Bacteriology of endotracheal tube biofilms and antibiotic resistance: a systematic review.

Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can appear to be many times more resistant to antibiotics or disinfectants. This systematic review explores the prevalence and microbial profile associated with biofilm production of bacteria isolated from endotracheal tubes and its associations with antimicrobial resistance. A comprehensive search was performed on databases PubMed, Embase, and Google Scholar for relevant articles published between 1st January 2000 and 31st December 2022. The relevant articles were exported to Mendeley Desktop 1.19.8 and screened by title and abstract, followed by full text screening based on the eligibility criteria of the study. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) customized for cross-sectional studies. Furthermore, the prevalence of antimicrobial resistance in biofilm-producers isolated from endotracheal tube specimens was investigated. Twenty studies encompassing 981 endotracheal tubes met the eligibility criteria. Pseudomonas spp. and Acinetobacter spp. were predominant isolates among the biofilm producers. These biofilms provided strong resistance against commonly used antibiotics. The highest resistance rate observed in Pseudomonas spp. was against fluoroquinolones whereas the least resistance was seen against piperacillin-tazobactam. A similar trend of susceptibility was observed in Acinetobacter spp. with a very high resistance rate against fluoroquinolones, third-generation cephalosporins and carbapenems. In conclusion, endotracheal tubes were associated with colonization by biofilm forming bacteria with varying levels of antimicrobial resistance. Biofilms may promote the occurrence of recalcitrant infections in endotracheal tubes which need to be managed with appropriate protocols and antimicrobial stewardship. Research focus should shift towards meticulous exploration of biofilm-associated infections to improve detection and management.

Assessing structural insights into in-house arylsulfonyl L-(+) glutamine MMP-2 inhibitors as promising anticancer agents through structure-based computational modelling approaches.

MMP-2 is potentially contributing to several cancer progressions including leukaemias. Therefore, considering MMP-2 as a promising target, novel anticancer compounds may be designed. Here, 32 in-house arylsulfonyl L-(+) glutamines were subjected to various structure-based computational modelling approaches to recognize crucial structural attributes along with the spatial orientation for higher MMP-2 inhibition. Again, the docking-based 2D-QSAR study revealed that the Coulomb energy conferred by Tyr142 and total interaction energy conferred by Ala84 was crucial for MMP-2 inhibition. Importantly, the docking-dependent CoMFA and CoMSIA study revealed the importance of favourable steric, electrostatic, and hydrophobic substituents at the terminal phenyl ring. The MD simulation study revealed a lower fluctuation in the RMSD, RMSF, and Rg values indicating stable binding interactions of MMP-2 and these molecules. Moreover, the residual hydrogen bond and their interaction analysis disclosed crucial amino acid residues responsible for forming potential hydrogen bonding for higher MMP-2 inhibition. The results can effectively aid in the design and discovery of promising small-molecule drug-like MMP-2 inhibitors with greater anticancer potential in the future.

Exploration of structural alerts and fingerprints for novel anticancer therapeutics: a robust classification-QSAR dependent structural analysis of drug-like MMP-9 inhibitors.

Among various matrix metalloproteinases (MMPs), overexpression of MMP9 has been established as a key player in a variety of cancers. Therefore, MMP9 has emerged as a promising biomolecule that may be targeted to design potent inhibitors as novel anticancer therapeutics. In this study, a large database containing 1,123 drug-like MMP-9 inhibitors was considered for robust classification-dependent fragment-based QSAR study through SARpy, Bayesian classification, and recursive partitioning analyses and were validated by both internal and external validation techniques. In a nutshell, all these classification-dependent techniques revealed some common structural alerts and sub-structural fingerprints responsible for modulating MMP-9 inhibition. These observations are in agreement with the interactions obtained from the ligand-bound co-crystal structures of MMP-9 justifying the robustness of the current study. Finally, based on these crucial structural fragments, some new lead compounds were designed and further validated by the binding mode of interaction analysis. Therefore, these findings may be beneficial in designing novel and potential MMP-9 inhibitors in the future as a weapon to combat several cancers.

