Buccal mucosal graft ureteroplasty: The new normal in ureteric reconstructive surgery - Our initial experience with the laparoscopic and robotic approaches.

INTRODUCTION: Upper ureteric stricture is always a challenging case to treat for any urologist. Due to chronic inflammation and multiple interventions, it becomes a complex entity to treat. Buccal Mucosal Graft (BMG) Ureteroplasty is a reconstructive surgery used to treat upper ureteric stricture but the results and experience with this modality is less explored so far. We present here our study of 16 cases of BMG ureteroplasty and its outcomes done by the laparoscopic and robotic approaches. PATIENTS AND METHODS: We analysed 16 cases of BMG ureteroplasty, which were performed both laparoscopically and robotically. All these cases were long ureteric strictures, not amenable to excision or endoscopic intervention. We performed using an onlay BMG without complete mobilisation of the ureter. The omentum or nearby fat was used as a bed for onlay BMG. RESULTS: All 16 patients underwent onlay ureteroplasty. The reconstructed ureter was wrapped with omentum in nine of the cases, while in seven patients, nearby fat was used. The median stricture length was 5.28 cm, and the median operative time was 143.5 min. The mean operative time was 143.5 min. 15 of 16 (93.75%) cases were successfully clinically and radiologically on follow-up. CONCLUSION: Long-segment upper ureteric strictures are a difficult entity to operate on. BMG ureteroplasty is a safe and effective way of managing such strictures. Robot-assisted ureteroplasty provides the benefits of improved ergonomics, easy manoeuvrability and precision surgery to the patients. Our experience with both laparoscopic and robotic ureteroplasty would encourage urologists all over to use BMG ureteroplasty as an effective long-term procedure for ureteral reconstruction.

Surgical and oncological outcomes of robot-assisted versus laparoscopic radical nephroureterectomy for upper-tract urothelial carcinoma: A single-center comparative analysis.

Introduction: We retrospectively compared surgical and oncological outcomes of robot-assisted (RA) radical nephroureterectomy (RNU) in patients of upper-tract urothelial carcinoma with a cohort of patients who underwent the same procedure using a laparoscopic approach. Methods: Data of 63 consecutive patients who underwent RNU with bladder cuff excision (BCE) from 2011 to 2022 at a single tertiary care institution was retrospectively retrieved from the electronically maintained institutional database. Twenty-six cases underwent RNU with a laparoscopic approach, whereas 37 were done by RA approach. Demographic, clinical, surgical, and pathologic details and survival analyses were reported and compared. The tetrafecta of RNU, which include the performance of a BCE, lymphadenectomy, no positive surgical margin, and no major surgical complication, was also reviewed. Results: The mean age and body mass index of the robotic and laparoscopic groups were 61.5 years versus 62.7 years and 23.8 versus 24.9 kg/m2, respectively (P = 0.710 and 0.309). The Charlson Comorbidity Index and upper-tract tumor site distribution were comparable between the groups. There was no significant difference in the distribution of T stage, N stage, presence of multifocality, or lymphovascular invasion between the two groups. Although the rate of concomitant carcinoma in situ was higher in laparoscopic cohort, 42.8% versus 10.8% in robotic cohort (P = 0.004). The laparoscopic group had higher blood transfusion rates (50 vs. 13.5%, P = 0.002) and longer median hospital stays (7 vs. 4 days, P = 0.000). The median follow-up time was 21.5 versus 27 months in the laparoscopic and robotic groups. The RA group was significantly better in the achievement of the tetrafecta outcomes. The 5-year urinary bladder recurrence-free survival (UB RFS) and elsewhere RFS between the laparoscopic and robotic cohorts were 65% versus 72% and 56% versus 70%, respectively (P = 0.510 and 0.190). The laparoscopic cohort had worse 5-year cancer-specific survival and overall survival (64% vs. 90% and 58% vs. 74%, P = 0.04 and 0.08). Conclusion: The robotic approach to RNU and BCE has significantly lower transfusion rates, lower hospital stays, and significantly better cancer-specific survival rates.

Brucella melitensis: Divergence Among Indian Strains and Genetic Characterization of a Strain Isolated from Cattle.

