A study of outcome in COVID-19 patients receiving casirivimab-imdevimab

Objectives: In December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, as a respiratory tract infection causing symptoms, such as fever, chills, dry cough, fatigue, and shortness of breath. Despite the low mortality rate of COVID-19, patients with comorbidities such as hypertension, cardiovascular disease, and diabetes mellitus seem to be prone to more severe symptoms and to a higher mortality rate than others. Such patients are shown to benefit from usage of monoclonal antibodies. Casirivimab-imdevimab is a cocktail made up of two non-competing, neutralizing human immunoglobulin G1 antibodies that target the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and block viral entry into human cells. We assessed the clinical profile and outcome of 42 patients who received the antibody cocktail. Materials and Methods: Casirivimab-imdevimab was administered to COVID-positive patients with mild severity. Forty-two patients who satisfied the inclusion criteria received casirivimab-imdevimab and were included in the study. Demographic and clinical data were tabulated in Microsoft Excel and statistics were run in OpenEpi software. Results: No adverse reactions were seen in any of the patients. Among the 42 patients, there were no deaths. Twentytwo (52.3%) patients improved, while 20 (47.6%) worsened after receiving the antibody cocktail. Out of 21 (50%) patients who did not have any comorbidity, 13 (30.9%) worsened after receiving the drug and 8 (19%) improved, while among those with comorbidities, 7 (16.6%) worsened and 14 (33.3%) improved (P < 0.05). Thirteen (30.9%) unvaccinated patients improved, while 14 (33.3%) worsened, whereas 6 (14.2%) fully vaccinated patients improved while only 2 (4.7%) worsened. Among the patients who were administered the cocktail within 5 days of onset of symptoms, 12 (28.5%) improved and 10 (23.8%) worsened, whereas among those who received the drug between 6 and 10 days of symptom onset, ten improved, and ten worsened. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients. Conclusion: None of the 42 patients developed any reaction to casirivimab-imdevimab. There were no deaths in the study population. About 52.3% of the patients improved and 47.6% worsened after receiving the cocktail. About 33.3% of the comorbid patients improved. There was no statistically significant association between vaccination status and outcome, and infusion interval and outcome in these patients.

Fine Needle Aspiration Cytology, a Useful Tool for the Diagnosis of Specific Leprous Osteitis

Leprosy is known to affect the nerves, skin, respiratory tract and eyes commonly. Leprosy also afflicts bones, the sites of predilection for bone damage include small bones of hands and feet. Advanced bone changes are rarely encountered. We describe a case of specific leprous osteitis diagnosed by fine needle aspiration cytology (FNAC). An 18 year old male presented with multiple swellings and ulcers over the limbs since two months. A 3x2 cm hard swelling with ulceration was seen over distal left ring finger, X-ray of which showed an osteolytic lesion over the distal interphalangeal joint (DIP). FNAC from the lytic lesion showed foamy macrophages, a few lymphocytes and epithelioid cells with strongly positive staining for acid-fast bacilli (AFB). A diagnosis of specific leprous osteitis was made. FNAC is a simple, cost effective and minimally traumatic procedure and may be used as a mode of investigation for the diagnosis of specific leprous osteitis.

Characterization, In Vitro Antioxidant And Hepatoprotective Activity Of Fungal Endophytic Extracts Of Andrographis Paniculata Leaves In Ccl4 Induced Hepatotoxicity

