Background High dose chemotherapy with autologous hematopoietic cell transplant (auto-HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto-HCT for relapsed patients, particularly in the era of novel therapeutics, is not well-defined. Methods We performed a retrospective analysis of all 44 myeloma patients (24 males, 20 females) who received a second auto-HCT as salvage between 1/3/1992 and 11/4/2008 at M.D. Anderson Cancer Center. Results Median interval between the first and salvage auto HCT was 30 months (range 2–78). Median age at salvage HCT was 54 years (38–73) and median number of salvage treatment regimens was 2 (range 0–5). Eleven (25%) patients had high-risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto. Ten patients (23%) experienced grade 3 or higher non-hematologic toxicity after the salvage auto-HCT. One patient died within 100 days for a treatment-related mortality of 2%. Best responses after salvage chemotherapy + salvage auto-HCT were as follows: CR+ near CR 11%, PR 79%, with an overall response rate of 90%. Eighteen (41%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 41 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) from time of salvage auto-HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression (TTP) after first auto HCT, greater number of prior therapies, African-American race, and IgG subtype were significantly associated with worse OS. Conclusions In selected myeloma patients, a second auto-HCT for salvage therapy is well tolerated with acceptable toxicity. The ORR and PFS are comparable to other salvage regimens.

BACKGROUND: Diverticulitis is separated into complicated and uncomplicated, based on the patient’s presentation at the time of his or her initial attack of acute diverticulitis. OBJECTIVE: The aim of this study was to identify risk factors for persistent complex diverticulitis, defined as an abscess, fistula, or stricture, at the time of elective surgery, and to characterize outcomes in this patient population. DESIGN: This was a retrospective review of 2010 to 2016 in the American College of Surgeons National Surgical Quality Improvement Project database. SETTINGS: Individuals diagnosed with diverticulitis who underwent elective surgery were included. PATIENTS: A total of 1502 patients underwent elective surgery for diverticulitis, of which 559 (37%) patients had a surgical indication of persistent complex diverticulitis. INTERVENTIONS: We performed logistic regression analysis to identify risk factors for complex diverticulitis and evaluated a new prediction model. MAIN OUTCOME MEASURES: The predictive factors of persistent complex diverticulitis for elective colon resection were measured. RESULTS: The patients with complex diverticulitis were older (p < 0.001), had worse functional status (p < 0.001), more comorbidities (diabetes mellitus and hypertension), and a higher Charlson Comorbidity Index (2.7 vs 1.6, p < 0.001). They were more likely to have a history of tobacco or alcohol use (p < 0.001) and to be malnourished. Interestingly, patients found to have persistent complex diverticulitis did not have more episodes than patients with uncomplicated cases did (p = 0.67). Surgical time was longer in complex diverticulitis, and the patients were more likely to require diverting stomas and concurrent resections of adjacent structures. The area under the curve from the test set was (0.75; 95% CI, 0.72–0.78), sensitivity and specificity were 0.890 (95% CI, 0.870–0.891) and 0.450 (95% CI, 0.410–0.490). LIMITATIONS: The study was limited by its retrospective review and observational bias. CONCLUSIONS: Patients undergoing elective surgery for complex diverticulitis did not have more episodes. Instead, complex diverticulitis may be a reflection of a complicated patient, suggesting that complicated patients should have a different algorithm of care at the time of their initial presentation with diverticulitis to prevent the development of complex disease. See Video Abstract at http://links.lww.com/DCR/B183. ¿PODEMOS PREDECIR DIVERTICULITIS QUIRÚRGICAMENTE COMPLEJA EN CASOS ELECTIVOS? ANTECEDENTES: La diverticulitis se divide en complicada y sin complicaciones, según