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Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.

Studies have shown elevated levels of certain coagulation factors as risk factors for venous thromboembolism (VTE). In this study, we investigated the levels of coagulation factor VIII (FVIII), FIX and FXI in north Indian patients with VTE. A total of 123 patients with VTE were screened prospectively for FVIII, FIX and FXI levels and the conventional risk factors - deficiencies of protein C, S and antithrombin, positivity for antiphospholipid antibodies and the factor V Leiden mutation. Age-matched and sex-matched controls were included. VTE was secondary to known circumstantial and thrombophilic risk factors in 66 (53.7%) patients. In 46.3% (idiopathic VTE) patients, no cause was identified. The mean FVIII levels in idiopathic (187 IU/dl) and secondary VTE patients (185.4 IU/dl) were significantly higher compared with controls (129.6 IU/dl; P < 0.001). However, there was no statistically significant difference in the levels of FIX and FXI between patients and controls (P = 0.214 and 0.198, respectively). Patients with elevated FVIII levels had increased risk of VTE compared with controls (odds ratio: 9.4, 95% confidence interval: 4.7-18.79). On logistic regression analysis after adjusting for surgery and presence of antiphospholipid antibodies, this risk remained unchanged (odds ratio: 9.54, 95% confidence interval: 4.68-19.44). A dose-response relationship was observed with progressive increase in FVIII levels. Elevated FVIII levels constitute an independent risk factor for VTE in the north Indian population. Elevated levels of FIX and FXI were not associated with increased risk of VTE.

Aim The aim of this study was to evaluate the prevalence of mild cognitive impairment (MCI) in patients with hypertension and to evaluate the association of MCI with metabolic syndrome (MetS). Methodology 186 subjects with hypertension were evaluated on Montreal Cognitive Assessment (MoCA) and Patient Health Questionnaire (PHQ-9) for cognitive decline and depression, respectively and MetS was diagnosed as per the Consensus definition. Results The prevalence of MCI was 65.6 % and that of MetS was 45.7 %. Compared to those without MetS, those with MetS had significantly poorer cognitive functioning on the all cognitive domain of the MoCA, even after controlling for age, education, severity of the depression and duration of illness. Low High-Density Lipoprotein (HDL) was found to have a positive correlation with MoCA. Higher age, lower education, higher duration of illness and use of higher numbers of medications were associated with significantly lower score on MoCA. Conclusion Presence of MetS among persons with hypertension is associated with cognitive decline. Hence, there is a need to monitor and manage other parameters of MetS among patients with hypertension, to reduce the risk of cognitive decline and future dementia.

COVID-19 pandemic has emerged as a disaster for the human beings. All the Governments across the globe have been preparing to deal with this medical emergency, which is known to be associated with mortality in about 5% of the sufferers. Gradually, it is seen that, many patients with COVID-19 infection have mild symptoms or are asymptomatic. Due to the risk of infecting others, persons with COVID-19 infection are kept in isolation wards. Because of the isolation, the fear of death, and associated stigma, many patients with COVID-19 infection go through mental distress. In this report, we discuss the experience of 3 persons diagnosed with COVId-19 infection and admitted to the COVID ward.

Background & objectives: In India, spotted fever group rickettsiae (SFGR) are an underdiagnosed cause of acute febrile illness (AFI). The non-specific Weil-Felix test is the first diagnostic modality for the diagnosis of SFGR in many laboratories due to the lack of advanced diagnostic facilities in developing countries. The aim of this study was to detect SFGR using molecular methods in the patients, presenting with AFI in a tertiary care centre in north India. Methods: Consecutive patients (>14 yr of age) with AFI were enrolled over a six month period. Standard investigations for common pathogens causing AFI in India (malaria, dengue, scrub typhus, leptospirosis and enteric fever) were carried out. In patients who were negative for all of the above investigations, blood was subjected to polymerase chain reaction (PCR) targeting outer membrane protein A (ompA) gene of Rickettsia. Results: Of the 51 patients with an undiagnosed aetiology, three were positive by ompA PCR. Two of the PCR products produced good sequences and BLAST identification confirmed them as Rickettsia conorii. The sequences of R. conorii reported from south India clustered with two previously reported novel rickettsial genotypes. The study sequences clustered in a group different from that of Rickettsia spp. of the south Indian sequences reported earlier. Interpretation & conclusions: This study showed the existence of R. conorii in north India. Testing for SFGR may be included in the diagnostic workup of AFI for better disease management.

Scrub typhus caused by Orientia tsutsugamushi presents as an acute febrile illness with a varied presentation from mild illness to fatal disease in the absence of appropriate antibiotic treatment. Performing polymerase chain reaction (PCR) on eschar sample acts a rapid diagnostic tool in the early stage of scrub typhus when blood is negative. A total of eight patients from whom both whole blood and eschar samples were collected and tested by nested PCR targeting 56 kDa trichostatin A (TSA) gene to detect O. tsutsugamushi DNA. All (100%) eschar samples and three whole blood samples tested positive. Genetic analysis of the 56 kDa TSA gene sequences showed that the majority were related to Karp reference strains, while one clustered with Kawasaki strain. When present, eschar should be favoured as a diagnostic sample over whole blood in the early phase of infection.