Chronic Liver Disease Secondary to Chronic Budd Chiari Causing Osteomalacia Leading to Pathological Fractures.

INTRODUCTION: Metabolic disturbances of bone are common in patients of CLD manifesting as osteoporosis and osteopenia while osteomalacia is rare. MATERIALS: 34 years old lady with history of portal vein thrombosis and CLD since 2008 presented with complaints of anorexia, early satiety, nausea, vomiting weight loss for 8 months and syncopal attack followed by fall on ground leading to multiple fractures in both lower limbs and left upper limb. Investigations including hemogram, metabolic profile, X-rays, anemia workup, Vitamin D3, parathyroid hormone (PTH), hormone profile, CA-125, 24-hour urinary calcium, USG were planned. RESULT: On presentation her BP=106/64 mm Hg, PR = 98, RBS = 104. GPE showed cachexia, severe pallor, bipedal edema, deformed elbow joint, thoracic kyphosis with cervical lordosis. Hemogram and metabolic panel were suggestive of severe anemia, thrombocytopenia, deranged LFT, increased ALP, anemia of chronic disease (AOCD), X-rays suggestive of multiple fractures. Possiblity of metabolic bone disease (hepatic osteodystrophy) was kept. Further investigations showed Vitamin D deficiency, raised PTH, low 24-hour urinary calcium and FSH was raised for age. Diagnosis of osteomalacia was made and patient was started vitamin D and calcium supplementation, normocalcemia achieved and PTH and ALP settled in months. CONCLUSION: Patients with liver disease should be investigated for the presence of hepatic osteodystrophy, to allow the identification and the correction of risk factors and start of the therapeutic program. Niranjan Gangoor, Sanjay Neeralagi, Gayathri Karnataka Institute of Medical Sciences, Hubballi, Karnataka, India Introduction: Liver plays an important role in the metabolism of thyroid hormones, as it is the most important organ in the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) by Type 1 deiodinase. MATERIALS: This Prospective observational study included 100 liver cirrhosis patients Serum FT3, FT4, and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassay. Results were also analyzed for severity of liver disease according to Child-Turcotte-Pugh (CTP) (Class A, B, and C), model for end-stage liver disease (MELD) score, and HE grades. RESULT: Most common etiology was alcohol (58%) and presentation was gross ascites (77%). Cirrhosis patients had statistically significant lower level of FT3 and FT4 but had higher level of TSH. Cirrhosis with HE (n = 38) had significantly lower lever of FT3 compared with cirrhosis without HE (n = 62). In all cirrhotic patients, FT3 and FT4 were negatively correlated, but TSH level was positively correlated with total leukocyte counts, serum total bilirubin, aspartate transaminase, alanine transaminase, globulin, prothrombin time blood urea, serum creatinine, CTP, and MELD score. CONCLUSION: The mean FT3 and FT4 levels were significantly decrease and mean TSH levels were significantly increase in liver cirrhosis patients. Level of FT3, FT4, and TSH also correlate with the severity of liver disease, level of FT3 can be used as prognostic marker for liver cirrhosis patients. References Patira NK, Salgiya N, Agrawal D. Correlation of thyroid function test with severity of liver dysfunction in cirrhosis of liver. J Assoc Physicians India 2019;67(3):51-54. Kumar A, Ahuja V, Kaur I, et al. Prevalence of thyroid dysfunction in patients of cirrhosis of liver and its correlation with severity of cirrhosis. Int J Adv Res 2020;8:91-95.

A comparative quantitative structural assessment of benzothiazine-derived HDAC8 inhibitors by predictive ligand-based drug designing approaches.