Brucella melitensis primarily affects sheep, goats and is associated with brucellosis in humans, which is one of the world's most widespread neglected zoonotic disease. The current study attempted the determination of genetic diversity through comparative genome analysis of B. melitensis strains reported from India with other countries. The study also reports the isolation and identification of B. melitensis BMNDDB8664 from a cow with a history of abortion, whole-genome sequencing (WGS), determination of virulence factors, genotyping, and comparative genome analysis. Multilocus sequence typing, Multiple locus variable number of tandem repeats analysis (MLVA), and WGS based phylogeny revealed the predominance of ST-8 and genotypes (116 and II respectively) that clustered to the East Mediterranean lineage. Identification of hitherto unreported genotypes by MLVA also indicated the existence and circulation of West Mediterranean and American lineages in India. Though the AMOS-PCR results suggest the BMNDDB8664 isolate as Brucella abortus, the outcomes from multiplex PCR, ribosomal multilocus sequence typing, and WGS analysis confirmed it as B. melitensis. The analysis revealed the presence of adeF gene (aids conferring resistance to fluoro-quinolone and tetracyclines). The isolate lacked two important T4SS genes virB2 and virB7 genes (roles in infection and rifampicin resistance respectively) and also lacked the Brucella suis mprF gene that aids intracellular survival. Further, BMNDDB8664 lacked some of the genes associated with LPS synthesis (wbkB, wbkC) and transport (wzm, wzt) and hence, is most likely a rough strain. WGS-based phylogenetic analysis revealed close genetic relatedness of this BMNDDB8664 with a sheep isolate and two human isolates. The results prompt systematic, broad-based epidemiological studies on brucella infection at the species level. For effective control of human brucellosis, a concerted One Health approach with studies encircling the identification of aetiology at species, strain level to find their prevalence, spread, and inter-host transmission patterns need to be understood, for better design and implementation of effective control strategies in India and other endemic regions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01081-w.

Respiratory Management of Patients With Neuromuscular Weakness: An American College of Chest Physicians Clinical Practice Guideline and Expert Panel Report.

BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations. STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations. RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement. INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.

2/1 dose schedule of sunitinib is superior than the 4/2 regimen for the first-line therapy of clear cell metastatic renal cell carcinoma - An Indian experience.

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.

Male Genital Injuries in Infants Caused by the Bite of Pet Pups: Case Series and Literature Review.

Injuries to male genitalia of infants due to bite of a pet pup are a rare occurrence. Few dog bite injuries to the genitalia of male infants have been reported, however, similar injuries have not been reported by the bite of pet puppies. Male genital injury in three male infants aged 8, 10, and 11 months, by the bite of pet puppies aged 1-2 months, ranged from avulsion of penile and part of scrotal skin with loss of both testes in case 1, a near circumferential laceration of penile skin at the base of penis with scrotal laceration in case 2, and laceration in mid penile shaft resulting in degloving and complete transaction of distal penile urethra with scrotal laceration in case 3. All these infants were appropriately managed surgically (case 1 and 3) and conservatively (case 2) and were given thorough toileting of wound, antibiotics, prophylaxis for tetanus and rabies. Some of these injuries may require complex surgical procedures to reconstruct the male genitalia. Timely management with aggressive intent and conserving the local tissue is the key to success. We describe a case series of injury to the external genitalia of three male infants by the bite of pet puppies, their possible predisposing factors, treatment, and follow-up. A case report and series like this have not been reported in literature so far to the best of our knowledge.

Detection and genetic characterization indicates circulation of a possible new Theileria species (Theileria sp. Yokoyama) in India.

Bovine tropical theileriosis, a tick-borne disease, causes huge economic loss to the Indian dairy industry. Theileriosis in India is mainly caused by Theileria annulata, although the presence of T. orientalis has also been reported. The present study was undertaken to investigate the deaths of cross-bred Holstein Friesen (CBHF) cows on a farm in the state of Telangana, India. Deceased animals had recently calved and prior to death had developed high fever (107 °F) and anaemia. Infected cows were infested with ticks (Hyalomma species). Theileria piroplasms were noticed in the Giemsa stained blood smears. PCR assays further confirmed the presence of Theileria in the blood samples of the infected cows. Partial Tams1 gene sequences from the infected animals shared 99.87% to 100% identity scores with the sequences of Sri Lankan isolates recently proposed as a novel Theileria species (provisionally designated as Theileria sp. Yokoyama). To the best of our knowledge, this is the first report of the novel species of Theileria from India. Infected animals were effectively treated with buparvaquone and oxytetracycline. The introduction of new animals into the farm without risk assessment was found to be a major cause of the outbreak.

