Needle necropsy in AIDS

The value of autopsy in understanding the natural course of any disease is beyond any argument. The reluctance of pathologists to perform autopsy in HIV infected cadavers is justified due to the risks involved to the prosector and the morgue attendants. A relative low risk needle necropsy protocol is proposed using fine needle aspiration cytology, tru-cut biopsies and microbiological examination. Diagnosis could be offered in all the forty-four needle necropsies performed. Disseminated tuberculosis in 18/44 (40.9%) cases, disseminated cryptococcosis in 12/44 (27.2%) cases, poly-microbial infections in 27.2% cases and non-Hodgkin's lymphoma in 9% cases were detected in the study. Infectious agents like Histoplasma capsulatum, Isospora belli, tachyzoites of Toxoplasma gondii, Candida sp and Cryptococcus sp could be demonstrated in the samples obtained in the study. Lack of material for study of gross pathology, inaccessibility of deep-seated lesions and risk of needle stick injury to the prosector though low are the limitations of this procedure.     

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.     

Impact of cytogenetics on the outcome of autotransplantation for acute myeloid leukemia in first remission: is the benefit of intensive pretransplant therapy limited to patients with good karyotypes?

A total of 81 adults with acute myeloid leukemia (AML) (47% favorable karyotypes) were autografted in first remission after melphalan-total body irradiation, having received 0 (n=7), 1 (n=19), 2 (n=51), or 3 (n=4) consolidation chemotherapy cycles before harvest. The cumulative 5-year incidences of relapse and transplant-related mortality were 37 and 17%, respectively. The actuarial 5-year probability of disease-free survival (DFS) was 46%. In Cox analysis, favorable karyotypes, increasing numbers of consolidation cycles (0 vs > or =1 or 1 vs >1), and higher nucleated cell doses were associated with lower relapse rates and higher DFS. Patients with favorable karyotypes benefited from every additional cycle of consolidation therapy (0 vs > or =1 as well as 1 vs >1). Among patients with other karyotypes, while the benefit of one cycle of consolidation was clear (0 vs > or =1), there was no obvious beneficial impact of further consolidation therapy (1 vs >1). Administration of consolidation chemotherapy prior to harvest is essential in AML. While it is possible to enhance the benefit of consolidation with favorable karyotypes by delivering two cycles, its usefulness is limited in others. In them, it may be worthwhile exploring alternatives not normally used in AML (eg high-dose cyclophosphamide) that could have antileukemic effects while permitting mobilization of stem cells.     

Collection of peripheral blood stem cells in newly diagnosed myeloma patients without any prior cytoreductive therapy: the first step towards an 'operational cure'?

We have shown that primary therapy with non-myeloablative (140 mg/m(2)) high-dose melphalan (HDM) without hematopoietic support results in high response rates in untreated myeloma and very long-term survival of some patients. This study was designed to see if sufficient CD34 (+) cells can be harvested at presentation in newly diagnosed patients to administer myeloablative HDM (200 mg/m(2); HDM200) with autograft as primary therapy. This may improve outcome by rapid achievement of complete remission (CR) and possible avoidance of late myelodysplasia as a consequence of non-transplant induction chemotherapy. Thirty untreated patients received 1 g/m(2) methylprednisolone daily (days 1-6) and 12-16 micro g/kg G-CSF daily (days 3-6), and underwent leukapheresis on days 6 and 7. The median CD34(+) cell yield was 1.31 x10(6)/kg (range, 0.23-5.63), and was > or =1 x10(6)/kg in 73%. Cell yields were significantly lower than in 82 historical controls apheresed after completion of induction chemotherapy (median 2.16 x 10(6)/kg), and improved in patients who were apheresed again after induction chemotherapy. Three patients received primary therapy with HDM200 and autograft using these cells and attained CR. We conclude that it is possible to harvest stem cells in three-quarters of untreated myeloma patients. Increasing the number of apheresis procedures is needed to improve the number of CD34(+) cells collected.     

