Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.

Treatment Response to Neoadjuvant Therapy in Squamous Esophageal Cancer-Correlation Between Metabolic Response and Histopathology.

PURPOSE: Esophageal cancer is among the leading causes of cancer-related mortality worldwide. Patients presenting with localized and loco-regionally advanced cancer without distant metastases have reasonable survival with multimodality management. Adequate and comprehensive staging is the backbone for proper selection of patients fit for curative treatment. Positron emission tomography (PET) in combination with contrast-enhanced computed tomography (CECT) is utilized as the standard staging modality. Multimodality treatment has been able to achieve evaluable tumor responses including pathological complete response (pCR). It is, therefore, necessary to understand whether the impact of neoadjuvant therapy can be evaluated on imaging, i.e., standardized uptake value (SUV) on PET scan done for response assessment and if this can be correlated with histopathological response and later, with survival. Squamous cell carcinoma (SCC) is more common globally and in the Indian subcontinent; hence, we chose this subgroup to evaluate our hypothesis. METHODS: This is a single institution, retrospective study. Out of the 1967 patients who were treated between 2009 and 2019, 1369 (78.54%) patients had SCC. Out of these, 44 received NACTRT, whereas 1325 received NACT followed by curative surgery. The standardized uptake value (SUV) of 18-fluorodeoxyglucose was recorded during pre- and post-neoadjuvant treatment (NAT) using positron emission tomography (PET). The histopathology of the final resection specimen was evaluated using the Mandard tumor regression grade (TRG) criteria with response being graded from 0 to 5 as no residual tumor (NRT), scanty residual tumor (SRT), and residual tumor We attempted to find a cut-off value of the post neoadjuvant SUV of the primary tumor site which correlated with achievement of better histopathological response. RESULTS: Out of 1325 patients of SCC esophagus who underwent surgery, 943 patients had available data of TRG, and it was categorized into the 0-2 category which had 325 patients (34.5%) and 3-5 category, 618 patients (65.5%). The SUV was taken only from the PET scans done at our institution, so as to achieve a more homogenous cohort, and this was available for 186 patients, 151 from the NACT group and 35 from the NACTRT group. The ROC method was used to find the cut-off for SUV (5.05) in the NACT cohort, which depicted significant difference in the outcome. Out of these, 93 patients who underwent NACT had SUV > 5.05 and 58 had SUV < 5.05. It was found that the subjective and objective histopathological scores correlated at a p value of < 0.0001. Specifically, the majority of cases with SRT tended to be in the 3-5 category of TRG, whereas cases with NRT are predominantly in the 0-2 category. In the ≥ 5.05 category of SUV, there were 76 cases with SRT. In the NACT cohort, the < 5.05 category of SUV, there are 26 cases with SRT and 32 cases with NRT. Among cases with SRT, 74.5% had SUV ≥ 5.05, while 25.5% had SUV < 5.05. Among cases with NRT, 34.7% had SUV ≥ 5.05, while 65.3% had SUV < 5.05 (p value 0.007). No significant association was found in the radio-pathological correlation in the NACTRT group. CONCLUSION: Our study confirms the correlation of post neoadjuvant chemotherapy PET SUV with histopathological response, the cut-off of SUV being 5.05 in our cohort. This confirms the predictive value of FDG PET as demonstrated in other studies. Furthermore, its prognostic value with respect to survival has been verified in multiple other studies. With larger scale randomized studies, we may be able to identify the group of patients who have borderline operability anatomically as well as physiologically, where alternative treatment regimens may be indicated to improve outcomes.

Influence of stocking density and environmental factors on the expression of insulin-like growth factors in cage-reared butter catfish (Ompok bimaculatus, Bloch 1794) within a large reservoir ecosystem.

