Covid-19 presenting as isolated severe thrombocytopenia in an HIV-lymphoma survivor

Coronavirus disease has myriad manifestations and can present with predominantly extrapulmonary manifestations. We describe a 50-year-old man, a person living with HIV (PLHA), a non-Hodgkin lymphoma survivor, who presented with isolated severe thrombocytopenia. He was found to have immune-mediated thrombocytopenia, and showed excellent response to intravenous immunoglobulins.

The time required to diagnose and treat lung cancer in Delhi, India: an updated experience of a public referral center

Background: Delays that postpone the evaluation and management of malignancy may lead to considerable morbidity. The primary objective of this study was to assess the time required to diagnose and treat lung cancer at an Indian public referral center that predominantly serves lower-income patients. Methods: A review of patients diagnosed with lung cancer between January 2008 and December 2016 was completed. We computed the median time intervals and inter-quartile ranges between symptom onset, definitive diagnostic investigation, confirmed histologic diagnosis, and chemotherapy initiation. Median intervals were correlated with baseline demographics and disease characteristics using Kruskal-Wallis test. Results: One thousand, three hundred and-seventy patients were selected. A majority (94.5%) with non-small cell lung cancer were diagnosed with advanced disease. After developing symptoms, patients required 101 [56­168] days to undergo a definitive diagnostic study, 107 [60­173] days to confirm a diagnosis, and 126 [85­196.8] days to initiate treatment. Patients who were previously treated for tuberculosis required more time to receive chemotherapy compared to those who were not (187 [134­261.5] days vs. 113 [75­180] days, p < 0.0001). A specialty Lung Cancer Clinic was implemented in 2012, and the mean referrals per month increased nearly four-fold (p < 0.0001), but the time required to administer treatment was not shortened. Conclusion: Among lower-income Indian patients, the most prominent delays occur prior to diagnosis. Efforts should be directed toward encouraging physicians to maintain a high index of clinical suspicion and educating patients to report concerning symptoms as early as possible.

Micro RNAs and Non-Small Cell Lung Cancer

Non-small cell lung cancer is a major leading cause of cancer-related death and its late diagnosis/prognosis, accounting for the high rate of mortality. Presences of circulating microRNAs (miRNAs) in body fluids represent stable and reproducible biomarkers for several solid tumors, including non-small cell lung cancer. Micro RNAs have been categorized as oncogenic microRNAs and “tumor suppressor micro RNAs” and miRNAs activities may provide exciting opportunities for early cancer detection. There is an urgent need to find a less invasive and a more reliable biomarker which can increase the probability of early non-small cell lung cancer detection.

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study.

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Diagnostic potential of 16 kDa (HspX, α-crystalline) antigen for serodiagnosis of tuberculosis.

Background & objectives: Tuberculosis (TB) is a public health problem worldwide. Rapid and accurate diagnosis of tuberculosis is crucial to facilitate early treatment of infectious cases and to reduce its spread. The present study was aimed to evaluation of 16 kDa antigen as a serodiagnostic tool in pulmonary and extra-pulmonary tuberculosis patients in an effort to improve diagnostic algorithm for tuberculosis. Methods: In this study, 200 serum samples were collected from smear positive and culture confirmed pulmonary tuberculosis patients, 30 tubercular pleural effusions and 21 tubercular meningitis (TBM) patients. Serum samples from 36 healthy, age matched controls (hospital staff), along with 60 patients with non-tubercular respiratory diseases were also collected and evaluated. Humoral response (both IgG and IgA) was looked for 16 kDa antigen using indirect ELISA. Results: Sensitivity of detection in various categories of pulmonary TB patients ranged between 73.8 and 81.2 per cent. While in the extra-pulmonary TB samples the sensitivity was 42.8 per cent (TBM) and 63.3 per cent (tubercular pleural effusion). The test specificity in both the groups was high (94.7%). All of the non-disease controls were negative. Among non-tubercular disease controls, five patients gave a positive humoral response against 16 kDa. Interpretation & conclusions: Serodiagnostic tests for TB have always had drawbacks of suboptimal sensitivity and specificity. The antigen used in this study gave encouraging results in pulmonary TB only, while in extra-pulmonary TB (tubercular meningitis and tubercular pleural effusion), this has shown a limited role in terms of sensitivity. Further work is required to validate its role in serodiagnosis of TB especially extra-pulmonary TB.