Objective: To isolate and characterize the endophytic fungi from the leaves of Andrographis paniculata for free radical scavenging antioxidant and hepatoprotective activity against CCl4 induced hepatotoxicity Methods: Two fungal endophytes, APLF-3 (Andrographis paniculata leaf fungi-3) and APLF-4 (Andrographis paniculata leaf fungi-4) were isolated from leaves of Andrographis paniculata to get chloroform (A3C, A4C), ethyl acetate (A3EA, A4EA) and n butanol (A3nB, A4nB) extracts. rDNA sequencing by PCR technique was carried out for identification of APLF-3 and APLF-4. All the APLF-3 and APLF-4 extracts were assayed for in vitro free radical scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical and reducing power. Then, A4EA and A4nB were screened for hepatoprotective activity against CCl4 induced hepatotoxicity at 50 mg/kg and100 mg/kg doses. Results: The endophytic fungi, APLF-3 and APLF-4, were identified as Phyllosticta sp. ZLY-2010 isolate M13 and Aspergillus tubingensis strain Cs/7/2 respectively based on their morphological and molecular characterization. A4EA and A4nB showed significant in vitro free radical scavenging activity as compared to other extracts. A4EA and A4nB (50 mg/kg and100 mg/kg) reversed the increased serum biochemical parameters as compared to CCl4 treated group (p<0.001). A4EA and A4nB (100 mg/kg p. o) also restored the LPO, SOD and CAT levels. Conclusion: These findings suggested that the extracts (A4EA and A4nB) obtained from endophytic fungi APLF-4 contributed towards hepatoprotective activity.

Conflict of interest disclosure and interpretation – rest assured the medical professional in the audience is perceptive, alert and smart

INTRODUCTION:We present data from a systematic survey on conflict of interest (COI) disclosure and its interpretation by the doctors participating in continuing medical education (CME).METHODS:A brief 12 question online Google survey with multiple choice options (read, select, and click) was done among Indian practicing doctors using links shared through WhatsApp through the internet over a 72 h period.RESULTS:Of the 386 replies, 373 unique replies were eligible for evaluation. The majority found CME activities beneficial. About 73% of participants would watch out for bias, even if the speaker shows COI disclosure slide. The use of brand/trade names was considered as a flag for bias by the majority. About 99% wanted the speaker to show a final take home message slide. Cross verification of the data presented by comparing to published data was done in more than 75% of instances by only 25% of the participating doctors. A significantly higher number of doctors found bias when CME activities were being organized by the health-care industry as compared to programs of medical bodies/societies/organizations.DISCUSSION:COI considerations are given due to the importance of medical professionals. However, doctors are smart enough to understand the limitations of such disclosures and remain alert to ensure they are not influenced by any bias. Take home message slide gives the presenters opportunity to share their insights and allows the audience to make their own judgment on the impartiality of the data presented. The doctors are aware that bias could be more when CME activities are organized by healthcare industry and take appropriate precautions.CONCLUSION:COI is is given due importance by the medical professionals. COI disclosures are often incomplete. Doctors remain alert to ensure they are not influenced by biased presentations. Concluding take home message slide is unanimously recommended. Presentation bias is more when healthcare industry is directly organizing educational and promotional activities.

Polymorphisms in cytotoxic T-lymphocyte associated antigen 4 gene does not affect scytotoxic T-lymphocyte associated antigen 4 levels in human papillomavirus-infected women with or without cervical cancer

Background: Cervical cancer (CaCx) is the second most common cancer in Indian women. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) + 49 AA polymorphism is known to be associated with CaCx. Current attempt is to use immunotherapy for the treatment of metastatic melanoma and metastatic castration-resistant prostate cancer, i.e., blocking of CTLA-4 using a fully human monoclonal CTLA-4 antibody to disrupt its inhibitory signal. This allows the CTLs to destroy the cancer cells. There is no information available on the soluble level of CTLA-4 on which the immunotherapy is targeted. This is specifically in Indian population including cases with CaCx. Objective: The aim of this study is to evaluate the levels of soluble CTLA-4 (sCTLA-4) in human papillomavirus (HPV)-infected women with or without CaCx and their association with the polymorphism at CTLA-4 + 49 A/G and CTLA-4 ?318 C/T genotypes. Materials and Methods: This is an exploratory case–control study involving two groups of HPV-infected women, the cases were with invasive CaCx and the control group was women with the healthy cervix. sCTLA-4 levels were measured using ELISA in 92 CaCx cases and 57 HPV-positive women with the healthy cervix. Results: Both cases and controls have similar sCTLA-4 levels. Comparison of CTLA-4 + 49A/G and ?318 C/T genotypes with sCTLA-4 levels among cases and control also did not show any statistically significant difference. Conclusion: The present study suggests sCTLA-4 levels are not affected by a polymorphism at + 49 A>G CTLA-4. Hence, levels of CTLA-4 are similar in both CaCx cases and control group.

