Single-nucleotide polymorphisms of nucleotide excision repair genes and their association with overall survival in North Indian lung cancer patients treated with platinum-based doublet chemotherapy.

Background: The aim of the study is to understand the association of Nucleotide excision repair (NER) inter-genetic polymorphic combinations with overall survival (OS) in lung cancer as well as its histological subtypes in the North Indian population. Materials and Methods: Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. For survival analysis, the univariate Kaplan-Meier and multivariate Cox regression model were applied. Recursive partitioning method, survival analysis tree was applied to study unfavorable genotypic combinations in NER single-nucleotide polymorphisms. Results: Combinatorial studies suggested no association between polymorphic combinations of NER genes and OS in lung cancer patients. When stratified as per lung cancer histological subtypes, adenocarcinomas patients with XPG 670 and XPC 499 polymorphism a significant increase in OS in combined heterozygous and mutant genotype with a lower hazardous ratio (Hazard Ratio1 (HR) = 0.20; P = 0.004). Small-cell lung carcinoma (SCLC) patients with XPF 11985A>G and XPD Arg156Arg polymorphism showed a 4-fold hazard ratio among heterozygous genotype (HR1 = 4.84; P = 0.007) where no significant results are obtained in patients suffering from squamous cell carcinoma histological subtypes. STREE showed XPG Asp1104His (W), XPD Lys751Gln (H + M), XPF Arg415Gln (H + M) genotype was associated with a lower hazard ratio (P = 0.0007) showing survival of 11.6 months when compared with the reference (median survival time = 3.52). Conclusion: It can be concluded that SCLC patients with polymorphic combinations of the NER pathway were associated with a higher risk of mortality. STREE depicted the association of NER polymorphic combinations with a lower hazard ratio predicting them to be a good prognostic factor for lung cancer.

Proximal Interphalangeal Joint Arthroplasty Using the Wide-Awake Local Anesthesia No Tourniquet Technique.

BACKGROUND: Proximal interphalangeal joint (PIPJ) osteoarthritis is a common condition that results in pain, stiffness, and loss of function in the affected hand. Proximal interphalangeal joint arthroplasty is an effective treatment option when conservative methods have failed. The wide-awake local anesthesia no tourniquet (WALANT) technique to perform surgery carries advantages such as lack of tourniquet discomfort, reduces the staffing and costs associated with anesthesia and sedation, and allows faster recovery. We aimed to determine whether the WALANT technique was safe and effective in the context of PIPJ arthroplasty. METHODS: Patients were enrolled retrospectively from January 2015 to October 2020 by examining operating theater records and surgeon logbooks. Electronic patient records were examined to obtain patient data. Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires and Visual Analog Scale (VAS) for pain were sent by post to patients-with a separate DASH and VAS for each digit operated on. RESULTS: Twenty-nine PIPJ arthroplasties were carried out using WALANT technique by 3 different surgeons all using the dorsal approach. All cases were successfully carried out as day-case procedures. There was a significant correlation with increasing VAS and increasing DASH score. Proximal interphalangeal joint arthroplasty improved range of motion from 28.9 ± 5.5° to 79.4 ± 13.3° (P < .0001). Two cases developed complications related to surgery. CONCLUSIONS: Our study is the first to report the use of WALANT to perform PIPJ arthroplasty, and shows comparable results with traditional methods. Larger, multicenter prospective trials are required to determine the efficacy of this technique and to quantify its economical benefit.

Effectiveness of Convalescent Plasma Therapy in Moderate to Severely Ill Covid-19 Patients.

Convalescent plasma therapy, a classic adaptive immunotherapy used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with acceptable efficacy and safety in the past. Convalescent plasma therapy was taken into consideration in management of COVID 19 disease during the initial days of pandemic but was withdrawn later due to its doubtful beneficial role. This study aims to explore the beneficial role of convalescent plasma and to determine whether convalescent plasma therapy holds a second chance in treating SARS COV-2. MATERIAL: This cross-sectional observational study includes 82 cases of moderate to severely ill COVID 19 patients who received convalescent plasma therapy and 41 controls who didn't. Regular monitoring of TLC, P/F ratio, N/L ratio inflammatory markers, respiratory rate, oxygen saturation, ABG and radiological imaging was done for comparative analysis. OBSERVATION: In case group 39 patients (47.56%) were on oxygen mask, 17 patients (20.73%) on NIV, 9 Patients on NRM (10.97%), 16 patients (19.51%) on room air, 1(1.21%) on HFNC initially. After 7th day of convalescent plasma therapy 49 patients (59.75%) were on room air which suggests significant improvement in mode of ventilation in case group as compared to control group. Mean respiratory rate in case group was 30.46 CPM initially and 24.7 CPM on day 7th of plasma therapy which is statistically significant. CONCLUSION: Plasma therapy is effective if given in early stage of disease and convalescent plasma donors having adequate antibody titre.

The utilization of fluorescent cholangiography during robotic cholecystectomy at an inner-city academic medical center.