Histone deacetylase 8 (HDAC8) is a verified biomolecular target associated with diverse diseases including cancer. Though several HDAC inhibitors emerged effective against such diseases, no selective HDAC8 inhibitor is approved to date. Therefore, the development of potent HDAC8-selective inhibitors is inevitable to combat such diseases. Here, some benzothiazine-derived HDAC8 inhibitors were considered for a comparative QSAR analysis which may elucidate the prime structural components responsible for modulating their efficacy. Several outcomes from these diverse modelling techniques justified one another and thus validated each other. The ligand-based pharmacophore modelling study identified ring aromatic, positive ionizable, and hydrophobic features as essential structural attributes for HDAC8 inhibition. Besides, MLR, HQSAR and field-based 3D-QSAR studies signified the utility of the positive ionizable and hydrophobic features for potent HDAC8 inhibition. Again, the field-based 3D-QSAR study provided useful insight regarding the substitution in the fused phenyl ring. Moreover, the current observations also validated the previously reported molecular docking observations. Based on the outcomes, some new molecules were designed and predicted. Therefore, this comparative structural analysis of these HDAC8 inhibitors will surely assist in the development of potent HDAC8 inhibitors as promising anticancer therapeutics in the future.

A quantitative structural analysis of AR-42 derivatives as HDAC1 inhibitors for the identification of promising structural contributors.

Alteration and abnormal epigenetic mechanisms can lead to the aberration of normal biological functions and the occurrence of several diseases. The histone deacetylase (HDAC) family of enzymes is one of the prime regulators of epigenetic functions modifying the histone proteins, and thus, regulating epigenetics directly. HDAC1 is one of those HDACs which have important contributions to cellular epigenetics. The abnormality of HDAC is correlated to the occurrence, progression, and poor prognosis in several disease conditions namely neurodegenerative disorders, cancer cell proliferation, metastasis, chemotherapy resistance, and survival in various cancers. Therefore, the progress of potent and effective HDAC1 inhibitors is one of the prime approaches to combat such diseases. In this study, both regression and classification-based molecular modelling studies were conducted on some AR-42 derivatives as HDAC1 inhibitors to elucidate the crucial structural aspects that are responsible for regulating their biological responses. This study revealed that the molecular polarizability, van der Waals volume, the presence of aromatic rings as well as the higher number of hydrogen bond acceptors might affect prominently their inhibitory activity and might be responsible for proper fitting and interactions at the HDAC1 active site to pertain effective inhibition.

Applying comparative molecular modelling techniques on diverse hydroxamate-based HDAC2 inhibitors: an attempt to identify promising structural features for potent HDAC2 inhibition.

Histone deacetylase 2 (HDAC2) has been implicated in a variety of cardiovascular and neurodegenerative disorders as well as in cancers. Thus, HDAC2 has become an exclusive target for anticancer drug development. Therefore, the development of newer HDAC2 inhibitors in disease conditions is a prime goal to restrain such a scenario. Although a handful of HDAC inhibitors was accepted for the treatment of HDAC-related disease conditions, the non-selective nature of these entities is one of the major setbacks in the treatment of specific HDAC isoform-related pathophysiology. In this framework, the analyses of pre-existing molecules are essential to identify the important structural features that can fulfil the requirements for the cap and linker moieties to obtain potent and effective HDAC2 inhibition. Thus, in this study, the implementation of a combined comparative 2D and 3D molecular modelling techniques was done on a group of 92 diverse hydroxamate derivatives having a wide range of HDAC2 inhibitory potency. Besides other crucial features, this study upheld the importance of groups like triazole and benzyl moieties along with the molecular fields that are crucial for regulating HDAC2 inhibition. The outcomes of this study may be employed for the designing of HDAC2 inhibitors in future.

Changes in Clinical Practice amongst Nepalese Otolaryngologists during COVID-19 Pandemic.