In vertebrates, insulin-like growth like factors (IGFs) play an important role in growth and other physiological processes. The GH-IGF axis is considered a valuable tool to monitor fish growth performance. Herein, we report the molecular characterization of igf-1, igf-2, and ß-actin transcripts and relative expression of igf-1 and igf-2 in the liver and muscle tissue of cage-reared butter catfish, Ompok bimaculatus, in response to different stocking densities (T1, 15 fingerlings m-3; T2, 25 fingerlings m-3; and T3, 35 fingerlings m-3) over 180 days of culture duration. The length of the partial amplified transcript sequence of Obigf-1, Obigf-2, and Obß-actin was 325, 438, and 924 bp, respectively. Phylogenetically, Obigf-1 and Obigf-2 were closely clustered with catfishes, viz., Clarias magur, Bagarius yarrelli, and Silurus asotus. The expression of igf-1 was significantly downregulated in the liver at higher densities after 120 days as biomass in the cages increased, while igf-2 expression did not change with the stocking densities over the culture period. Cortisol concentration was significantly elevated in T3 groups post 150 days of the culture period and correlated negatively with the expression of igf-1 (p < 0.05) and igf-2 (p > 0.05). Environmental parameters, pH, TDS, hardness, conductivity, and alkalinity showed a significant positive correlation with hepatic IGF expression. Our study indicates that the liver-derived igf-1 plays a more important role in the regulation of growth in response to culture density in the species studied, and thus, igf-1 can be used effectively as a biomarker for growth. Furthermore, this study will help in planning a proper harvest schedule and optimize the culture practices of O. bimaculatus in an open water cage system.

Robotic esophagectomy and 3-field lymphadenectomy with intraoperative nerve monitoring.

The standard of care for esophageal malignancies has evolved over the years from open transthoracic esophagectomy to a minimally invasive approach due to the reduction in surgical trauma and significant impact on postoperative outcomes. Minimally invasive approaches include video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery. These minimally invasive approaches have an attendant learning curve that early-career surgeons are required to negotiate before achieving proficiency in the procedure. Recurrent laryngeal nerve injury is a particularly significant problem, especially in the presence of enlarged supracarinal lymph nodes, which mandate a 3-field lymphadenectomy. With technological advances and the use of intraoperative nerve monitoring, iatrogenic nerve injury can at best be avoided or at least be recognized, and corrective measures can be undertaken to reduce postoperative morbidity. In this video tutorial, we demonstrate a standard robot-assisted esophagectomy and a 3-field lymphadenectomy with the use of intraoperative nerve monitoring followed by an esophagogastric anastomosis with the triangulating stapling technique.

Video-assisted mediastinoscopic lymphadenectomy (VAMLA): A video vignette.

Mediastinal staging in potentially resectable non-small cell lung cancer is of paramount importance since it impacts the survival of the patient. With increasing nodal stage, survival was noted to precipitously decline. Nodal status also determined the use of neoadjuvant/adjuvant therapy and other treatment modalities. Various methods of obtaining lymphatic tissue from the mediastinum for staging purposes have been described in the literature, although mediastinoscopic lymph node evaluation remains the gold standard. Endoscopic methods of mediastinal staging, like the endobronchial ultrasound guided and esophageal ultrasound guided fine-needle aspiration techniques, although minimally invasive, provide the highest levels of accuracy when used in conjunction with surgical mediastinal staging. Video-assisted mediastinoscopic lymphadenectomy (VAMLA) provides clear advantages, as far as ergonomics and training are concerned, over conventional mediastinoscopy. Access to stations 2R, 2L, 4R, 4L, and 7 is feasible with VAMLA. In this video vignette, we present the step-by-step technique of a standard VAMLA, with an overview of relevant anatomical relationships, for the effective and safe clearance of lymph node stations for the purposes of staging and defining appropriate therapy.

Uniportal VATS left lower lobectomy: Fissure first technique.

This video tutorial describes a left lower lobectomy performed by the uniportal approach. A single 2-cm incision in the lateral chest wall is used as the utility port. The procedure begins with division of the inferior pulmonary ligament and isolation of the inferior pulmonary vein. This patient has densely adherent interlobar nodes, which are then dissected to demonstrate the interlobar pulmonary artery. Then we proceed to divide the anterior part of the fissure after identifying and safeguarding the lingular branches of the pulmonary artery. This step is followed by the division of the posterior part of the fissure after identification of the posterior branches of the pulmonary artery to the upper lobe. Then we identify the basilar trunk and divide it using endostaplers. Other branches of the interlobar artery are clearly identified, and the apicobasal artery is taken separately. This is followed by division of the inferior pulmonary vein and a systematic mediastinal nodal dissection.

Environmental parameters and stocking density influence growth, feed utilization and economics of butter catfish, Ompok bimaculatus (Bloch, 1794) production in floating net cages in a large tropical reservoir, India.