Introduction Deep vein thrombosis is a multifactorial disease with many acquired and genetic risk factors. Polymorphism in the APOE gene is an upcoming potential pathogenic factor whose role is unclear in deep vein thrombosis. Methods An equal number of deep vein thrombosis cases and controls (N = 100, each) were investigated for APOE gene polymorphisms along with known acquired and hereditable thrombophilic risk factors. APOE genotyping was done by polymerase chain reaction. Results The ε3/ε4 and ε2/ε3 APOE genotypes were commoner in deep vein thrombosis cases than controls but not statistically significant ( ε3/ε4 → 18% versus 11%, OR = 1.776, CI = 0.792–3.984, p = 0.16; ε2/ε3 →10% versus 9%, OR = 1.123, CI = 0.436–2.895, p = 0.809). However, the following risk factors were found to be laterally associated with APOE genotypes in cases of deep vein thrombosis: pregnancy with ε2/ε3 genotype positivity (N = 29; p = 0.019), recurrent pregnancy loss with ε3/ε3 genotype (N = 29; p = 0.016), normal antithrombin levels with ε3/ε3 genotype (N = 62; p = 0.03) and non-O blood group with ε3/ε4 genotype (N = 100; p = 0.023). Conclusion APOE genotypes have shown only a modest association with deep vein thrombosis and were not statistically significant. A lateral association of these genotypes with thrombophilic risk factors was observed which may be investigated further for the possible pathogenetic mechanisms and their therapeutic implications.

Background To study the clinical profile and outcome of adult patients presenting with Scrub typhus ARDS in emergency at our institute. Methods Prospective observational study which included 126 adult patients presenting to emergency department at, PGIMER Chandigarh, a tertiary care referral institute in northwestern India with acute febrile illness with ARDS (acute onset respiratory distress within one week of fever or new/worsening respiratory symptoms with PaO2/FiO2 ratio less than 300 with PEEP or CPAP more than 5 cm H2O from January 2016 to December 2017.All the patients consenting for the study underwent detailed clinical evaluation and investigated for the etiology as per standard protocol followed at our institute with special emphasis to rule out tropical illnesses like scrub typhus, malaria, leptospirosis, dengue and H1N1 influenza. Patients were followed till discharge. Results Out of 126 patients eligible for the study, 45.2% were males and 54.8% were females. 47.6% were admitted in the monsoon/post-monsoon period. In addition to fever and dyspnea, cough (75.8%), hepatomegaly (56%), myalgia (63%), splenomegaly (31.3%), pedal edema (34.2%), pallor (40.4%), and vomiting (48.4%) were the common symptoms observed. Scrub typhus in 33.3%, followed by H1N1 influenza in 15.8%, co-infections in 12.6%, leptospirosis in (4.76%), dengue in (3.96%) and malaria in 3.17% of the patients, were the most common etiologies encountered. In 26.9% patients, no definite infective etiology could be found. Among the scrub typhus patients, 16 required ventilation. SOFA score of more than 6 was noted in 24 (57.14%) patients with scrub typhus as compared 9 (47.3%) patients with H1N1 infection. 12.1% of patients with scrub typhus succumbed to their illness when compared with 36.8% of patients with H1N1 infection. At admission in emergency female sex (P = 0.048), age less than 45 years, (P = 0.020), abdominal pain (P = 0.011), presence of hepatosplenomegaly (P = 0.001/0.010), thrombocytopenia Conclusion Scrub typhus is an important, treatable tropical infection causing ARDS especially in monsoon/post-monsoon seasons in Northwestern India. Disclosures All authors: No reported disclosures.

There is controversy about whether 3- or 6-month molecular assessment predicts progression-free and overall survival in those with chronic myeloid leukemia (CML). The factors predicting molecular response at 3, 6, and 12 months have not been studied extensively. The study objective was to study the factors affecting molecular response at 3 and 6 months in patients with CML who are receiving imatinib mesylate.We prospectively enrolled patients with newly diagnosed CML who were receiving imatinib mesylate as the initial therapy for CML. The diagnosis of CML was based on clinical examination, bone marrow, and demonstration of BCR ABL(IS) transcripts by polymerase chain reaction. The molecular response(IS) was assessed at 3, 6, and 12 months by GeneXpert (Cepheid, Sunnyvale, CA) and co-related with various baseline characteristics of patients. We also looked at whether early achievement of a complete hematologic response within 6 weeks predicts molecular response at 3 or 6 months. The study took place at a tertiary care hospital in Northwest India catering to patients belonging to low-middle socioeconomic status.We enrolled 131 patients with CML in the chronic phase from July 1, 2013, to August 31, 2014. The median age of the patients was 40 years (range, 13-67) with a male preponderance (61% were male). Most patients presented with symptoms of low-grade fever (52.7%) and abdominal fullness (26.7%). Spleen was palpable in 84.7% of patients. The median hemoglobin at presentation was 10.8 g/dL (range, 4.8-18.4 g/dL), white cell count was 138.3 × 10(9)/L (4.1-697 × 10(9)/L), and platelet count was 326 × 10(9)/L (85-1819 × 10(9)/L). The median number of peripheral blood basophils was 3% (range, 0%-20%), and blasts were 3% (range, 0%-10%). Myelofibrosis of more than grade 1 was present in 30% of patients. Most patients belonged to intermediate Sokal (45.8%) and Hasford (55%) scores and low EUropean Treatment Outcome Study (78.6%) score. Of 128 evaluable patients at 3 months, 96.9% achieved complete hematologic remission (CHR) and 82.3% achieved BCR ABL(IS) of less than 10%. None of the patients who had BCR ABL(IS)10% at 3 months achieved BCR ABL(IS)1% at 6 months or0.1% at 12 months. Early achievement of CHR (6 weeks), peripheral blood blast count of5%, and lactate dehydrogenase851 U/L were significantly associated with achievement of BCR ABL(IS)10% at 3 months and BCR ABL(IS)1% at 6 months.We found that BCR ABL(IS) assessment at 3 months is superior to assessment at 6 months. Patients with CML in the chronic phase who achieve CHR within 6 weeks are more likely to achieve BCR ABL(IS)10% at 3 months and1% at 6 months than patients who achieve CHR between 7 and 12 weeks.