Evaluation of commercial ELISA kits for diagnosis of brucellosis in cattle and buffaloes in different epidemiological scenarios.

Seven ELISA kits were evaluated for the fitness of purpose in diagnosing brucellosis among cattle and buffaloes in the endemic scenarios of India. The sera (675 numbers) for the study were sourced from brucellosis-free as well as infected herds. The diagnostic sensitivity (dsn) and specificity (dsp) of the kits were determined by three approaches: based on the results of the Rose Bengal test, history of the animals (sera from infected or naïve animals), and based on the results obtained from the 'majority of the tests'. The dsn and dsp ranged from 65.10% to 98.66%, and 98.04% to 100% respectively. The results and suitability of the kits for diagnostic application in various epidemiological situations were discussed.

Carrier transport theory for twisted bilayer graphene in the metallic regime.

Understanding the normal-metal state transport in twisted bilayer graphene near magic angle is of fundamental importance as it provides insights into the mechanisms responsible for the observed strongly correlated insulating and superconducting phases. Here we provide a rigorous theory for phonon-dominated transport in twisted bilayer graphene describing its unusual signatures in the resistivity (including the variation with electron density, temperature, and twist angle) showing good quantitative agreement with recent experiments. We contrast this with the alternative Planckian dissipation mechanism that we show is incompatible with available experimental data. An accurate treatment of the electron-phonon scattering requires us to go well beyond the usual treatment, including both intraband and interband processes, considering the finite-temperature dynamical screening of the electron-phonon matrix element, and going beyond the linear Dirac dispersion. In addition to explaining the observations in currently available experimental data, we make concrete predictions that can be tested in ongoing experiments.

Sero-diagnostic efficacy of various ELISA kits for diagnosis of infectious bovine rhinotracheitis (IBR) in cattle and buffaloes in India.

Bovine alphaherpesvirus-1 (BoHV-1), the causative agent of infectious bovine rhinotracheitis (IBR), is an economically important viral pathogen affecting cattle and buffaloes. Serological assays are mostly used for detection of the antibodies, but variation has been detected in the diagnostic performances of the individual assay. In the present study, four commercially available ELISA kits {two indirect ELISA (kits A and B) and two blocking ELISA (kits C and D)} were evaluated for the detection of antibodies against BoHV-1 in Indian cattle and buffaloes (fitness of purpose). The diagnostic sensitivity (dsn) and specificity (dsp) of these kits were determined by three ways; considering virus neutralization test (VNT) as gold standard test, using pre-test information of the samples, and majority of tests. Screening of 200 known negative sera (124 cattle, 76 buffaloes) sourced from IBR free farms revealed gB based ELISA kits are more specific than the indirect ELISA kits. Testing of 125 known positive sera (81 cattle, 44 buffaloes) suggests kit B be most sensitive followed by kit C, A and D. Interestingly, kit D was found to be most sensitive for detection of vaccination-induced BoHV-1 antibodies followed by kit B. Similar trend were also observed in the limit of dilution experiment performed using known infected and vaccinated sera. VNT was found to be the most specific test and its use as the gold standard test revealed all kits to have more than 99 % sensitivity. All the ELISA kits could detect BoHV-1 specific antibodies in the IBR vaccinated calves as early as 11 days post-vaccination. In Kappa statistics, an almost perfect agreement between the ELISA kits was recorded. The overall performance of the kits in serodiagnosis of IBR as determined by the area under curve in ROC analysis was good.

Prevalence of antibodies to Anaplasma in cattle and buffaloes of different organized herds in India.