A rare case of orbital apex syndrome with herpes zoster ophthalmicus in a human immunodeficiency virus-positive patient.

We report a rare instance of favorable outcome in orbital apex syndrome secondary to herpes zoster ophthalmicus (HZO) in a human immunodeficiency virus (HIV)-positive patient. The patient complained of pain and decrease in vision in one eye (20/640) for 2 weeks accompanied with swelling, inability to open eye, and rashes around the periocular area and forehead. The presence of complete ophthalmoplegia, ptosis, relative afferent pupillary defect, and anterior uveitis with decreased corneal sensation prompted a diagnosis of HZO with orbital apex syndrome. The enzyme-linked immunosorbent assay test and a low CD4 count confirmed HIV. Highly active antiretroviral therapy (HAART), systemic acyclovir, and systemic steroids were started. Visual acuity and uveitis improved within 10 days. By the end of the fourth week, ocular motility also recovered and the final visual acuity was 20/25. We highlight the role of HAART, used in conjunction with systemic steroid and acyclovir therapy, in improving the outcome.

Study of dihydropteroate synthase (DHPS) gene mutations among isolates of Pneumocystis jiroveci.

BACKGROUND & OBJECTIVES: Pneumocystis jiroveci (also known as P. carinii) causes fatal pneumonia in patients with AIDS and other immunocompromised patients. Co-trimoxazole (trimethoprim + sulphamethoxazole, TMP-SMZ) is the drug of choice for treatment and prophylaxis. Widespread use of sulpha medication has raised the possible selection of resistant P. jiroveci strains worldwide. Non-synonymous polymorphisms associated with sulpha resistance have been observed in P. jiroveci dihydropteroate synthase (DHPS) gene at codons 55 and 57. In view of this, we investigated mutation at DHPS locus amongst P. jiroveci isolates obtained at a tertiary care hospital in north India. METHODS: Microscopic examination of P. jiroveci in 69 clinical samples obtained from patients suspected to have P. carinii pneumonia (PCP), was performed by Grocott's Gomori methenamine silver and direct fluorescent antibody staining. Molecular studies were carried out by polymerase chain reaction (PCR) using major surface glycoprotein (MSG) as the target gene. Investigations for DHPS mutations were carried at specific 55th and 57th codon using PCR-RFLP (restriction fragment length polymorphism) assay. RESULTS: Microscopic examination detected P. jiroveci in four cases and MSG gene was amplified in five cases. Further, amplification of DHPS gene was successful in four of the five cases positive by MSG gene PCR. No point mutation was observed and all four isolates presented wild-type sequences at DHPS gene by RFLP analysis. INTERPRETATION & CONCLUSION: Although our findings suggest that in Indian subpopulation, point mutations in DHPS gene of P. jiroveci are not as common as in other parts of the developed world, further studies are needed.

Effect of change in symptoms, respiratory status, nutritional profile and quality of life on response to treatment for advanced non-small cell lung cancer.