Patients with acute leukemia (AL) are predisposed to develop infections including tuberculosis (TB). The risk is specifically higher in patients from TB endemic areas. Patients (≥12 years) with AL treated between January-2014 to January-2017 who developed TB were reviewed. Patients were classified into three groups: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APML) and a systematic analysis of clinical features and outcomes was conducted. Over the study period, 26 patients of AL developed TB. The median time to diagnosis of TB was 8 weeks (0–432 weeks) following the diagnosis of AL and it was comparable between the three leukemia groups. The diagnosis of TB required alteration of anti-leukemia therapy in 26.9% patients and rescheduling in another 42.3% patients. Therapy alteration/rescheduling were more frequent in patients with AML as compared to ALL and APML (p

Objective Medically unexplained physical symptoms (MUPS) are commonly seen across health care settings. Earlier studies have focussed on prevalence, cost-utilization and burden. Data from India is scarce. Patients with persistent MUPS have more impairment and psychological distress. This study was designed to assess psychological morbidity, health anxiety (HA), somatic symptom load, disability, quality of life (QOL) in patients with persistent MUPS presenting to a general medical outpatient service and compare it with patients with medically explained physical symptoms (MEPS). Methods The study was conducted in the outpatient service of the Department of Internal Medicine in a tertiary hospital in North India. Persistent MUPS was defined as physical symptoms of at least 3 months duration leading to dysfunction and with no identifiable medical cause. 70 patients with persistent MUPS and MEPS each were recruited. Psychiatric morbidity was assessed using the Mini International Neuropsychiatric interview, somatic symptom load with Patient Health Questionniare-15 (PHQ-15), HA with Whiteley Index, disability with WHODAS 2.0 and QOL with WHOQOL-Bref. Results Both the groups were comparable on socio-demography and length of symptoms. Prevalence of psychiatric disorders and HA was significantly greater in MUPS. Patients with persistent MUPS had significantly more health care utilization, number and burden of somatic symptoms, greater disability and worse QOL. Conclusions Patients with persistent MUPS have a different profile when compared to MEPS. There is a need to screen and identify patients with MUPS and manage them keeping in mind the psychological factors and chronic nature and number of symptoms.

Background & objectives: Adriamycin though considered as an effective anticancer drug, leads to irreversible cardiomyopathy (CMP) and congestive heart failure (CHF). The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy (CMP) in cancer patients. Methods: Patients with lymphoreticular malignancy in whom ADR therapy was planned were randomized into two groups: carvedilol and control. Twenty seven patients each were enrolled in carvedilol and control groups. In the carvedilol group, 12.5 mg once daily oral carvedilol was given during six months. The patients were evaluated by echocardiography before and after chemotherapy. Left ventricular ejection fraction (EF) and systolic and diastolic diameters were calculated. Results: At six months of follow up, six patients in the carvedilol group and five in the control group had died. The mean EF (63.19 vs. 63.88%) and fraction shortening (FS) (34 vs. 34.6) of the carvedilol group were similar at follow up, but in the control group, the mean EF (67.27 vs. 60.82%, P =0.003) and FS (38.48 vs. 34.6, P

Objective: To evaluate the efficacy of a single intravenous (IV) dose of anti-D in severe thrombocytopenia (

Hypereosinophilia is part of a group of complex disorders with multisystem involvement. A 23 year old male was admitted to our centre with bilateral popliteal artery and venous thrombosis and impending gangrene of the left forefoot along with deep venous thrombosis of the right lower extremity. Investigations revealed marked peripheral blood eosinophilia (27,669/μL). Bone marrow showed increased eosinophils & eosinophil precursors and no evidence of a clonal disorder. Skin biopsy from the ulcerated lesions showed small vessel vasculitis with intense eosinophilic infiltration. Investigations to look for secondary causes of hypereosinophilia in the form of Antinuclear Antibody, P-Anti Neutrophil Cytoplasmic Antibody (ANCA) and C-ANCA and FIP1L1-PDGFRA, Bcr-Abl and JAK2V617F mutations were negative. The arterial and venous thrombosis and cutaneous vasculitis were linked to the presence of hypereosinophilic syndrome. The patient’s illness responded to high dose corticosteroids leading to complete resolution of symptoms. We reviewed the literature on the lesser known entity of eosinophilic vasculitis and its association with thrombosis.