Background COVID-19 pandemic changed clinical practices more so for otolaryngologists due to inevitable risk of exposure. Objective To assess the changes in the clinical practice among Nepalese otolaryngologists during this pandemic. Method It was an observational study conducted as an online survey in the first two weeks of December 2020. A questionnaire pertaining to changes in clinical practice was mailed to 190 registered otolaryngologists working in various provinces of Nepal. Data were entered in Microsoft Excel 2007 and analysed in percentages. Result Out of the 77 (40.5%) who responded, nearly 50% resumed clinical practice after a month of national lockdown restarting everyday consultation by 64.9% mostly in hospital setting (81.8%) after screening patients via fever clinic by 87%. Modifications in clinical examinations was mostly done for neck (85.7%), oral cavity (44.2%) and nose (29.8%) examination with least with for ear examination (3.9%) Regular endoscopic evaluation was avoided by 19.4%. Only around 57% used adequate personal protective equipment. There was 93.5% reduction in elective operations. Mandatory COVID test was done by 89.6% mostly with reverse transcriptase polymerase chain reaction (95.9%) prior to semi-urgent case. Conclusion Changes in clinical practice were adapted to mitigate viral transmission. The changes were evident in the outpatient department where most patients were screened for fever and modifications made in the clinical examinations. Personal protective equipments were worn when available. Operative lists were limited to semi-urgent and urgent cases with covid testing customarily done for semi-urgent cases.

A robust classification-dependent multi-molecular modelling study on some biphenyl sulphonamide based MMP-8 inhibitors.

Matrix metalloproteinases (MMPs) are a group of zinc and calcium-dependent endopeptidases, which contribute to different physiological and biological activities via extracellular matrix (ECM) degradation. Matrix metalloproteinase-8 (MMP-8) belongs to type-II collagenases of the MMP family that has contribution in several physiological disorders such as cardiovascular diseases, joint, renal, digestive and respiratory disorders as well as in cancer. In clinical study, MMP-8 is found to be associated with periodontal disease condition. Therefore, MMP-8 specific inhibitors should be developed to target these disorders. The biphenyl sulphonamide (BPS) moiety is one of the crucial structural characteristics found in several MMP-8 inhibitors. Here, different classification-based molecular modelling methods were used to explore the structural features that lead to the activity variation of a series of MMP-8 inhibitors possessing a BPS moiety. Our current classification-based structural analysis of these BPS-derived MMP-8 inhibitors was able to identify the importance of several structural features such as the tetrahydroisoquinoline and N-Boc pyridyl groups, which have positive influences on MMP-8 inhibition. This study was also reflected the importance of the zinc-binding groups (ZBGs) like the hydroxamate and phosphonate for potent and sub-nanomolar range MMP-8 inhibition, which may benefit the development of highly potent MMP-8 inhibitors.

Robust classification-based molecular modelling of diverse chemical entities as potential SARS-CoV-2 3CLpro inhibitors: theoretical justification in light of experimental evidences.

COVID-19 is the most unanticipated incidence of 2020 affecting the human population worldwide. Currently, it is utmost important to produce novel small molecule anti-SARS-CoV-2 drugs urgently that can save human lives globally. Based on the earlier SARS-CoV and MERS-CoV infection along with the general characters of coronaviral replication, a number of drug molecules have been proposed. However, one of the major limitations is the lack of experimental observations with different drug molecules. In this article, 70 diverse chemicals having experimental SARS-CoV-2 3CLproinhibitory activity were accounted for robust classification-based QSAR analysis statistically validated with 4 different methodologies to recognize the crucial structural features responsible for imparting the activity. Results obtained from all these methodologies supported and validated each other. Important observations obtained from these analyses were also justified with the ligand-bound crystal structure of SARS-CoV-2 3CLpro enzyme. Our results suggest that molecules should contain a 2-oxopyrrolidine scaffold as well as a methylene (hydroxy) sulphonic acid warhead in proper orientation to achieve higher inhibitory potency against SARS-CoV-2 3CLpro. Outcomes of our study may be able to design and discover highly effective SARS-CoV-2 3CLpro inhibitors as potential anticoronaviral therapy to crusade against COVID-19.

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study.

The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future.