In recent years, fluorescent cholangiography using Indocyanine green (ICG) dye has been used to aid identification of structures during robotic cholecystectomy. We sought to compare cholecystectomy with ICG dye versus laparoscopic cholecystectomy at an inner-city academic medical center. Between January 2013 and July 2016, we identified 287 patients of which 191 patients underwent laparoscopic cholecystectomy and 96 patients underwent robotic cholecystectomy with ICG dye. Preoperative risk variables of interest included age, sex, race, body mass index (BMI), and acute cholecystitis. Primary outcome of interest was conversion to open procedures while secondary outcome was length of stay. The two groups were similar in their BMI (31.98 vs. 31.10 kg/m2 for the laparoscopic and robotic, respectively, p = 0.32). The laparoscopic group had a greater mean age compared to the robotic group (47.77 vs. 43.61 years, p = 0.04). There was no significant difference in sex and emergency surgery between the two groups. Fewer open conversions were found in the robotic than the laparoscopic group [2 (2.1%) vs. 17 (8.9%), p = 0.03]. In multiple logistic regression, robotic cholecystectomy with ICG also showed a lower risk of conversion compared to laparoscopic cholecystectomy, but the difference did not reach statistical significance (OR 0.42, 95% CI 0.11-1.65, p = 0.22). ICG fluorescent cholangiography during robotic cholecystectomy may contribute to proper identification of biliary structures and may reduce the rates of open conversion. The preliminary results of fewer open conversions are promising. Further studies with a large randomized prospective controlled study should be taken for further evaluation.

Increasing use of CTPA for the investigation of suspected pulmonary embolism.

OBJECTIVES: Pulmonary embolism (PE) is a frequently suspected life-threatening condition that often presents with non-specific signs and symptoms. There is concern that increased availability of computerized tomography pulmonary angiogram (CTPA) is resulting in overuse in the diagnostic workup of patients presenting with cardio-respiratory symptoms. We therefore aimed to determine whether use of CTPA was increasing over time within our institution, with a consequent decrease in the diagnostic yield of PE. Furthermore, we investigated the frequency of alternative (non-PE) pathological findings revealed by CTPA. METHODS: All patients who underwent CTPA in the first 15 days of eight consecutive years were enrolled retrospectively. Radiology reports and online medical records were examined. In addition, the rates of incidental PE from patients undergoing CT chest for non-suspected PE indications were also examined. RESULTS: An increasing use of CTPA was confirmed (p = 0.04). Despite this, the diagnostic yield of PE also increased (p = 0.03). Similarly, increasing numbers of patients underwent CT chest for non-PE indications, but in this group the rate of incidental PE remained static (~3.4%). In CPTA investigations that were negative for PE, common alternative findings were consolidation, pleural effusion and emphysema, with only 16.7% showing no abnormality. CONCLUSION: Although CTPA use is increasing, so is the diagnostic yield of PE. In contrast, the rate of incidental PE in those undergoing a CT chest scan for non-PE diagnosis remains relatively low and stable. This suggests that our observed increased use of CTPA is clinically appropriate.

Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation.

RATIONALE: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. OBJECTIVES: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. METHODS: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. MEASUREMENTS AND MAIN RESULTS: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. CONCLUSIONS: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans.

Assays of eosinophil apoptosis and phagocytic uptake.

Eosinophilic inflammation plays an important role in driving a variety of inflammatory and allergic conditions. Delineating the mechanisms by which these terminally differentiated granulocytes undergo programmed cell death (apoptosis) and their subsequent clearance by surrounding phagocytes are central to understanding disease pathogenesis and development of novel pharmacological agents. Dysregulation of the processes of either apoptosis or phagocytosis can result in chronic inflammation and disease progression due to either increased eosinophil life-span or cell necrosis with loss of cell membrane integrity and release of toxic intracellular mediators. A variety of in vitro methods have therefore been developed to understand these mechanisms in isolated primary human eosinophils. Here we describe the key assays used to study eosinophil apoptosis and the intracellular signalling pathways involved as well as phagocytic clearance of these cells.

Sialofucosylated podocalyxin is a functional E- and L-selectin ligand expressed by metastatic pancreatic cancer cells.

Selectin-mediated interactions in the vasculature promote metastatic spread by facilitating circulating tumor cell binding to selectin-expressing host cells. Therefore, identifying the selectin ligand(s) on tumor cells is critical to the prevention of blood-borne metastasis. A current challenge is to distinguish between structures expressed by circulating tumor cells that can bind selectins in vitro from the functional ligands whose depletion suppresses selectin-dependent binding under flow in vivo. Interestingly, podocalyxin (PODXL), which can bind E- and L-selectin, is upregulated in a number of cancers, including those of the breast, colon, and pancreas. In this work, we show that metastatic pancreatic cancer cells overexpress PODXL compared with nonmalignant pancreatic epithelial cells. We further demonstrate via tissue microarray that 69% of pancreatic ductal adenocarcinomas stain positive for PODXL. In cases of focal expression, positive staining is restricted to the invasive front of primary tumors. By combining immunoblot, immunodepletion, short-hairpin RNA-mediated gene silencing, and flow-based adhesion assays, we evaluated the functional role of sialofucosylated PODXL in selectin-mediated adhesion under flow. Our data indicate that sialofucosylated PODXL is a functional E- and L-selectin ligand expressed by metastatic pancreatic cancer cells, as specific depletion of this molecule from the cell surface significantly interferes with selectin-dependent interactions. Cumulatively, these data support a correlation between sialofucosylated PODXL expression and enhanced binding to selectins by metastatic pancreatic cancer cells and offer additional perspective on the upregulation of PODXL in aggressive cancers.