Performance of Crossbred Heifers Supplemented with Linseed Oil,Either Alone or in Combination with Myristic Acid

In order to assess the impact of supplementing linseed oil (LO) and myristic acid (MA) on intake, digestibility and growth, fifteen Karan-Fries heifers (6–12 months of age and 120.15 ± 17.5 kg average body weight) were assigned randomly into three groups of five animals each. Group T1 served as control, fed with hand-mixed basal total mixed ration (TMR) containing concentrate mixture, wheat straw and green berseem (Trifolium alexandrinum) in proportion of 40, 40 and 20 %, respectively. In addition to basal TMR, animals in group T2 were supplemented with 2 % LO and group T3 with 1 % LO + 1 % MA for 120 days. Results revealed that, supplementation of fat sources in both the treatment groups (T2 and T3) did not exhibit any effect on intake of dry matter and crude protein in comparison with group T1. Digestibility coefficients of nutrients did not differ due to treatments, except that of EE, which was greater (P < 0.05) in groups T2 and T3 as compared with control. Furthermore, average daily gain and feed conversion ratio were not influenced by dietary treatments. Additionally, predicted methane emission was decreased up to 20.3 and 18.3 % in groups T2 and T3, respectively than that of group T1. Based on these findings, it was concluded that supplementing either 2 % LO or 1 % LO + 1 % MA may not be a viable nutritional strategy for achieving faster growth response in tropical crossbred dairy heifers at field level.     

Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease

Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.     

Knowledge,attitude, and practice regarding COVID-19 among COVID-19 patients and their correlation with the outcomes: A cross-sectional study

Objective: To assess the knowledge, attitude, and practice (KAP) regarding COVID-19 among COVID-19 patients and their relation with the outcomes.Methods: This cross-sectional study was carried out among COVID-19 patients (18-year-old or older) consecutively admitted to a dedicated COVID-19 hospital located in northwest Rajasthan, India. Data regarding socio-demographic parameters, KAP, and primary composite outcome (admission to intensive care unit, mechanical ventilation, or in-hospital death) were collected. KAP scores were compared between different demographic variables and primary composite outcomes. Association between different demographic variables, primary composite outcomes, and KAP scores were determined through multivariate linear regression. Besides, the correlation among KAP scores was analyzed. Results: Out of the total 222 patients, most of them (65.76％) had average KAP scores towards COVID-19. The mean scores for knowledge were 7.88, with an overall correct rate of 71.63％; the mean attitude scores were 2.42, with an overall correct rate of 60.50％; the mean practice scores were 5.12, with an overall correct rate of 64.00％. Patients who met the primary composite outcomes had higher knowledge scores, but lower attitude and practice scores. The result showed a significant positive correlation between the level of education, socioeconomic class, and knowledge, attitude, and practice towards COVID-19. Knowledge towards COVID-19 was significantly associated with a positive attitude and good practice. Conclusions: Our findings show that adult COVID-19 patients have average KAP towards COVID-19 among COVID-19 patients. Poor attitude and practice towards COVID-19 are associated with adverse outcomes, so it is suggested to strengthen attitude and practice towards COVID-19 to improve the outcomes.     

The polyphenolic phytoalexin polydatin inhibits amyloid aggregation of recombinant human prion protein

Prion diseases involve misfolded and highly infectious aggregates of prion protein (PrP^Sc) which forms amyloid plaques leading to fatal neurodegeneration. The absence of clinically proven therapeutics makes the discovery of effective remedial interventions a prime concern. Herein, we report novel prion intervention by the polyphenolic phytoalexin, polydatin which binds with moderate affinity to the recombinant protease resistant core of human prion protein, encompassing the sequence 90–231 (rPrP^res) and inhibits its conversion into the highly neurotoxic forms. An extensive evaluation using biophysical techniques revealed that polydatin incubated rPrP^res samples generate off-pathway oligomers having reduced cross-β sheet signature, and relatively smaller in size than the native rPrP^res oligomers. The detailed structural analysis using molecular dynamics simulations elucidated the induction of antagonistic mobilities in the β2–α2 loop, α3 helix and the N-terminal amyloidogenic region of prions. This study puts forward novel prion fibrillogenesis inhibitory potential of polydatin, specifically by stabilizing the N-terminal amyloidogenic region. Collectively our results affirm the importance of polydatin in crippling the prion pathogenesis and may serve as a structural scaffold for designing novel therapeutic agents targeting amyloidogenic transition in prions.

Polydatin is found to be a pharmacologically-significant scaffold that can bind to the rPrP^res repertoire and inhibit its conversion to the highly infectious and neurotoxic PrP^Sc-like form, thus acting like a promising anti-prion drug lead.     

Superficial Temporal Fascia Pedicled V-Y Advancement Flap for Scalp Reconstruction

Repair of scalp defects using local hair bearing scalp is technically challenging. Transposition or rotation of local flaps to close the defect has its own disadvantages. Reconstruction of scalp defect using superficial temporal fascia pedicled V-Y advancement flap using both frontal and parietal branches of superficial temporal artery following the excision of a benign and a malignant pathology is reported here. It is possible to reconstruct the defect with hair bearing scalp in a single stage along with primary closure of the donor site using this technique.