Background: Family members are critical partners in the plan of care for patients both in the hospital and at home. Involving the members of the family in acute care can help the nursing staff in emergency. The present study was aimed to find out the role of the family members while caring for the patients admitted in emergency unit of a tertiary care hospital. Materials and Methods: A total of 400 family members of the patients were conveniently selected. Only one member per family was interviewed and their role in taking care of the patient in acute care setting was evaluated. Results: The mean age of patients admitted in acute care setting was 46.6 yrs ± 18.8 with the age range of 18-84 years. Majority (39%) of the patients were in the age group of 31-60 years. More than half of the caregivers of patients were males and 88% of them were first-degree relatives. The major tasks performed by the caregivers during the patient care was communicating with doctors/ nursing staff (98%), cleaning and dressing the patient (94%), feeding the patient (90%), procuring medication and other supplies (88%), administering oral medications (74%), changing position and helping for back care (65%), shifting the patients for investigations (60%), collecting reports (35%) and providing physiotherapy (25%). Conclusions: The results of the study concluded that family involvement in acute care setting can help the nursing staff in taking care of the patient in acute care setting and it also provides the opportunity for preparing them for after care of the patients at home following discharge.

Background To study the region-specific etiology and outcome in adult patients with acute febrile illness and ARDS Methods Prospective observational study done among 102 adult patients admitted to medical emergency, PGIMER, during study interval of 18 months (January 2016 to June 2017), with acute febrile illness (oral temperature more 101°F for less than 14 days with no localising symptoms) and ARDS(acute onset respiratory distress within one week of fever or new/worsening respiratory symptoms with bilateral opacities on chest radiograph, symptoms not explained by cardiac failure or fluid overload with PaO2/FiO2 ratio 5 cm H2O).All patients were investigated for the etiology as per standard protocol for malaria, scrub typhus, Leptospira, enteric fever, dengue, H1N1 influenza. Patients were followed till discharge or 28th day whichever is longer Results Among the 102 patients recruited in the study, 41.2% were males and 58.8% were females. Mean age of presentation was 38.06+/−17.26 years. 46% of patients admitted during post monsoon season. 26.5% patients had succumbed to their illness. Cough (61.8%), hepatomegaly (50%), myalgia (50%), splenomegaly (30.3%), pedal edema (31.4%), pallor (39.4%), vomiting (26.7%) were most common findings apart from fever and dyspnoea. Nine of them had bleeding manifestations. The most common diagnosis was Scrub typhus (32.4%), followed by coinfections (13.7%), H1N1 influenza in 8.8% cases. 30.4% patients did not fall into any diagnostic criteria. Leptospira, dengue and Malaria were present in 4.4 and 2 cases, respectively. A total of 50 patients were intubated and ventilated during their stay in the hospital. APACHE 2 score was observed to better predict mortality than SOFA score. Factors which predicted mortality were male sex, age >45 years, invasive ventilation and low GCS Conclusion Fever and ARDS have more incidence among young females and occur significantly during post monsoon season. Scrub typhus constituted the majority of fever with ARDS cases followed by H1N1. Coinfections were common cause of Fever with ARDS. Predictors of mortality were male gender, old age, long duration of invasive ventilation, higher serum procalcitonin levels and low GCS at admission. APACHE 2 score was a better predictor of mortality than SOFA score. Disclosures All authors: No reported disclosures.

Background: Geriatric anemia is a global health problem because of its high prevalence and associated significant morbidity and mortality. Aim: The objectives of this study were to estimate the pattern of anemia in the elderly patients and the underlying etiology of anemia. Research Design and Methods: This was a hospital-based prospective observational study, conducted in patients aged 60 years and above at PGIMER, Chandigarh, a tertiary care center of North India. Anemia is defined as hemoglobin level less than 13 g/dl in men and 12 g/dl in women. Results: Among the 105 older patients with anemia, the mean value of hemoglobin was 8.8 ± 2.3 g/dl. The etiological distribution of anemia was iron deficiency in 26 patients (24.8%), chronic disease in 24 patients (22.9%), hematological disorders in 21 (20%), chronic kidney disease in 13 (12.4%), multifactorial in 8 (7.6%), vitamin B12 deficiency in 2 (1.9%), folate deficiency in 1 (0.9%), and hypothyroidism in 1 patient (0.9%). No etiology could be found in 9 patients (8.6%). 57.6% of the iron-deficient patients had upper gastrointestinal lesions and 30.7% had a nutritional cause. Common chronic diseases causing anemia were malignancy (36.6%) and liver disease (29.1%). The myelodysplastic syndrome was the commonest hematological disorder. 53.35% of the patients had normocytic anemia, 40% had microcytic anemia, and 6.6% had macrocytic anemia. Conclusions: In most of the cases, anemia in the elderly had a treatable cause. Thus, a thorough investigation including gastrointestinal endoscopy is warranted. Unexplained progressive or unresponsive anemia requires bone marrow examination.