Giant primary pulmonary fibrosarcoma.

A rare case of primary fibrosarcoma in a 48-year-old male is described who presented with a huge pulmonary mass on the left side. The diagnosis was established on fine needle aspiration cytology (FNAC) and percutaneous transthoracic lung biopsy, supported by immuno-histochemistry.

Recurrent haemoptysis following sildenafil administration.

Sildenafil is widely used in the treatment of male erectile disorder and is generally well-tolerated. Its adverse effects are reported to be mild and include flushing, headache, dyspepsia and visual disturbances. We document a case of recurrent haemoptysis observed soon after self administration of sildenafil in a 38-year-old male with no other causative factors. The episodes of haemoptysis stopped following stoppage of sildenafil.

Tuberculosis of the middle ear with post auricular abscess.

A case of tuberculous otitis media with post auricular abscess is being described in a 14-year-old female patient in view of its rare occurrence. The diagnosis was made on demonstration of acid fast bacilli (AFB) in the ear discharge and characteristic cytological features of post auricular abscess aspirate.

A case of pulmonary carcinoid tumor with concomitant tuberculosis.

The simultaneous occurrence of pulmonary carcinoid tumor and tuberculosis is very rare. A case of pulmonary carcinoid tumor is described in a 35-year-old male patient who had concomitant ipsilateral pulmonary tuberculosis. The importance of dual pathological diagnosis in clinical practice is also emphasized.

Diphenylhydantoin (phenytoin)-induced chronic pulmonary disease.

Drug-induced respiratory diseases are difficult to diagnose and therefore usually not identified, probably underestimated and under-reported. We report a case of diphenylhydantoin/phenytoin-induced chronic pulmonary disease in a 62-year-old male patient presenting with progressive dyspnea, eosinophilia, and pulmonary abnormalities. The importance of drug history in clinical history-taking and early diagnosis of drug-induced respiratory diseases is emphasized so as to prevent permanent pulmonary damage.

Clinical profile of patients having pulmonary tuberculosis and renal amyloidosis.

OBJECTIVES: This study was planned to define the clinical profile of pulmonary tuberculosis (PTB) patients having renal amyloidosis, to identify the factors responsible for development of amyloidosis, to detect the time period between onset of amyloidosis and PTB, and analyze clinical features of amyloidosis in PTB patients for early diagnosis and timely assessment. MATERIALS AND METHODS: Patients of PTB having pedal edema, proteinuria, and grossly diseased kidneys on ultrasound abdomen were subjected to renal biopsy and appropriate biochemical investigations. Clinical profile of biopsy proven amyloidosis cases was analyzed. RESULTS: There were 43 patients (32 males, 11 females, age range 20-65 years) having PTB with pedal edema, proteinuria, and renal medical disease on abdominal ultrasound where amyloidosis was confirmed by renal biopsy. The total duration of illness ranged from two months to seven years (mean 2.25 years) and was less than five years in 93% patients. All patients had significant proteinuria. Nephrotic syndrome was seen in 23, hypertension in 19, hypoalbuminemia in 33, hypercholesterolemia in 29, and deranged renal functions in 32 patients. Ninety percent patients had moderate to far advanced pulmonary lesions on chest radiography with smear positivity in 21 patients. CONCLUSIONS: Renal amyloidosis is an important complication of PTB and should be suspected clinically in patients presenting with a triad of pedal edema, proteinuria, and medical renal disease on ultrasound. Contrary to general belief, renal amyloidosis may occur in PTB patients having disease for relatively shorter duration, and even if adequately treated.

Tuberculosis of oral cavity.

Tuberculous involvement of oral cavity is very rare. A 34-year-old male presented with non-healing ulcer at upper lip mucosa. Biopsy from ulcer revealed tuberculous lesion. He also had asymptomatic pulmonary tuberculosis diagnosed during work up for primary site of the disease.

Massive haemothorax in asymptomatic pseudocyst pancreas.

The case of a 35-year old man who presented with massive left sided haemothorax as a complication of an asymtomatic pancreatic pseudocyst is descibed. The diagnosis was confirmed by very high amylase content of the pleural fluid. The complications of pancreatitis and pancreatic pseudocyst are also briefly discussed. Haemothorax represents an unusual pulmonary complication of pseudocyst pancreas and should be considered in the differential diagnosis of pleural fluid collection in pancreatitis.