An experiment was conducted to study the influence of environmental parameters and stocking density on growth, survival, feed utilization, and economic feasibility of a high value butter catfish, Ompok bimaculatus in floating cages in a large tropical reservoir of India for 180 days. The fingerlings (11.44 ± 1.33 cm; 8.05 ± 3.27 g) were stocked at three stocking densities, viz., 15, 25 and 35 fingerlings m-3 in GI cages (32m3) in triplicates. Commercial floating pellets were fed to fish at 5-3% of fish biomass. The results indicated that the fishes at the lowest stocking density of 15 fingerlings m-3 had significantly higher (p < 0.05) growth in relation to weight gain percentage (717.67 ± 39.10) and specific growth rate (1.14 ± 0.05). Survival percentage was also significantly higher (p < 0.01) at lower stocking densities compared with 35 fingerlings m-3. Similarly, the feed conversion efficiency (0.423 ± 0.025), protein efficiency ratio (1.37 ± 0.15) and feed conversion ratio (FCR) (2.37 ± 0.16) were significantly better at density of 15 fingerlings m-3. The fish growth and feed utilization efficiency did not vary significantly (p > 0.05) between stocking densities of 15 fingerlings m-3 and 25 fingerlings m-3. The condition factor was insignificantly higher at lower densities and its values close to 1 indicated congeniality of reservoir ecosystem for cage culture of the species. The coefficient of variation of weight was significantly higher (24.19 ± 1.20) at 35 fingerlings m-3. The highest economic gains in terms of benefit cost ratio (1.77) were achieved at the lowest stocking density. The present study indicated better growth and economic returns at lower stocking densities of 15-25 fingerlings m-3. The nutrient load and plankton abundance were higher at culture site, however, did not vary significantly from reference sites throughout the culture period. Although most of the environmental parameters showed significant seasonal variations, dissolved oxygen showed significant positive relation (r = 0.86) with the growth of the fish. This is the first study reporting feasibility of cage culture of this highly renumerative species in open waters. The cage culture of this species will not only ensure better economic returns to the marginal cage farmers but will aid in the conservation of this species in natural ecosystem. Being a low volume high value species, the impact on environment will be less compared with high volume low value species. This study will serve as baseline for standardization of its grow-out protocol in cages and will be a step towards much needed species diversification for sustainable small scale cage farming in tropical reservoirs of Asia.

Catalyst-controlled positional-selectivity in C-H functionalizations.

C-H bonds are ubiquitous in organic molecules and typically these bonds are chemically indistinct from each other and it would be highly advantageous for a synthetic chemist to have the ability to choose which C-H bond is functionalized in a given molecule. A controlled and positional-selective C-H bond functionalization is still a prominent goal in this area. With recent developments in transition metal-catalyzed regiodivergent C-H functionalizations, a switch in regioselectivity between two reactive sites within a given substrate is possible under catalytic control, and has profoundly impacted synthetic strategies. Switching site-selectivity within the same or similar precursors represents a great opportunity and challenge in altering the C-H functionalization from one reactive site to other by changing the choice of the catalytic system having a different mechanistic approach. This review discusses the potential and most common approaches employed in tweaking the catalytic systems to alter the positional-selectivity of C-H bond activation.

Prospective Evaluation of Surgical Outcome After Transoral CO2 Laser Resection of Potentially Malignant and Early Oral Malignancy.

A prospective observational study was done at the Regional Cancer Centre, Thiruvananthapuram, a tertiary referral center for cancer care in India with an aim to assess the surgical outcomes of CO2 laser resection of oral lesions in terms of operative time, blood loss, hospital stay, postoperative pain, time to re-epithelization, pathological margins achieved and the postoperative scar. The excision was performed in 30 patients with a diagnosis of either potentially malignant lesions (leucoplakia, erythroplakia) or early cancers, i.e., carcinoma in situ or T1/T2 squamous cell carcinoma of the anterior oral cavity (tongue, buccal mucosa), adhering to standard oncological principles, and the resultant defect was left for secondary healing.

One Substrate, Two Modes of C-H Functionalization: A Metal-Controlled Site-Selectivity Switch in C-H Arylation Reactions.