INTRODUCTION: Quality of life (QOL), and pulmonary and nutritional parameters are important outcome measures during treatment of lung cancer; however, the effect of chemotherapy on these factors and their relationship with clinical response is unclear. METHODS: Patients with non-small cell lung cancer (NSCLC) were evaluated for symptom profile, nutritional status (using anthropometry), pulmonary functions by spirometry and six minute walk distance (6 MWD), and QOL using the WHO-QOL Bref 26 questionnaire, before and after chemotherapy. RESULTS: Forty-four patients were studied (mean (SD) age, 55 (10) years, 75% males). The majority (98%) had stage III or IV disease and 72% were current / ex-smokers with median pack-years of 27.0 (range, 0.5-90). Some 61% had a Karnofsky Performance Scale (KPS) 70 or 80. The commonest symptoms were coughing, dyspnea, chest pain, anorexia and fever (79%, 72%, 68%, 57% and 40%, respectively). The mean (SD) 6 MWD was 322.5 (132.6) meters. The mean (SD) percentage forced vital capacity (FVC %), and forced expiratory volume in one second (FEV1 %) were 64.7 (18.8) and 57.8 (19.4), respectively. The mean (SD) QOL scores for the physical, psychological, social, and environmental domains were 52.9 (20.5), 56.1 (17.9), 64.5 (21.8), 57.1 (16.6), respectively. Fourteen patients (32%) responded to chemotherapy. Non-responders had significantly higher baseline occurrence of fever, anorexia, and weight loss, higher pack-years of smoking and poorer KPS compared to responders. Overall, chemotherapy caused significant decline in the frequency of coughing, dyspnea, chest pain, fever, anorexia, weight loss, and improvement in hemoglobin and albumin levels. There was no significant improvement in pulmonary functions, nutritional status, or QOL scores after treatment. CONCLUSIONS: Lung cancer patients have a poor QOL. Although chemotherapy provides significant symptomatic benefit, this does not translate into similar benefit in respiratory and nutritional status or QOL. Patients with constitutional symptoms, higher smoking burden, and poor KPS are less likely to respond to chemotherapy. Management of NSCLC must include strategies to improve various aspects of QOL, nutritional status and pulmonary reserve to achieve comprehensive benefit.

Use of different primer directed sequence amplification by polymerase chain reaction for identification of Pneumocystis jirovecii in clinical samples.

BACKGROUND: Pneumocystis carinii pneumonia (PCP), caused by opportunistic agent Pneumocystis jirovecii (formerly, Pneumocystis carinii is one of the most serious respiratory infection in immunocompromised patients. AIM: The present study was conducted to compare polymerase chain reaction (PCR) assays targetting three different genes of Pneumocystis to study their application in its diagnosis. METHODS: One hundred and eighty (n = 180) clinical samples from 145 immunocompromised patients with clinical suspicion of PCP and 35 samples from control group of 30 immunocompetent individuals with respiratory infections other than PCP were prospectively examined for the presence of Pneumocystis jirovecii (P. jirovecii). All the samples were subjected to microscopic examination, one single [major surface glycoprotein, (MSG)] and two nested [mitochondrial large subunit ribosomal ribonucelic acid, (mtLSU rRNA) and internal transcribed spacer (ITS) region], polymerase chain reaction assays. RESULTS: Microscopic examination was positive in only six (n = 6) patients, whereas single round MSG PCR detected P. jirovecii deoxyribonucleic acid (DNA) in 16 cases. When the clinical samples were tested by mtLSU rRNA and ITS nested PCR assays, it was possible to detect seven additional cases of PCP, making it to a total of 23 cases. None of the clinical specimens in control group (n = 30) were positive by any of the above-mentioned techniques. Amongst the 81 bronchoalveolar lavage (BAL) samples tested, 16 were positive by MSG PCR, while 20 were positive by both nested, i.e., mtLSU rRNA and ITS PCR assays. Similarly, out of 50 sputum samples, only three were positive by MSG, seven by mtLSU rRNA and six by ITS nested PCR assays. CONCLUSION: It has been observed that MSG is relatively more sensitive when single round PCR assay is used for detection of human Pneumocystosis compared to the first (single) rounds of either ITS or mtLSU rRNA nested PCRs. However, the two nested PCRs using ITS and mtLSU rRNA have been found to be more sensitive. On comparison of two nested PCR assays, the results have been more or less comparable.

Small cell lung cancer: an update on therapeutic aspects.

Small cell lung cancer comprises approximately 20% of all lung cancers and continues to be a difficult management issue. More than two-thirds of cases present with extensive disease, which has spread beyond the himithorax and regional ipsilateral nodes. While response rates to chemotherapy are relatively high, durable responses are rare, and long-term survival rates are anecdotal. Although many attempts have been made to develop new therapies, a combination of etoposide with either cisplatin or carboplatin remains the most widely used first-line therapy for extensive disease. For those with limited disease, chemotherapy with concomitant radiotherapy (given with the first or second cycles of chemotherapy) is considered the standard of care. Over the last decade, several new drugs and targeted agents have been identified with the aim to improve outcome of this malignancy. In this review we highlight recent developments in the management of this tumour.