Bovine anaplasmosis is one of the most important tick borne disease in ruminants causing huge economic loss to the dairy industry. A cross-sectional study was carried out to detect serum antibodies to Anaplasma infection in cattle and buffaloes housed in 14 organized herds located at various climatic zones spreading over 9 different states in India. A total of 911 serum samples, collected from 667 cattle and 244 buffaloes, were subjected to a competitive enzyme linked immune-sorbent assay detecting an epitope of major surface protein 5 (MSP5) of Anaplasma. The overall true prevalence was 48.72% (95% CI 45.13-52.32%). The prevalence rate was higher in cattle (51.58%) than buffaloes (40.89%) and the difference was statistically significant (p < 0.05). Indigenous cattle (59.30%) showed higher seropositivity than crossbreed (57.16%) and exotic cattle breeds (42.28%). Although statistically not significant, female (52.37%) showed higher seropositivity than male (46.43%). Similarly, significant difference in prevalence (p < 0.05) was observed for animals reared in different climatic zones with highest prevalence recorded in arid zone (90.49%) and lowest in semi-arid zone (29.83%). Very wide variation in prevalence (9.95-100%) was recorded between farms. The present study indicates endemicity of Anaplasma in India, similar to other tropical and sub-tropical countries of the world. Endemic instability was recorded in some of the studied farms suggesting possibility of outbreak of new clinical cases resulting in economic loss. Therefore, suitable policies and procedures for prevention and control of Anaplasma infection should be adopted in these farms.

Infectious bovine abortions: observations from an organized dairy herd.

Abortions in dairy animals can be caused by several infectious agents. Identification of the actual causal agent(s) is important for formulating suitable control strategies. A 3-year (2016-2018) longitudinal study was conducted in a dairy farm following an abortion storm in the mid- to late gestations. The investigation focused on the seven major infectious abortifacient in cattle, viz. bovine alphaherpesvirus-1 (BoHV-1), bovine viral diarrhoea virus (BVDV), Neospora caninum, Brucella abortus, Coxiella burnetii, Leptospira Hardjo, and Listeria monocytogenes. High seroprevalence was observed for BVDV (79.4%), Leptospira (70.5%), BoHV-1 (53.5%), and Brucella (45.0%) at the beginning of the investigation (August 2016). The incidence proportion increased for BVDV, Leptospira, and Brucella in the following years of the investigation. A strong association of Brucella seropositivity with history of abortion (OR = 3.27) was recorded. Incidence of BoHV-1 reduced during the period of study coincident with systematic IBR inactivated marker vaccination of the herd. Sixty-four abortion cases were investigated for the identification of causative agent(s) by microbial culture, serological (ELISA), and molecular detection (PCR/ real-time PCR). Antibodies to BVDV, Brucella, BoHV-1, Leptospira, Neospora, and Coxiella were detected in 63, 61, 56, 35, 5, and 6 aborting cattle, respectively. Real-time PCR/PCR of clinical specimens detected DNA of Brucella, BoHV-1, Coxiella, Leptospira, and Listeria in 34, 13, 12, 9, and 4 abortion cases, respectively. BVDV and Neospora were not detected in any specimen samples. Brucella abortus isolated from the farm was determined as ST1 by multi-locus sequence typing (MLST). DNA of multiple agents were detected in 21 of the 64 cases (43.75%). Overall, the data suggests, Brucella was the major causative agent, although multiple causative agents circulated in the farm.

Pitcher pot neourethral modification of ileal orthotopic neobladder achieves satisfactory long-term functional and quality of life outcomes with low clean intermittent self-catheterization rate.

Objective: To describe a decade of our experience with a neo-urethral modification of ileal orthotopic neobladder (pitcher pot ONB). Multiple investigators have reported similar modifications. However, long-term longitudinal functional and quality of life (QOL) outcomes are lacking. Methods: Prospectively maintained hospital registry for 238 ONB patients comprising a mix of open and robotic surgery cohorts from 2007 to 2017, and minimum of 2 years of follow-up was retrospectively queried. QOL was evaluated using Bladder Cancer Index (BCI). Longitudinal trends of QOL domain parameters were analysed. List of perioperative variables that have a biologically plausible association with continence, potency, and post-operative BCI QOL sexual, urinary, and bowel domain scores was drawn. Variables included surgery type, Body Mass Index (BMI), T and N stage, neurovascular bundle (NVB) sparing, age, and related pre-operative BCI QOL domain score. Prognostic associations were analysed using multivariable Cox proportional hazard models and multilevel mixed-effects modeling. Results: The study comprised 80 and 158 patients who underwent open and robotic sandwich technique cohorts, respectively. Open surgery was associated with significantly higher "any" complication (40% vs 27%, P-value .050) and "major" complication rate (15% vs 11%, P-value .048). All patients developed a bladder capacity >400 cc with negligible post-void residual urine, and all but one patient achieved spontaneous voiding by the end of study period (<1% clean intermittent self-catheterization [CISC] rate). By 15 months, QOL for all three domains had recovered to reach a plateau. About 45% of patients achieved potency, and the median time to achieve day and night time continence was 9 and 12 months respectively. Lower age and NVBs spared during surgery were found to be significantly associated with the earlier achievement of potency, day and night time continence, as well as better urinary and sexual summary QOL scores. Conclusions: Pitcher pot neobladder achieves satisfactory long-term functional and QOL outcomes with negligible CISC rate. Results were superior with incremental nerves spared during surgery.