Awareness Of Body Donation And Embalming Among Medicos: Questionnaire Based Study

Background: The knowledge of the ossified ligaments in the base of the skull is of utmost important for anatomical,clinical and anthropological correlations. One such ligament extending from the lateral pterygoid plate to theunder surface of greater wing of sphenoid is named as Pterygoalar ligament and is named as Pterygoalar barafter its partial or complete ossification. This Pterygoalar bar is of great significance as it obscure the view offoramen ovale to approach it for anaesthetic , therapeutic purpose either suprazygomatic or infrazygomatic via.Also its enclosed foramen crotaphitico buccinatorius which is comparatively smaller than any other foramenmay compress the structures passing through it, probably the structures emerging out of foramen ovale may takeup a route via this foramen and get entrapped, which may lead to either neurovascular compression disorder.Objective: The aim of this study was to determine the prevalence of thickened bony bar, pterygoalar bony bridgesand to analyze morphometrically the homonyms foramen in a collection of contemporary skulls and discusstheir clinical implications.Materials and Methods: The present study was performed with 90 dried adult human skulls. Base of the skull wasexamined with naked eye, on both the sides for the presence of abnormal osseous structures from the lateralpterygoid plate.Results and Discussion: In the current study, we presented only one skull with unilateral complete pterygoalar barand 11 skulls with unilateral incomplete pterygoalar bar. The pterygoalar bar and pterygoalar foramen are rareclinical features but their presence may be of clinical importance in the event of trigeminal nerve injection oranaesthesia

Synthesis, Characterization and Antimicrobial Activities of Some Novel Heterocyclic Schiff Bases.

A series of heterocyclic schiff bases have been synthesised by the condensation of 2-amino-4,6- dimethyl benzothiazole and selected heterocyclic α- hydroxy aldehyde and α-hydroxy ketones. The structures of the products were confirmed by spectral analysis (IR, 1H NMR, 13C NMR and Mass). All the newly synthesized compounds were screened for their antibacterial and antifungal activity against different fungal and bacterial strains.

Antiviral drug profile of human influenza A & B viruses circulating in India: 2004-2011.

background & objectives: Recent influenza antiviral resistance studies in South East Asia, Europe and the United States reveal adamantane and neuraminidase inhibitor (NAIs) resistance. This study was undertaken to evaluate antiviral resistance in influenza viruses isolated from various parts of India, during 2004 to 2011. methods: Influenza viruses were analyzed genetically for known resistance markers by M2 and NA gene sequencing. Influenza A/H1N1 (n=206), A/H3N2 (n=371) viruses for amantadine resistance and A/H1N1 (n=206), A/H3N2 (n=272) and type B (n=326) for oseltamivir resistance were sequenced. Pandemic (H1N1) (n= 493) isolates were tested for H274Y mutation by real time reverse transcription (rRT)-PCR. Randomly selected resistant and sensitive influenza A/H1N1 and A/H3N2 viruses were confirmed by phenotypic assay. results: Serine to asparagine (S3IN) mutation was detected in six isolates of 2007-2008.One dual-resistant A/H1N1 was detected for the first time in India with leucine to phenylalanine (L26F) mutation in Mm2 gene and H274Y mutation in NA gene. A/H3N2 viruses showed an increase in resistance to amantadine from 22.5 per cent in 2005 to 100 per cent in 2008 onwards with S3IN mutation. Fifty of the 61 (82%) A/H1N1 viruses tested in 2008-2009 were oseltamivir resistant with H274Y mutation, while all A/H3N2, pandemic A/H1N1 and type B isolates remained sensitive. Genetic results were also confirmed by phenotypic analysis of randomly selected 50 resistant A/H1N1 and 40 sensitive A/H3N2 isolates. Interpretation & conclusions: Emergence of influenza viruses resistant to amantadine and oseltamivir in spite of negligible usage of antivirals emphasizes the need for continuous monitoring of antiviral resistance.