Recovery Pattern in Different Surgical Approaches on Thoracic Enhanced Recovery based Fourteen-Step Protocol in Patients Undergoing Cardio-thoracic Surgery at University Hospital of Nepal.

Background Cardio-thoracic surgery involves open and minimally invasive techniques. Enhanced recovery after surgery is used for early recovery from surgery. Enhanced recovery after surgery decreases hospital stay duration. Patients undergoing Enhanced recovery after surgery after video assisted thoracic surgery use less pain killers and have less hospital cost. There has not been any study on outcomes on patient who follow physiotherapy protocol designed in our setting. Objective To find the physiotherapy outcomes in patients undergoing thoracic enhanced recovery after surgery (T-ERAS) based 14 step protocol locally designed at Dhulikhel Hospital, Kathmandu University Hospital (DH, KUH). Method This is a retrospective cross sectional observational study. All the cases who underwent cardiothoracic surgery were classified based on the approach of chest surgery performed into groups Sternotomy, Thoracotomy and Video Assisted Thoracic Surgery (VATS) groups. Patients were advised for Thoracic Enhanced recovery after surgery based on the protocol that has been devised at Dhulikhel Hospital. The recovery of patients based on activities they could perform was noted and analyzed. Result Both ICU stay and hospital stay in number of days were highest in thoracotomy (6.04 days) group while that was lowest in video assisted thoracic surgery group (1.67 days). There is a similar recovery until step 5, i.e. 2 days and rapid progression in further steps in video assisted thoracic surgery group while it is much slower in both sternotomy and thoracotomy groups. Conclusion Postoperative mobilization and physiotherapy enhance early healing and decrease hospital stay. Mean hospital stay and ICU stay were shorter for video assisted thoracic surgery cases compared to Thoracotomy and Sternotomy groups and the mean days to achieve different steps varied within the protocol between groups compared.

Impairment and Functional Status of People with Disabilities Following Nepal Earthquake 2015.

Background An earthquake of 7.8 magnitude with an epicenter at Gorkha on 25th April 2015 and a second earthquake of 6.5 magnitude with an epicenter at Sindhupalchwok on 12th May 2015 struck Nepal, killing more than 8,500 people and injuring over 18,500 individuals, and leading to various forms of disabilities. Objective To investigate the impairments and functional status of the earthquake victims through a survey. Method A survey was carried out in the catchment area of Bahunepati and Manekharka outreach centers of Sindhupalchowk district and Gaurishankar outreach center of Dolakha district of Dhulikhel Hospital. These were some of the most earthquake affected areas. Physical disability was identified using a disability survey form given by the Ministry of Women, Children and Social Welfare, Government of Nepal. World health organization disability assessment schedule (WHODAS 2.0) was used to identify the level of disability. Result Twenty-nine persons with disability (PWD) at Bahunepati, four PWD at Manekharkha and two PWD at Gaurishankar and their catchment areas were identified. Level of disability was an average of 56%, with the majority of survivors having upper extremities fractures (27.6%), followed by lower extremities fractures (17.2%) and miscellaneous injury (17.2%). A few spinal cord injuries and head injuries were also identified. Conclusion The level of disability among the injured people was high. Therefore, an urgent need of physiotherapy rehabilitation is warranted to improve the quality of life of the earthquake victims.

Influence of gastrointestinal events on treatment of osteoporosis in Asia-Pacific women: Perspectives from physicians in the MUSIC OS-AP study.