Post cholecystectomy common bile duct dilatation and associated symptomatology.

BACKGROUND: Relationship between postcholecystectomy bile duct dilatation and associated symptomatology is a potential dilemma for treating surgeon for which various studies with variable results have been documented. MATERIALS AND METHODS: This study is a 1 year prospective study conducted at IGMC, Shimla after taking proper consent and ethical approval from institutional ethical committee. Total 50 cases of symptomatic cholelithiasis belonging to either sex admitted in surgical wards of IGMC, Shimla for elective surgery were selected for present study. Cholecystectomy was done in all cases after doing all investigations. RESULTS: Postoperatively within 48 h symptoms were observed in 29 patients. Out of these, flatulence was present in 1, nausea and vomiting in 7 and 8, respectively. Combined flatulence vomiting in 5 and flatulence-reflux-nausea in 1 patient. After 1 month of interval, all patients were symptom free. CONCLUSION: Symptoms which were present in the postoperative patients were unrelated to dilatation of common bile duct. Either these symptoms were the persistent symptoms present before the operation or related to anaesthetic drugs.

Shedding of bovine alphaherpesvirus-1 in bovine extended frozen semen in Indian semen stations: A longitudinal analysis.

Infectious bovine rhinotracheitis (IBR) caused by bovine alphaherpesvirus 1 (BoHV-1) is an economically important disease of cattle and buffaloes. Following acute infection, the virus usually attains latency in the sensory neurons. Stress-induced reactivation of latency can cause the infected animals to intermittently shed the virus in body secretions including semen. A longitudinal analysis was carried out to study BoHV-1 shedding in the semen of IBR seropositive cattle and buffaloes. The study involved data generated from the screening of 119,850 extended frozen semen (EFS) batches, collected from 1,229 IBR seropositive bulls, over a period of four years (April 2015 to March 2019). A TaqMan based real-time PCR assay was employed to detect the gB gene BoHV-1 DNA in the EFS batch samples. Each sample was tested in duplicate and amplification in any of the replicates at or below the threshold cycle (Ct ≤ 40) was considered positive. The overall positivity of BoHV-1 in EFS batches was 1.18%. About 41% of the bulls (509 of 1,229) were found to have excreted the virus in semen at least once during the study period. The frequency of viral shedding in buffaloes (0.96%) was significantly lower than that of cattle (1.3%) (p < 0.001). No significant difference was noted in the rate of shedding between the first and the second ejaculates collected on the same day (p = 0.607). The rate of shedding also did not vary among various breeds of cattle (p = 0.454) or with the age of the bulls (p = 0.054). No significant variation in the shedding rate was observed in cattle across different seasons (p = 0.101); while in buffaloes, the rate was higher in autumn (1.2%) than in winter (0.7%) (p = 0.037). The difference in positivity among semen stations was statistically significant (p < 0.001). Analysis of data revealed that ≥100 EFS batch samples/bull were screened from 361 of the 1,229 bulls included in the study. None of the EFS batches screened from 39 of these 361 bulls were found positive during the four years, suggesting they were non-shedders. Further research is warranted to delineate the underlying features of the seropositive non-shedders; following which an adequate risk assessment may be made for the maintenance of infected but non-shedding bulls in semen production.

Adjuvant radiation compares favorably to chemotherapy in patients with carcinoma penis and nodal positivity restricted to groin.