Ectodermal dysplasia: familial report of six cases.

Ectodermal dysplasia is a hereditary disease characterized by a congenital dysplasia of one or more ectodermal structures and their accessory appendages. There are two main types, Hypohidrotic/Christ-Seimens- Tourian Syndrome and Hidrotic/Clouston syndrome. Common manifestations include defective hair follicles and eyebrows, frontal bossing with prominent supraorbital ridges, nasal bridge depression and protuberant lips. Intraorally common findings are anodontia or hypodontia and conical shaped teeth. The patient may suffer from dry skin, hyperthermia and unexplained high fever because of the deficiency of sweat glands. The present article reports unique case series of ectodermal dysplasia cases in two families, where three generations in the both the families were affected.

Applications of Micellar Liquid Chromatography in Bioanalysis: A Review.

Micellar liquid chromatography (MLC) is one of the very important analytical techniques. It contains mobile phase added with surfactants above its critical micellar concentration and the stationary phase is modified with surfactant monomers. So, micelles alter the solubilising capability of the mobile phase which forms diverse interactions with major implications in retention and selectivity. It is an alternative to conventional reversed phase liquid chromatography. It allows direct injection of physiological fluids, analysis of pharmaceutical compounds, physiological partitioning process. MLC (micelle liquid chromatography) has proved time saving as compared to other analytical technique like HPLC and ion-pairing. Applicability of MLC is increased in the field of bioanalysis. It is used to analyze different samples of drugs in serum, urine, food etc. In this review we have focused on the various examples of use of MLC in bioanalysis. This review also contains basic information about MLC such as micellar mobile phase, stationary phase, surfactants, and fundamental studies such as retention behavior and partition coefficient.

Frequency and causes for exclusion from randomization of healthy volunteers screened for a phase 1 study in India.

Background. Only a proportion of screened potential participants were actually randomized while conducting a phase 1 study of a humanized rabies monoclonal antibody. We aimed to assess the challenges in defining who is a normal volunteer and the issues that affect volunteer recruitment and thus accrual. Methods. One hundred and fifty-six volunteers were screened and 74 (47.4%) were randomized in a phase 1 study. Data on all participants screened for the study were analysed and reasons for their non-randomization were classified. Results. The reasons for volunteers not being randomized were: (i) deranged laboratory parameters (n=62); (ii) nonlaboratory causes (n=4); and (iii) withdrawal of consent (n=16). A large proportion of screen failures were due to low haemoglobin levels, which led to the protocol being amended midway during the study. An informal interview of those who declined consent showed that they had only wanted to get themselves investigated thoroughly or were interested in getting their HIV status evaluated. Conclusions. Our study shows that <50% participants screened for a phase 1 study in a developing country actually get randomized. The main reason for non-randomization is abnormal laboratory tests. This may help investigators and sponsors to plan protocols better, define normal ranges with acceptable variations based on their own populations a priori and have more pragmatic accrual targets.

Adaptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm.f) Boj. in acute and chronic stress paradigms in rodents.

Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity.

Chromium exposure study in chemical based industry.

176 chromium-exposed and 30 control subjects were selected for this study. Blood samples (3 ml) were collected for the estimation of chromium. The data on chromium concentration indicated a significant higher level of chromium in the blood of the exposed workers as compared to the control. There was no significant correlation between the mean blood and environmental chromium level. This study suggests that exposure to chromium may have some effect on the health of workers, even though the dose response relationship could not be established between blood chromium and environmental chromium levels. This study suggests that exposure to chromium may have some effect on the health of workers, even though the dose response relationship could not be established between blood chromium and environmental chromium levels. Study also indicates that the environmental levels to Cr are well below the permissible levels at all the sites of the industry at the time of survey even though the blood Cr levels were observed high in 14.8% of workers and some of them were having Cr related morbidity. Therefore, preventive and engineering control measures are suggested to minimize the chromium exposure in the chromium based industry located in Gorwa industrial estate at Baroda, Gujarat. About three months period was taken to complete this study.

