpora cavernosa combined with flushing of cavernosa with normal saline to clear the sludged blood. The patient’s symptom subsided subsequently with the intervention and was referred to our center for further evaluation. On detailed clinical history, the individual was not on any medication for chronic illnesses; neither was he abusing any psychoactive drugs, alcohol, no history of prior trauma to the perineal region. His physical examination revealed mild pallor. There was no hepatosplenomegaly or lymphadenopathy. Systemic examination did not reveal any abnormality. On USG abdomen, spleen was not reported as enlarged (Span 13 cms). On investigations, haemoglobin, total leucocyte count and platelet count were 9.1 gm/dL, 7.1 9 10/lL and 118 9 10/lL respectively. Peripheral smear examination revealed microcytic hypochromic red cells and target cells with normal differential leucocyte count and reticulocyte count of one percent. There were no sickle cells or atypical cells in peripheral smear and sickling test was also negative. Subsequently Hb HPLC was performed which revealed with Hb A2 ? E of 92.6 % (Retention time3.68 min), Hb A of 6 % (Retention time 2.29 min) and Hb F (Retention time 1.06 min) of 1.6 % (Fig. 1; Table 1). This was followed by parental study which revealed Hb A2 ? E in mother and father of 29 and 27 % respectively suggestive of both parents being heterozygous for Hb E, S. Venkatesan A. Purohit (&) M. Aggarwal P. K. Singh T. Seth H. P. Pati Department of Hematology, All India Institute of Medical Sciences, New Delhi, India e-mail: purohitabhi80@gmail.com

Background: Bleeding is a common clinical presentation. Even patients with mild bleeding disorders are extensively investigated for ascertaining the cause. The present study was conducted in order to evaluate the extent of the possibility of diagnosis in mild bleeding disorders. Material and Methods: This was a prospective study of patients referred for work up of mild bleeding for a period of 13 months. A complete blood count, peripheral smear examination, Prothrombin time, Partial Thromboplastin time and Thrombin Time, Platelet Aggregometry test, tests for von Willebrand’s disease and Platelet function 3 availability were measured. Results: 164 patients presented with mild bleeding, in 114 of the patients a single site of bleeding was present. Epistaxis was the most common presentation (39%). Cutaneous bleeding (petechiae and purpura) was the next common site. History of a major bleeding tendency in the family was present only in 11 patients. The investigations showed that VWD (17/164), followed by clotting disorders (CD) mainly mild hemophilia (15/164) were the most common diagnosable cause. There were also 4 cases of hypofibrinogenemia. The disorders of platelets (Platelet function defects/PFD) were the least common (9/164). Rest 123 (75%) patients could not be diagnosed on the basis of these investigations and were labeled as Bleeding disorders – Unclassified (BDC). Conclusion: n our study, 75% of the patients with mild bleeding remained undiagnosed even after extensive laboratory workup, thus raising a very pertinent question that is it necessary that all mild bleeders submit to a broad battery of investigations, as the diagnosis continues to be elusive despite extensive workup.

Diagnosis of immune thrombocytopenia (ITP) is based on clinical suspicion and normal peripheral smear except for thrombocytopenia. Bone marrow examination is carried out to rule out leukemia, myelodysplastic syndrome or aplastic anemia. However, in most cases, clinical diagnosis is not altered after the bone marrow reports. Hence, this present study was carried out to evaluate the justification for bone marrow examination in the setting of isolated thrombocytopenia. All patients presenting to the hematology OPD with isolated thrombocytopenia and suspected diagnosis of ITP, between October 2011 and April 2013, were included in the study. Data was collected from bone marrow reports and outpatient records. A total of 353 cases were found. 319 cases had features of typical ITP and the rest had some form of organomegaly and/or lymphadenopathy. Bone marrow examination in all cases revealed normal hematopoietic elements and prominence of megakaryocytes including juvenile forms with no novel diagnosis in any patient. Routine use of bone marrow examination in the diagnostic workup of isolated thrombocytopenia is not required in our center even if steroids are planned as a first line therapy. However, a detailed history, thorough examination with complete hemogram and peripheral smear examination are essential.