OBJECTIVES: To compare overall survival (OS) between adjuvant radiation, chemotherapy and chemoradiation (CCRT) postsurgery for node-positive patients with carcinoma penis. METHODS: Prospectively maintained registry for 45 patients receiving adjuvant treatment following lymph node dissection from 2011 to 2017, having minimum 6 months follow-up and more than 2 positive inguinal nodes was analyzed. Patients without pelvic nodal positivity (n= 32) were treated by radiotherapy (RT) (n = 25) or chemotherapy (n = 7); CCRT (n = 6) or chemotherapy (n = 7) was used in patients with positive pelvic nodes (n = 13). Data was collected for age, comorbidities, body mass index, tobacco exposure, treatment modality, tumor grade, pathological T and N stage, and extra-nodal extension. OS was compared between different treatment modalities stratifying patients with and without pelvic nodal positivity. Multivariate cox proportional hazard analysis was used to narrow down remaining variables and Inverse Probability Treatment Weights modeling was used to determine average treatment effect. RESULTS: About 12 of 14 patients in the chemotherapy group received both cisplatin and paclitaxel. Pathological T stage, N stage and extra-nodal extension had significant association with OS on multivariate analysis. Among patients with nodal positivity restricted to groin the estimated average OS when all patients received adjuvant RT was 1,438 days (95% confidence interval [CI] 1,256-1,619 days, Pvalue <0.0001). The estimated average OS if all patients received chemotherapy was lower by 1,007 days (95% CI 810-1,202 days, P value <0.0001). Among patients with positive pelvic nodes the estimated average OS when all patients received adjuvant CCRT was 467 days (95% CI 368-566 days, P value <0.0001). The estimated average OS difference if all patients received chemotherapy was 17 days (95% CI -144 to 178 days, Pvalue 0.21). CONCLUSION: In patients with nodal positivity limited to groin, adjuvant RT proved superior to chemotherapy. Among patients with pelvic nodal positivity, CCRT offers no significant OS advantage over combination chemotherapy.

Development and laboratory validation of duplex real-time PCR for simultaneous detection of Brucella and bovine alphaherpesvirus from clinical specimens.

A duplex real­time PCR was developed and validated for the simultaneous detection of Brucella and bovine alphaherpesvirus­1 (BoHV­1) from bovine clinical specimens. The bcsp31 gene of Brucella and gB gene of BoHV­1 were used as targets in the assay. The limit of detection for BoHV­1 was 0.03 TCID50 of virus and 10 plasmid copies containing the target gene while for Brucella it was 4.1 × 101 CFUs. Intra­assay and inter­assay values showed high repeatability and reproducibility of the assay. The diagnostic sensitivity (dsn) and diagnostic specificity (dsp) of the duplex assay were determined by screening 443 clinical specimens and comparing the results with the respective individual assays. The dsn and dsp for detection of Brucella were found to be 95.24% and 95.65%, respectively whereas for BoHV­1, the dsn (100%) and dsp (99.47%) were slightly higher. The duplex assay had a very good degree of agreement with the respective individual real­time PCR test {kappa value 0.97 for Brucella and 0.95 for BoHV­1}. The results of the current study suggest that the duplex assay would be a cost­effective and time­saving alternative for the individual real­time PCR assay for the detection of Brucella and BoHV­1.

TECPR2 mutation-associated respiratory dysregulation: more than central apnea.

None: Children with rare genetic diseases that cause respiratory dysregulation are at particularly high mortality risk due to development of respiratory failure. The tectonin ß-propeller-containing protein 2 (TECPR2) mutations are proposed to cause autophagy defect affecting axonal integrity and development of progressive neurodegenerative and neuromuscular disease. Published TECPR2 mutation cases have described a high prevalence of respiratory failure. We review respiratory pathology in previously published cases and a new case of a 5-year-old girl with previously undescribed TECPR2 mutation demonstrating progressive central apnea due to respiratory cycle dysregulation. This is the first TECPR2 mutation case to demonstrate an ataxic (Biot's) breathing pattern with consistently inconsistent inspiratory and expiratory times and with relatively intact chemoreception during sleep. Therefore, we propose that the central apnea index alone may not be the appropriate marker for mortality risk. Rather, the morbidity and mortality associated with TECPR2 mutations are multisystem in nature and this burden complicates the ultimate needs for ventilation support and prognosis.