Benign fibrous histiocytoma of bone: a case report.

Benign fibrous histiocytoma (BFH) occurs commonly in soft tissues with very few cases of BFH of bone on record. We report a case of BFH of tibia in fifty year old male who presented with supracondylar fracture femur due to trivial fall and a brief review of literature.

Papillon Lefevre syndrome.

Papillon Lefèvre syndrome is a rare disease characterized by skin lesions caused by palmar-plantar hyperkeratosis, and severe periodontal destruction involving both the primary and permanent dentitions. It is transmitted as an autosomal recessive condition and consanguinity of parents is evident in about one-third of cases. Pyogenic liver abscess is an increasingly recognized complication. We report a new case of this association and review the current literature.

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases.

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.

Occupational injuries: is job security a factor?

CONTEXT: Although a large number of contributing factors of occupational injury causation are explored meticulously to explain the phenomenon of higher occupational injury occurrence in some subjects, it has remained a matter of controversy. AIMS: In this study, an effort is made to explore whether job security has any contribution in explaining higher susceptibility of some workers. SETTINGS AND DESIGN: This was a retrospective occupational injury record study conducted in an industry of eastern India. MATERIALS AND METHODS: Along with the study of injury records of 5 years, an interview was also conducted involving 726 workers (including permanent and temporary workers both) of the factory. STATISTICAL ANALYSIS USED: Comparison was made between permanent and temporary workers by using the Mann-Whitney U-test and the chi-square test. A theoretical model of Poisson's distribution was used to compare between expected and real occurrence. RESULTS: Although two worker groups were very similar in relation to age, level of education, habits, and nature of work, accident frequency and severity rates were found to be significantly higher in temporary workers. CONCLUSIONS: This study concluded that the higher accident risk of the temporary workers might have been due to the less effective experience as well as due to lack of job security inherent in such workers.

Influenza surveillance in Pune, India, 2003.

Influenza surveillance was conducted in Pune, India in 2003. A total of 573 throat swabs/ nasal swabs (TS/NS) and 190 nasopharyngeal aspirates (NPA) were collected from 763 in- and out-patients who were mostly children aged 0-16 years. TS/NS (507/573) and NPA (42/190) specimens were processed in MDCK cell cultures and identified with the hemagglutination inhibition test (HI). A total of 37 influenza viruses was isolated: twenty-three type A (H3N2) and 14 type B of the Yamagata lineage were isolated from 29 children and 8 adults. Three type A (H3N2) isolates were characterized as being similar to A/Panama/2007/99 like, A/Korea/770/2000 like, and B/Sichuan/379/99 like strains.

Use of liposomal amphotericin B in bone marrow transplant.

Increasing number of transplants worldwide has resulted in an increase in the incidence of fungal infections. Prolonged neutropenia, immunosuppression and graft vs. host disease all result in high predisposition to fungal infections. The likelihood of developing a fungal infection increases with the severity and duration of neutropenia, which, in the case of cancer or chemotherapy for the treatment of hematological malignancies, can range from a few days to several weeks. Invasive fungal infections are difficult to diagnose and neutropenic patients with fever often receive empirical antifungal therapy. This provides a rationale for the prophylactic use of antifungal agents. The empirical use of liposomal amphotericin B has overcome some of the difficulties usually found in this setting. The majority of clinical efficacy data related to liposomal amphotericin B are derived from compassionate use studies and case series. The major advantage of these liposomal formulations of amphotericin B is a reduction in amphotercin toxicity. Use of liposomal amphotericin has been shown to be a cost-effective approach abroad and the same has been our experience also. Commercially ambisome and Fungisome are the only products that contain true liposomes. Unlike ambisome, which needs to be used in dose of 3 mg/kg/day Fungisome is effective in the dose of 1-3 mg/kg bodyweight. The Indian liposomal preparation has shown to be safe and effective used in over 150 transplant patients in our experience. We conclude that the liposomal amphotericin is better-tolerated and also gives,better responses in documented fungal infections.