Classically, antiphospholipid antibody syndrome (APS) presents with recurrent episodes of vascular thrombosis and abortions. For APS to present as fever of unknown origin (FUO) is a rare phenomenon. We present an interesting case of FUO who on workup was found to have primary APS with right atrial thrombus and chronic pulmonary thromboembolism (PTE). Fever resolved completely with anticoagulation therapy and surgical removal of the intra-cardiac thrombus. Although rare, APS should be considered in any case of FUO with prolonged activated partial thromboplastin time and/or thrombocytopenia. We also take this opportunity to briefly review 28 cases of APS with intra-cardiac thrombus reported to date in the medical literature. .

A 15-year-old boy with night blindness since the age of six presented to the outpatient wing with a history of growth retardation, poor scholastic performance and failure to attain secondary sexual characters. Retinal imaging showed the presence of pigmentary retinal degeneration and attenuated vessels suggesting retinitis pigmentosa [Table/Fig-1]. Physical examination revealed dysmorphic facies [Table/Fig-2] - widened intercanthal distance, low set ears, depressed nasal bridge and a flattened occiput [Table/Fig-3]. Also truncal obesity [Table/Fig-3], shortened metacarpals/phalanges [Table/Fig-4], polydactyly [Table/Fig-5], and underdeveloped testes were noted. In view of the constellation of findings, a diagnosis of Bardet–Biedl Syndrome (BBS) was made. Nutritional supplementation was advised and the patient was referred for IQ assessment and genetic counseling. [Table/Fig-1]: Fundus photograph of the left eye demonstrating pigmentary changes and arteriolar attenuation characteristic of retinitis pigmentosa. [Table/Fig-2]: Dysmorphic face with depressed nasal bridge, widened intercanthal distance and low set ears. [Table/Fig-3]: Depicting the flattened occiput and trucal obesity. [Table/Fig-4]: Brachydactyly, shortened metacarpals and phalanges. [Table/Fig-5]: Postaxial polydactyly. In 1866, Laurence and Moon described four patients with retinal degeneration, obesity, and cognitive deficit [1]. Bardet and Biedl separately reported similarly affected individuals who also had postaxial polydactyly and the condition was coined Laurence– Moon–Bardet–Biedl syndrome [2,3]. The syndrome is often divided into two entities: Laurence–Moon syndrome and Bardet–Biedl Syndrome (BBS), but since there is considerable overlap, BBS is now the globally accepted name. Beales et al., proposed a modified criteria in 1999, requiring four primary features or three primary features with two secondary features for the diagnosis [4]. Rod-cone dystrophy, polydactyly, truncal obesity, genital anomalies, chronic kidney disease and learning disabilities form the primary features, while speech delay, developmental delay, diabetes, dental anomalies, congenital heart disease, brachydactyly/syndactyly, ataxia/poor coordination and anosmia/hyposmia are the secondary features. The diagnosis of BBS is delayed and considered only when the child develops visual problems associated with rod-cone dystrophy [5]. Postaxial polydactyly may be the only hint to the diagnosis at birth and hence its presence should alert physicians to look for other features of BBS [5]. Our patient had five primary and three secondary features. BBS is a rare and complex syndrome, autosomal recessively inherited, involving mutations of proteins that form components of the ciliary apparatus. But as emphasized by our patient, the diagnosis remains clinical. Treatment and rehabilitation involve a multidisciplinary approach. Early recognition and treatment of co-morbidities are imperative to improve the quality of life.

Bal A, Suri V, Mishra B, Bhalla A, Agarwal R, Abrol A, Ratho R K & Joshi K (2012) Histopathology 60, 326–335 Pathology and virology findings in cases of fatal influenza A H1N1 virus infection in 2009–2010 Aims: To describe the pathological findings, immunohistochemical localization of viral antigen and tissue reverse transcriptase polymerase chain reaction (RT-PCR) findings of different organs in cases of fatal H1N1 influenza virus infection from North India. Methods and results: Nine patients positive for H1N1 virus by a throat swab real-time RT-PCR (rRT-PCR) were included. Underlying risk factors included pregnancy, respiratory diseases, rheumatic heart disease, and chronic kidney disease. Pathological evidence of tracheitis, necrotizing bronchiolitis and diffuse alveolar damage was noted in all of the cases. Influenza viral antigen was observed by immunohistochemistry in the epithelium of the tracheobronchial tree, bronchial glands, gland ducts, and, less frequently, the alveolar epithelial cells. Viral particles were confirmed by electron microscopy in three autopsy cases. Tissue rRT-PCR for H1N1 viral RNA was positive in lung samples, but negative in other organs. Secondary bacterial pneumonia, cytomegalovirus infection and angio-invasive zygomycosis were detected. Conclusions: The pulmonary findings are similar to those described in past pandemics. Secondary fungal and viral infections, which have not been reported previously, were noted. Although the number of cases in this study is small, the findings reinforce the notion that changes in extrapulmonary organs are attributable to multiorgan dysfunction syndrome rather than a viral cytopathic effect, and that there is no transplacental transmission of virus.