BACKGROUND: The objectives of the physician survey component of the MUSIC OS-AP study were to describe physicians' approaches to treatment of women with postmenopausal osteoporosis and to understand the influence of gastrointestinal (GI) events on treatment in clinical practice. METHODS: Physicians were recruited from 5 Asia-Pacific countries. Questionnaires collected information about physicians' standard practices for treatment of patients with osteoporosis, as well as their perspectives on the influence of GI events on osteoporosis treatment approaches. RESULTS: A total of 59 physicians participated in the study. The most frequently prescribed or recommended treatments were vitamin D (84% of patients), calcium (82%), and oral bisphosphonates (59%). When choosing a medication for treatment-naïve patients, GI sensitivity was often or always a factor for 79% of physicians. Among physicians not prescribing pharmacologic treatment, a mean of 18% of non-prescriptions were due to GI sensitivity. For patients with pre-existing GI conditions, physicians most frequently ranked use of non-oral osteoporosis medication as the first treatment strategy (47%), followed by co-prescription with a proton pump inhibitor or other gastro-protective agent (31%). For patients developing GI symptoms after starting pharmacologic treatment, the most frequently first-ranked management strategy was to check if patients were taking their osteoporosis medication correctly as prescribed (64%), followed by temporary discontinuation of the medication (i.e., a drug holiday) until GI events have resolved (31%) and co-prescription with a proton pump inhibitor or other gastroprotective agent (24%). CONCLUSIONS: These results suggest that GI events influence the prescribing practices of physicians in the Asia-Pacific region and sometimes result in non-treatment of women with osteoporosis.

Impact of gastrointestinal events on patient-reported outcomes in Asia-Pacific women with osteoporosis: baseline results of the MUSIC OS-AP study.

The purpose of this study was to describe the impact of gastrointestinal events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. The results of this study show that gastrointestinal events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis. PURPOSE: This study aimed to describe the impact of gastrointestinal (GI) events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. METHODS: The MUSIC OS-AP study included an observational cohort study of postmenopausal women with osteoporosis. Women were classified as untreated or treated, with treated patients further classified as new or experienced users. Adherence was measured by the Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire, treatment satisfaction by the Osteoporosis Patient Satisfaction Questionnaire (OPSAT) while general health-related and osteoporosis-specific quality of life were measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire and the Osteoporosis Assessment Questionnaire (OPAQ), respectively. The association of GI events with these outcomes was determined by covariate-adjusted regression analysis of least squares mean differences in the scores of treated patients with and without GI events. Resource utilization was measured as the number of physician visits over the past 3 months, and multivariate regression analysis was used to assess the association of GI events with the likelihood of a visit. RESULTS: The GI event profile, quality of life scores, and resource use were numerically similar in untreated and treated women. The rate of adherence among treated women was higher in experienced than in new users. As indicated by mean scores, experienced users had better quality of life and slightly higher treatment satisfaction and fewer physician visits than new users. Except for adherence in new users, all measures were similarly adversely affected by GI events in both new and experienced users. CONCLUSIONS: GI events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis.

Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers in progressive metastatic breast cancer.

Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with poor EFS and OS opposite to the negative or lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic tools in a larger patient cohort and in a longer follow-up study.

Correlating clinical manifestations with factor levels in rare bleeding disorders: a report from Southern India.

Data on the clinical manifestations of patients with clotting factor defects other than Haemophilia A, B and von Willebrand disease are limited because of their rarity. Due to their autosomal recessive nature of inheritance, these diseases are more common in areas where there is higher prevalence of consanguinity. There is no previous large series reported from southern India where consanguinity is common. Our aim was to analyze clinical manifestations of patients with rare bleeding disorders and correlate their bleeding symptoms with corresponding factor level. Data were collected in a standardized format from our centre over three decades on 281 patients who were diagnosed with rare bleeding disorders (fibrinogen, prothrombin, factor V (FV), FVII, FX, FXI, FXIII and combined FV or FVIII deficiency). Patients with liver dysfunction or those on medications which can affect factor level were excluded. All patients with <50% factor levels were included in this analysis. Patients were analysed for their salient clinical manifestations and it was correlated with their factor levels. The data shows that FXIII deficiency is the commonest and FXI deficiency is the rarest in Southern India. There was no significant difference in bleeding symptoms among those who were < or >1% factor coagulant activities among all disorders, except for few symptoms in FVII and FX deficiency. An international collaborative study is essential to find out the best way of classifying severity in patients with rare bleeding disorders.