Minimally invasive techniques as a first line approach in the management of emphysematous pyelonephritis - A single centre experience.

Context: Emphysematous pyelonephritis (EPN) is a dangerous necrotizing infection of the kidney involving the diabetics with a high case fatality rate. Recent medical literature has shown shifting of treatment strategy from conventional radical approach to minimally invasive approach. Aims: The aim of our study was to assess the role of minimally invasive stepwise decompression techniques in the management of EPN and preservation of the renal unit. Settings and Design: : This was a retrospective observational study conducted from June 2017 to April 2020 at a tertiary care centre. Material and Methods: We reviewed the hospital online records of 18 patients diagnosed with EPN for patient demographics, clinical profiles, co-morbidities, laboratory and, radiological investigations, surgical interventions performed and the outcomes. The severity of EPN was graded as per the Huang classification. Patients underwent surgical interventions as per the treatment protocol and response was assessed. Statistical Analysis Used: Descriptive statistics was applied. Results: Diabetes mellitus was present in 15 (83.3%) patients along with urinary tract obstruction in 8 (44.4%) patients. Flank pain (77.7%) was the most common presenting clinical feature while Escherichia coli (55.5%) were the most common causative organism. Most patients (50%) had Type- II EPN, all of which were managed successfully by minimally invasive procedures. In total seventeen patients (94.4%) responded well while one patient (5.5%) underwent nephrectomy with no mortality. Conclusions: Renal salvage in EPN requires multidisciplinary approach including the initial medical management followed by properly selected stepwise decompressive surgical techniques. Conservative management and decompression techniques have shown to improve patient's outcome, reducing the traditional morbidity associated with nephrectomy.

iTRAQ reveals candidate pancreatic cancer serum biomarkers: influence of obstructive jaundice on their performance.

BACKGROUND: The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance. METHODS: Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects. RESULTS: Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-ß glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects. CONCLUSIONS: The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.

Current status of GV1001 and other telomerase vaccination strategies in the treatment of cancer.

GV1001 is a telomerase-specific, promiscuous class II peptide vaccine which is currently in an advanced stage of clinical development. This article reviews the biological rationale underpinning the design of ongoing studies with the vaccine as well as its immunogenicity and clinical activity. It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.

Deciphering antihormone-induced compensatory mechanisms in breast cancer and their therapeutic implications.

Breast cancer inhibition by antihormones is rarely complete, and our studies using responsive models reveal the remarkable flexibility of breast cancer cells in recruiting alternative signalling to limit maximal anti-tumour effects of oestrogen receptor alpha (ER) blockade. The recruited mechanism involves antihormone-induced expression of oestrogen-repressed signalling genes. For example, epidermal growth factor receptor gene (EGFR) is induced by antioestrogens and maintains residual kinase and ER phosphorylation, cell survival genes, and thereby allows incomplete antihormone response and emergence of resistance. Microarrays are revealing the breadth of antihormone-induced genes that may attenuate growth inhibition, including NFkappaB, Bag1, 14-3-3zeta and tyrosine kinases, such as HER2 and Lyn. Three concepts are emerging: first, some genes are induced exclusively by antioestrogens, while others extend to oestrogen deprivation; secondly, some are transiently induced, while others persist into resistance; finally, some confer additional adverse features when tumour cells are in an appropriate context. Among the latter is CD59 whose antioestrogen induction may permit evasion of immune surveillance in vivo. Also, induction of pro-invasive genes (including NFkappaB, RhoE and delta-catenin) may underlie our findings that antioestrogens can markedly stimulate migratory behaviour when tumour intercellular contacts are compromised. Based on our promising studies selectively inhibiting EGFR (gefitinib), NFkappaB (parthenolide) or CD59 (neutralising antibody) together with antioestrogens, we propose that co-targeting strategies could markedly improve anti-tumour activity (notably enhancing cell kill) during the antihormone-responsive phase. Furthermore, subverting those induced signalling genes that are retained into resistance (e.g. EGFR, NFkappaB, HER2) may prove valuable in this state. Alongside future deciphering and targeting of genes underlying antioestrogen-promoted invasiveness, embracing of intelligent combination strategies could significantly extend patient survival.

The role of blinded interviews in the assessment of surgical residency candidates.

BACKGROUND: Interview assessments of surgical residency candidates may be biased by prior knowledge of objective data. METHODS: Each candidate (site 1: n = 88; site 2: n = 44) underwent two interviews, one by faculty members informed only of a candidate's medical school, the second with prior knowledge of the complete application. Interviewers (site 1: n = 28; site 2: n = 14) independently rated candidates overall and on nine qualitative characteristics. RESULTS: At site 1 only, overall ratings were significantly more favorable for unblinded than blinded interviews (23.0 +/- 17.7 versus 32.6 +/- 23.1, P < 0.01). Blinded and unblinded overall ratings correlated -0.01 (P = 0.90) and 0.31 (P = 0.05) at sites 1 and 2, respectively. At site 1 only, overall ratings correlated significantly with USMLE scores, but in opposite directions for blinded (r = 0.32, P = 0.003) versus unblinded interviews (r = -0.32, P = 0.003). CONCLUSION: Interview assessments may be influenced by objective data, and faculty and program variables. The value of blinded interviewing may vary as a function of individual program characteristics.

Understanding lesbians' mammography utilization.

Lesbians face unique barriers to health care, and may be at higher risk for breast cancer than are other women. Yet, no research on lesbians and mammography utilization exists. We conducted telephone interviews of 107 lesbians aged 51-80, of whom 68 had had mammograms in the last year and 39 had not. Responses to open-ended questions identified the barriers lesbians face in obtaining mammography, lesbians, reasons for obtaining mammograms, and factors that would help lesbians obtain mammograms. Some issues identified were particular to lesbians; many issues were common to those identified by general samples of women (which include lesbians).

Treatment of advanced Kaposi's sarcoma using a combination of bleomycin and vincristine.

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.

Dietary practices and pregnancy discomforts among urban blacks.

In this prospective study, we investigated the relationship between dietary practices and pregnancy discomforts among 50 urban black American women during their first and third trimesters of pregnancy. Subjects were interviewed during their regular prenatal clinic visits for information about their previous 24-hour dietary intake, the presence and severity of pregnancy discomforts occurring in the previous month, and pertinent demographic data. Findings indicated that high intake of meat products but low or no intake of vegetables was correlated with nausea, little or no intake of milk products was correlated with heartburn, and low or no intake of citrus fruit but intake of vitamin and iron supplements was correlated with heartburn, constipation, and sleeping difficulty. Replication of the study with a larger sample is warranted so as to provide further validity to the findings.

Experimental hematogenous endophthalmitis caused by Candida albicans.

For a rabbit model of hematogenous endophthalmitis caused by Candida, 80 New Zealand white rabbits were given intravenous injections of 10-5 Candida albicans. Two weeks after infection 88 percent of infected rabbits had ocular lesions with clinical appearance identical to that of human lesions. Cultures of the chorioretina and kidneys averaged 10-4.3 and 10-3.9 organisms per g of tissue, respectively, three days after infection and remained positive for 38 days. Ninety-five percent of rabbits with positive cultures of the chorioretina had positive cultures from other organs. The ocular lesions were focal chorioretinitis characterized by a combination of granulomatous and acute suppurative reactions. Hematogenous endophthalmitis caused by Candida in the rabbit is a useful model for study of the pathogenesis and treatment of the disease in humans.