A 22-year-old woman underwent normal vaginal delivery; 3 days later, she developed fever and rashes over all four limbs followed by decreased urine output. Examination revealed pedal oedema, non-palpable purpuric lesions over extremities with erosions at few places, and blackish discolouration of second and third toe of right foot (figure 1A). On investigation, haemoglobin was 6.7 g/dL, white blood cell 26 200/mm3, platelet 39 000/mm3, prothrombin time 25 s (control 12–14 s), activated thromboplastin time 38 s (control 24–30 s) and serum creatinine 9.1 mg/dL. Urine showed albumin 1+. Ultrasound was suggestive …

Background Central nervous system (CNS) involvement by Hodgkin lympboma is a rare event. Involvement of the cerebrospinal fluid (CSF) in such cases is even more uncommon. We report a case of Hodgkin lymphoma in which the patient developed infiltration of the CSF while on chemotherapy. Case A 45-year-old woman was diagnosed with Hodgkin lymphoma by fine needle aspiration and subsequent biopsy of the cervical lymph node. She complained of headache during the course of chemotherapy, for which CSF examination was undertaken. Cytocentrifuge sediment of the CSF revealed marked eosinophilic pleocytosis, accompanied by scattered monocytes, polymorpbs, lymphocytes, plasma cells and histiocytes. An occasional large mononudlear cell with a large, round nucleus and prominent irregular nucleolus with a moderate amount of basophilic cytoplasm conformning to the morphology of Hodgkin's cells was noted. Binucleated Reed-Sternberg cells were not seen. Following intratbecal methotrexate, a reduction in the cellular infiltrate was observed. Conclusion CSF cytology is important for the diagnosis of CNS involvement by Hodgkin lymphoma and may be positive before lesions can be visualized by magnetic resonance imaging or computed tomograpby scans.

Infectious diseases affect those who have limited access to care, but these diseases are no longer a cause of concern for the developing countries alone. Some exotic infections have already started appearing in the developed world, courtesy the AIDS epidemic. The possible misuse of these infectious agents for bioterrorism has further compounded the problem. These threats have forced developed countries to stand up and take notice of these neglected diseases. The collaborative efforts of the international agencies have started yielding some results, but there is still a long way to go. The biggest perceived threat is the patents on therapeutics for these diseases. This article has tried to access the global burden of infectious disease, the threat of patents on therapeutics as perceived by the developing countries and the ongoing international efforts in this regard. The authors also suggest some measures that may help overcome this threat of patents on therapeutics for neglected infectious disease.

Castleman’s disease (CD) is a heterogeneous lymphoproliferative disorder of unknown aetiology. Mostly, this disorder is seen in immunocompromised hosts. It is known to be associated with systemic disorders like HIV, HHV-8, lymphoma, and Kaposi sarcoma. As of today, the clinical behaviour and outcome of CD in immunocompetent host remains suboptimally studied. We analyzed consecutively treated cases of CD presented to our centre in last 12 years. Case record files were studied for patient’s characteristics, clinical presentation, baseline laboratory and pathologic parameters, therapy and outcome. This study describes presentation and treatment outcome of CD in immunocompetent patients. Total 16 patients of CD were treated during the study period. The median age of patients at the time of presentation was 40.5 years (range 13–72 years). An equal number of patients (8 each) had unicentric and multicentric CD. Sixty-three percent patients had hyaline vascular subtype while 37 % patients had plasma cell or mixed variant. Majority of the patients had good performance status (ECOG PS 0, 1 in 10 (62.5 %) patients; PS2-4 in 6 (37.5 %) patients). The median duration of symptoms was 6 months (range 2–36 months). None of the patients in our study had associated HIV infection. Six patients presented with fever, out of which four had plasma cell variant of CD and three of them had multicentric involvement. In comparison to unicentric CD, patients with multicentric CD had lower albumin levels (4.15 vs. 3.38 g/dl, p = 0.006), haemoglobin levels (11.3 vs. 9.8, p = 0.06), and lower complete remission rates (62.5 % vs. none). Patients were treated according to the stage and clinical status with surgery, chemotherapy or combination of both modalities. Surgery was the predominant treatment for unicentric CD while multicentric CD was treated with various chemotherapy regimens. Eight patients were treated with chemotherapy (CHOP-based regimen-5, melphalan-prednisolone thalidomide-1, chlorambucil-prednisolone-1, and only corticosteroids-1). In the entire study group, ORR was 72 % (CR 36 %, PR 36 %), one patient died of progressive disease during chemotherapy. Two patients lost to follow-up before assessment of treatment response. Five-year overall survival was 100 and 87 % for unicentric and multicentric CD respectively. Castleman’s disease is a rare lymphoproliferative disorder amongst Indian patients. It more commonly presents as hyaline vascular variant and affects middle-aged individuals. The most remarkable fact in our analysis was a lack of HIV positivity in any of the patient that is in contrast to the majority of the published literature. With multimodality therapy, high response rates and long-term survival were noted in the entire study group.

