Platinum based doublet cross over therapy for advanced stage non small cell lung cancer? A better survival option

Platinum based doublet chemotherapy namely the cisplatin/carboplatin based etopiside or gemcitabine therapy forms the therapy of choice, for patients with advanced non small cell carcinoma of the lung. Here we report two cases were unusual cross over was done from gemcitabine-to cisplatin-doublet chemotherapy resulting in unexpectedly better clinical and radiological response

Primary pulmonary non hodgkin’s T cell lymphoma

A 55-year-old female presented with history of fever, dry cough and right sided chest pain of two months duration. Radiological examination revealed a soft tissue attenuated lesion involving right middle lobe. Immuno histochemical analysis leads to the diagnosis of Non Hodgkin’s T-cell Lymphoma. The rarity of this disorder and its good clinical and radiological response to chemotherapy prompted us to report this case

Swyer- James -MacLeod syndrome presenting as hemoptysis in an adult

Swyer-James/MacLeod syndrome is an uncommon disease with characteristic radiological feature of unilateral hyperlucency due to loss of pulmonary vasculature and air trapping. Typically, this disorder is diagnosed in childhood during evaluations for recurrent respiratory infections. Here, we report a case in a 30-year-old adult female who presented with dyspnoea, cough with expectoration and recurrent hemoptysis due to associated bronchiectasis. This case highlights the importance of computed tomography in the diagnostic workup of recurrent hemoptysis in pulmonary tuberculosis epidemic countries like India

Spontaneous Resolution of Massive Spontaneous Tubercular Pneumothorax

A 29-year-old female presented with complaints of fever and productive cough of three weeks duration. Pulmonary tuberculosis was diagnosed bacteriologically and she was prescribed antituberculosis drugs. During follow-up she developed massive pneumothorax, for which patient refused surgical management and was managed conservatively. After six months there was complete spontaneous resolution of pneumothorax. The unusual presentation and unexpected outcome prompted us to report this case

Parallel evolution in streptococcus pneumoniae biofilms

Streptococcus pneumoniae is a commensal human pathogen and the causative agent of various invasive and noninvasive diseases. Carriage of the pneumococcus in the nasopharynx is thought to be mediated by biofilm formation, an environment where isogenic populations frequently give rise to morphological colony variants, including small colony variant (SCV) phenotypes. We employed metabolic characterization and whole-genome sequencing of biofilm-derived S. pneumoniae serotype 22F pneumococcal SCVs to investigate diversification during biofilm formation. Phenotypic profiling revealed that SCVs exhibit reduced growth rates, reduced capsule expression, altered metabolic profiles, and increased biofilm formation compared to the ancestral strain. Whole-genome sequencing of 12 SCVs from independent biofilm experiments revealed that all SCVs studied had mutations within the DNA-directed RNA polymerase delta subunit (RpoE). Mutations included four large-scale deletions ranging from 51 to 264 bp, one insertion resulting in a coding frameshift, and seven nonsense single-nucleotide substitutions that result in a truncated gene product. This work links mutations in the rpoE gene to SCV formation and enhanced biofilm development in S. pneumoniae and therefore may have important implications for colonization, carriage, and persistence of the organism. Furthermore, recurrent mutation of the pneumococcal rpoE gene presents an unprecedented level of parallel evolution in pneumococcal biofilm development

Multispacer Sequence Typing for Mycobacterium tuberculosis Genotyping

Background: Genotyping methods developed to survey the transmission dynamics of Mycobacterium tuberculosis currently rely on the interpretation of restriction and amplification profiles. Multispacer sequence typing (MST) genotyping is based on the sequencing of several intergenic regions selected after complete genome sequence analysis. It has been applied to various pathogens, but not to M. tuberculosis. Methods and Findings: In M. tuberculosis, the MST approach yielded eight variable intergenic spacers which included four previously described variable number tandem repeat loci, one single nucleotide polymorphism locus and three newly evaluated spacers. Spacer sequence stability was evaluated by serial subculture. The eight spacers were sequenced in a collection of 101 M. tuberculosis strains from five phylogeographical lineages, and yielded 29 genetic events including 13 tandem repeat number variations (44.82%), 11 single nucleotide mutations (37.93%) and 5 deletions (17.24%). These 29 genetic events yielded 32 spacer alleles or spacer-types (ST) with an index of discrimination of 0.95. The distribution of M. tuberculosis isolates into ST profiles correlated with their assignment into phylogeographical lineages. Blind comparison of a further 93 M. tuberculosis strains by MST and restriction fragment length polymorphism-IS6110 fingerprinting and mycobacterial interspersed repetitive units typing, yielded an index of discrimination of 0.961 and 0.992, respectively. MST yielded 41 different profiles delineating 16 related groups and proved to be more discriminatory than IS6110-based typing for isolates containing M<8 IS6110 copies (P<0.0003). MST was successfully applied to 7/10 clinical specimens exhibiting a Cts <= 42 cycles in internal transcribed spacer-real time PCR. Conclusions: These results support MST as an alternative, sequencing-based method for genotyping low IS6110 copy-number M. tuberculosis strains. The M. tuberculosis MST database is freely available (http://ifr48.timone.univ-mrs.fr/MST_MTuberculosis/mst)

Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing.

Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity. A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay. Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4-14 laboratories. Six non-target viruses were detected by three or more laboratories. The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

ПЛЕВРАЛЬНИЙ ЕНДОМЕТРІОЗ: ГЕМОРАГІЧНИЙ ПЛЕВРАЛЬНИЙ ВИПІТ У 28-РІЧНОЇ ЖІНКИ З ПЕРВИННОЮ БЕЗПЛІДНІСТЮ (КЛІНІЧНИЙ ВИПАДОК)

Background. Endometriosis is defined as presence of endometrial glands outside the uterine cavity and it most commonly involves the structures within the pelvic cavity. Thoracic endometriosis syndrome usually presents as pneumothorax, hemoptysis, hemothorax or pulmonary nodules. Endometriosis presenting as hemorrhagic pleural effusion is rarely reported. Objectives. The aim of the study was to describe pleural endometriosis presenting as hemorrhagic pleural effusion and to insist on the role of medical thoracoscopy in making the diagnosis with the help of a case report. Methods. A case report of pleural endometriosis as a non-resolving hemorrhagic pleural effusion is presented. Results. A 28-years old female on treatment for her primary infertility presented with non-resolving bloody pleural effusion and she was on empirical anti-tubercular drugs for the last four months. Medical thoracoscopy revealed flat brownish grey plaques over the diaphragmatic pleura and the histology of pleural tissue revealed pleural endometriosis. She was initiated on gonadotropin releasing hormone-leuprolide and there was some clinico-radiological improvement. Conclusions. Thoracic endometriosis should be considered as one of the differentials for pleural effusion in female patient especially on treatment for infertility. Medical thoracoscopy should be the investigation of choice for evaluating pleural effusions before initiating empirical treatments.Вступ. Ендометріоз характеризується наявністю ендометрію поза порожниною матки і зазвичай він виявляється в органах малого тазу. Ектрагенітальна його форма – ендометріоз легень - зазвичай маніфестує у вигляді пневмотораксу, кровохаркання, гемотораксу або легеневих вузликів. Вкрай рідко зустрічаються повідомлення про ендометріоз легень з клінічними проявами геморагічного плеврального випоту. Мета. Метою дослідження було описати ендометріоз легень, що маніфестував як геморагічний плевральний випіт та показати важливість медичної торакоскопії у постановці діагнозу. Методи. Описано клінічний випадок рідкісної форми ендометріозу легень - геморагічного плеврального випоту, який не розсмоктувався. Результати. Представлено клінічний випадок 28-річної жінки, яка лікувалася з приводу первинного безпліддя, з геморагічним плевральним випотом, який не розсмоктувався. Через підозру на туберкульоз протягом останніх чотирьох місяців вона приймала призначені лікарем чотири протитуберкульозних препарати. Медична торакоскопія виявила плоскі коричнево-сірі бляшки над діафрагмальною плеврою, а гістологія плевральної тканини виявила ендометріоз плеври. Пацієнтці було призначено лейпроліду ацетат (синтетичний агоніст гонадотропін-рилізинг гормону), після чого спостерігалося клініко-рентгенологічне покращення. Висновки. При проведенні диференціальної діагностики плеврального випоту у пацієнток, особливо при лікуванні безпліддя обов’язково слід розглядати ймовірність ендометріозу легень. Медична торакоскопія повинна бути методом вибору при оцінці плеврального випоту перед початком емпіричного лікування