A unique site-selectivity switch has been achieved in the ruthenium-catalyzed C-H arylation reaction of N-acetyl-1,2-dihydroisoquinolines. This metal-mediated switch is antipodal to the previous report on the palladium-mediated C-4 C-H arylation on the same substrate. Mechanistic details reveal interesting aspects of the reaction pathway, and kinetic studies bring out the difference in the modes of C-H activation adopted by the two catalytic systems.

Gossypiboma: An Unusual Presentation as Perforation and Intraluminal Migration.

Gossypiboma is a mass formed around cotton material acting as foreign body in visceral cavity. In our study, we present a case of gossypiboma following open cholecystectomy. A surgical sponge left in the peritoneal cavity following cholecystectomy, caused inflammatory reaction, perforation and intraluminal migration. It is a relatively rare presentation. This patient underwent emergency laparotomy with Billroth II anastomosis and sponge removal.

Heteroatom-Guided, Palladium-Catalyzed, Site-Selective C-H Arylation of 4H-Chromenes: Diastereoselective Assembly of the Core Structure of Myristinin†B through Dual C-H Functionalization.

A highly site-selective, heteroatom-guided, palladium-catalyzed direct arylation of 4H-chromenes is reported. The C-H functionalization is driven not only by the substituents and structure of the substrate but also by the coupling partner being used. The diastereoselective assembly of the core structure of Myristinin B has been achieved by using a dual C-H functionalization strategy for regioselective direct arylation.

Ruthenium-catalyzed heteroatom-directed regioselective C-H arylation of indoles using a removable tether.

A new approach to C-2 arylated indoles has been developed by utilizing a ruthenium-catalyzed, heteroatom-directed regioselective C-H arylation. The reaction is highly site-selective and results in very good yields. The highlight of the work is the use of a removable directing group and compatibility of the catalytic system with halogen functional groups in the substrates.

Temperature induced morphological transitions from native to unfolded aggregated States of human serum albumin.

The circulatory protein, human serum albumin (HSA), is known to have two melting point temperatures, 56 and 62 °C. In this present manuscript, we investigate the interaction of HSA with a synthesized bioactive molecule 3-pyrazolyl 2-pyrazoline (PZ). The sole tryptophan amino acid residue (Trp214) of HSA and PZ forms an excellent FRET pair and has been used to monitor the conformational dynamics in HSA as a function of temperature. Molecular docking studies reveal that the PZ binds to a site which is in the immediate vicinity of Trp214, and such data are also supported by time-resolved FRET studies. Steady-state and time-resolved anisotropy of PZ conclusively proved that the structural and morphological changes in HSA mainly occur beyond its first melting temperature. Although the protein undergoes thermal denaturation at elevated temperatures, the Trp214 gets buried inside the protein scaffolds; this fact has been substantiated by acrylamide quenching studies. Finally, we have used atomic force microscopy to establish that at around 70 °C, HSA undergoes self-assembly to form fibrillar structures. Such an observation may be attributed to the loss of α-helical content of the protein and a subsequent rise in ß-sheet structure.

Palladium catalyzed, heteroatom-guided C-H functionalization in the synthesis of substituted isoquinolines and dihydroisoquinolines.

A new approach for the functionalization of C-4 of isoquinolines is reported. The method utilizes palladium catalyzed, hetero-atom guided (or electrophilic metalation) direct arylation via regioselective C-H functionalization of dihydroisoquinolines.

Heteroatom-guided, palladium-catalyzed regioselective C-H functionalization in the synthesis of 3-arylquinolines.

A new approach for the regioselective functionalization of the C-3-position of quinolines is described. The method utilizes heteroatom guided regioselective C-3 palladation followed by arylation via transmetalation with aryl boronic acids to yield 3-aryl-N-acyl-1,2-dihydroquinolines. In a one-pot sequence, N-deacylation followed by aromatization leads to important 3-arylquinolines in good yields.

A new species of Gauthieromyces and range extensions for other Harpellales to India.

One species of each of five genera of Harpellales--Gauthieromyces, Harpella, Legeriomyces, Stachylina and Zygopolaris--are reported for the first time from India. Gauthieromyces indicus is described from the hindguts of Baetis sp. nymphs. The new species is distinguished from the only other species, G. microsporus Lichtw., by having a greater number of and smaller generative cells per fertile branchlet with smaller trichospores that bear fine, entangled appendages. Occurrence of these fungi in India supports the observation that some genera and species of Trichomycetes are widespread but with apparent disjunct distributions.