Myeloid sarcoma (MS) represents extra medullary accumulation of the immature cells of granulocytic series and occurs most commonly in the setting of acute myelogenous leukemia. Its occurrence in chronic myeloid leukemia (CML), myelodysplastic syndrome and other myeloproliferative neoplasm is uncommon. We here in report a 35-year old lady who was diagnosed as CML-chronic phase (CP) in the year 2004 and was on imatinib (400 mg OD) since then with regular follow up and good compliance. She had progression to accelerated phase in April 2014 which was managed by increasing the dose of imatinib to 600 mg OD. In August 2015, she presented with complaints of pain and swelling of the left shoulder suggestive of septic arthritis. Investigations revealed an ill-defined lesion involving muscles around the shoulder and clavicle. Absence of response to antibiotics and negative work up for infectious etiology raised the suspicion for MS which was later confirmed by immunohistochemistry of the aspirate from the lesion. Bone marrow examination was consistent with CML-CP. Hence, the diagnosis of CML with extra medullary blast crises was made. Patient was treated with a combination of high dose imatinib, hydroxyurea, cytarabine and local radiotherapy. Rarity of MS involving the shoulder and it's resemblance to septic arthritis has been highlighted in the present case. We emphasize the importance of immunohistochemistry of the aspirate for the timely and correct diagnosis of the cases who do not respond to an initial antibiotic trial.

Background Peripheral neuropathy (PN) is detected in up to 62% patients with multiple myeloma (MM) at diagnosis. No specific risk factor for pretreatment neuropathy has been identified. Patients and Methods We evaluated 29 sequential patients with MM attending our tertiary care center for peripheral neuropathy at diagnosis using symptoms, clinical examination, and nerve conduction studies (NCSs). Total Neuropathy Score, reduced (TNSr) and Total Neuropathy Score, clinical (TNSc) were calculated, and a score of ≥ 2 in each scale was considered diagnostic of PN. The study was approved by our institutional review board. Results We found that 51.7% (n = 15) and 17.2% (n = 5) of patients had pretreatment neuropathy by TNSr and TNSc scales, respectively. Higher glycated hemoglobin (HbA1C) ( P = .022), higher body mass index (BMI) ( P = .008), higher serum creatinine levels ( P = .023), and higher blood urea levels ( P = .006) were associated with neuropathy by TNSr in univariate analysis. Higher blood urea levels ( P = .023), higher serum creatinine levels ( P = .003), and higher serum β 2 -microglobulin levels ( P = .013) were associated with neuropathy by TNSc in univariate analysis. Higher HbA1c levels ( P = .036; odds ratio [OR], 9.46) and BMI ( P = .028; OR, 1.78) were associated with neuropathy by TNSr on binomial logistic regression analysis. Cutoffs of 5.6% (sensitivity, 60%; specificity, 71.4%) and 23.7 kg/m 2 (sensitivity, 80%; specificity, 71.4%) were obtained for HbA1c (area under the curve [AUC], 0.75) and BMI (AUC, 0.79), respectively, on receiver operating characteristic (ROC) curve analysis to predict neuropathy. The combination of HbA1c ≥ 5.6% and BMI ≥ 23.7 kg/m 2 had higher odds of neuropathy by TNSr (OR, 27.0; 95% confidence interval [CI], 2.0-368.4) when compared with either factor alone. Conclusion Use of TNSr, which incorporates electrophysiological abnormalities in addition to clinical manifestations, improves the detection rate of neuropathy. We found that high HbA1c and high BMI together are risk factors for neuropathy at diagnosis in patients with MM.

Rapidly changing field of genetic technology and its application in the management of hematological malignancies has brought significant improvement in treatment and outcome of these disorders. Today, genetics plays pivotal role in diagnosis and prognostication of most hematologic neoplasms. The utilization of genetic tests in deciding specific treatment of various hematologic malignancies as well as for evaluation of depth of treatment response is rapidly advancing. Therefore, it is imperative for practitioners working in the field of hemato-oncology to have sufficient understanding of the basic concepts of genetics in order to comprehend upcoming molecular research in this area and to translate the same for patient care.

Osler-Weber-Rendu disease (OWRD) is a rare vascular dysplasia that presents most commonly with epistaxis. The most dreaded complication, however, is an intracranial haemorrhage. We present a patient with two rare manifestations of OWRD, subdural haematoma and portal venous hypertension, both seldom reported in the literature. The patient made a full recovery and continues to do well at this time.

A-14-year old boy, presented with a short history of excessive thirst and increased urine output. Clinical examination showed pallor, generalized lymphadenopathy and hepatosplenomegaly. For evaluation of his polyuric state he underwent routine laboratory investigations, including renal function test, acid-base studies, urine analysis. Blood tests suggested hypokalemia, hypouricemia, hypocalcemia and hyperchloremia with normal liver and kidney function tests. The arterial blood gas analysis was suggestive of normal anion gap metabolic acidosis. Urine analysis was suggestive of hyperuricosuria, hypercalciuria and glycosuria with a positive urine anion gap. His hemogram showed pancytopenia with differential count showing 88% blasts. Bone marrow examination and flowcytometry confirmed the diagnosis of B cell acute lymphoblastic leukemia. Hence this case was atypical and very interesting in the sense that the Fanconi syndrome is very rare to be an initial presenting feature of acute lymphoblastic leukemia. The patient was started on oral as well intravenous supplementation with potassium, bicarbonate, calcium and phosphorus. Simultaneously, as per the modified BFM -90 protocol (four drug based regimen-Prednisolone, vincristine, daunorubicin, cyclophosphamide along with l-asparaginase), he was started on induction protocol. By the end of 3rd week of induction therapy, his urine output started normalizing and finally settled at the end of induction therapy. At present he is in the maintenance phase of chemotherapy.

Epstein-Barr virus (EBV) is the first herpes virus to be completely sequenced. It is implicated in diseases from the benign infectious mononucleosis to malignant nasopharyngeal carcinoma, Burkitt’s lymphoma and primary CNS lymphoma in AIDS patients. It has also been found to be associated with some miscellaneous diseases like chronic fatigue syndrome, multiple sclerosis etc. however causality still remains an issue of debate. As the virus mainly targets the lymphomononuclear cells and the reticuloendothelial system of the body, it’s various manifestations are often mistaken as leukemic malignancies. We report two such cases of young adults who had been diagnosed as having acute leukemia on the basis of atypical cells in the peripheral blood. One patient later turned out to be a classical infectious mononucleosis and second patient had EBV associated hemophagocytic lymphohistiocytosis syndrome.

We present a rare severe leptospirosis in a patient who presented with fever, jaundice, coagulopathy and intrauterine fetal demise. Possibility of leptospirosis should be kept in an obstetric patient with such clinical profile particularly in endemic areas or if there is recent outbreak of disease.

Treatment for hairy cell leukemia (HCL) has evolved over the years from splenectomy to interferon to purine analogs to monoclonal antibody based therapy [1]. Until three decades ago, splenectomy wa...

Methotrexate is an antimetabolite commonly used in clinical practice for a variety of indications ranging from rheumatoid arthritis and other connective tissue disorders to high dose regimens in many malignancies. This folate antagonist has got a spectrum of toxicities among which gastrointestinal effects predominate . Lung injury is a well described but rare event and has been reported most often in patients who have been on long term oral therapy for rheumatic disorders. Acute lung injury in a patient receiving a high dose regimen for haematological malignancies has not been reported previously. We present one such case of methotrexate related acute lung injury in a patient of primary CNS lymphoma receiving high dose methotrexate.

To describe the pathological findings, immunohistochemical localization of viral antigen and tissue reverse transcriptase polymerase chain reaction (RT-PCR) findings of different organs in cases of fatal H1N1 influenza virus infection from North India.Nine patients positive for H1N1 virus by a throat swab real-time RT-PCR (rRT-PCR) were included. Underlying risk factors included pregnancy, respiratory diseases, rheumatic heart disease, and chronic kidney disease. Pathological evidence of tracheitis, necrotizing bronchiolitis and diffuse alveolar damage was noted in all of the cases. Influenza viral antigen was observed by immunohistochemistry in the epithelium of the tracheobronchial tree, bronchial glands, gland ducts, and, less frequently, the alveolar epithelial cells. Viral particles were confirmed by electron microscopy in three autopsy cases. Tissue rRT-PCR for H1N1 viral RNA was positive in lung samples, but negative in other organs. Secondary bacterial pneumonia, cytomegalovirus infection and angio-invasive zygomycosis were detected.The pulmonary findings are similar to those described in past pandemics. Secondary fungal and viral infections, which have not been reported previously, were noted. Although the number of cases in this study is small, the findings reinforce the notion that changes in extrapulmonary organs are attributable to multiorgan dysfunction syndrome rather than a viral cytopathic effect, and that there is no transplacental transmission of virus.

To evaluate the presence of peripheral neuropathy (PN) in newly diagnosed treatment-naive patients with multiple myeloma (MM), 29 patients and 25 age and sex matched controls underwent electrophysiological studies. Patients with associated diabetes, alcoholism, peripheral vascular disease and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M component and skin changes) were excluded from the study. The median age of patients was 56 years (range 28-82) and the sex ratio was 2.6:1. Eighteen (62.1%) patients were found to have evidence of PN by history and clinical examination alone (two patients), both clinical and electrophysiological evidence (five patients) and only electrophysiological evidence (11 patients). Out of 25 healthy controls, only two patients had evidence of PN by electrophysiological studies (cases vs. controls, p < 0.002). The commonest nerve involvement was in the form of sensory-motor axonal neuropathy followed by sensory-motor demyelinating neuropathy. This information may impact therapeutic and prognostic decision-making in newly diagnosed patients with MM.

Rubella is traditionally considered a childhood disease but it has the potential to cause outbreaks in closed communities when a susceptible population accumulates. The present study reports an outbreak of rubella among healthcare workers in the pediatric center of a tertiary care North Indian hospital. The cases of rubella were identified by clinical features and confirmed by the detection of anti-rubella IgM antibodies in blood by enzyme linked immunosorbent assay. A total of 23 cases of rubella occurred over a period of one and a half month, out of which 9 (39%) were males. All the patients were in the age group of 21–35 years. None of the patients gave a history of rubella vaccination. This outbreak of rubella occurred due to the accumulation of a susceptible population in a closed hospital environment. There is need for the introduction of rubella vaccination in healthcare workers to prevent outbreaks at work place. J. Med. Virol. 82:341–344, 2010. © 2009 Wiley-Liss, Inc.