la presentación del paciente en el momento de su ataque inicial de diverticulitis aguda. OBJETIVO: El objetivo de este estudio fue identificar los factores de riesgo para la diverticulitis compleja persistente, definida como un absceso, fístula o estenosis, en el momento de la cirugía electiva, y caracterizar los resultados en esta población de pacientes. DISEÑO: Esta fue una revisión retrospectiva del 2010–2016 en la base de datos del Proyecto de Mejora de la Calidad Quirúrgica Nacional del Colegio Estadounidense de Cirujanos. AJUSTES: Se incluyeron individuos diagnosticados con diverticulitis que se sometieron a cirugía electiva. PACIENTES: 1502 pacientes fueron sometidos a cirugía electiva por diverticulitis, de los cuales 559 (37%) pacientes tenían una indicación quirúrgica de diverticulitis compleja persistente. INTERVENCIONES: Realizamos un análisis de regresión logística para identificar los factores de riesgo de diverticulitis compleja y evaluamos un nuevo modelo de predicción. RESULTADOS DE MEDIDAS PRINCIPALES: Se midieron los factores predictivos de diverticulitis compleja persistente para la resección de colon electiva. RESULTADOS: Los pacientes con diverticulitis compleja eran mayores (p <0,001), tenían un peor estado funcional (p <0,001), más comorbilidades (diabetes e hipertensión) y un índice de comorbilidad de Charlson más alto (2,7 frente a 1,6, p <0,001). Tenían más probabilidades de tener antecedentes de consumo de tabaco o alcohol (p <0.001) y estar desnutridos. Curiosamente, los pacientes con diverticulitis compleja persistente no tuvieron más episodios que los pacientes sin complicaciones (p = 0,67). El tiempo quirúrgico fue más largo en la diverticulitis compleja y era más probable que requirieran estomas para desvio y resecciones concurrentes de estructuras adyacentes. El área bajo la curva de prueba fue (0.75, intervalo de confianza del 95% 0.72-0.78), la sensibilidad y la especificidad fueron 0.890 (intervalo de confianza del 95%; 0.870-0.891) y 0.450 (intervalo de confianza del 95%; 0.410-0.490), respectivamente. LIMITACIONES: El estudio estuvo limitado por su revisión retrospectiva y sesgo observacional. CONCLUSIONES: Los pacientes sometidos a cirugía electiva por diverticulitis compleja no tuvieron más episodios. En cambio, la diverticulitis compleja puede ser un reflejo de un paciente complicado, lo que sugiere que los pacientes complicados deben tener un algoritmo de atención diferente al momento de su presentación inicial con diverticulitis para prevenir el desarrollo de una enfermedad compleja. Consulte Video Resumen en http://links.lww.com/DCR/B183. (Traducción—Dr. Yesenia Rojas-Kahlil)

Background Transanal TME (TaTME) was introduced to improve access to the pelvis in difficult cases (male sex, obesity and mid to low rectal cancers) and reduce the risk of anastomotic leak by avoiding cross stapling. In April 2018 the Norwegian hospital to whom all local; recurrences for rectal cancer are referred reported an unexpected rise in early multifocal local recurrences of 9.5% following TaTME compared with 3.4% following conventional TME leading to a nationwide moratorium on the procedure and ending, in an editorial published on the British Journal of Surgery in August 2020, by saying that other countries should consider the issue in the context of local practices and results. There are limited data concerning oncological outcomes of TaTME compared to conventional TME. The aim of this study was to report perioperative and oncological outcomes for patients with rectal cancer treated with TaTME in a high-volume, experienced UK centre. Methods From January 2015 to January 2020 consecutive patients with histologically confirmed rectal cancer having TaTME at Worcestershire Royal Hospital NHS were prospectively entered into an online international registry. Patients were followed according to local protocol with clinical examination, tumour markers, endoscopy and radiology. Results Seventy patients underwent TaTME for rectal cancer. The median distance of the tumour from the anorectal junction was 4 cm (IQR 2-5). The mesorectal margin was involved in 20 (1%) patients, all of whom received neoadjuvant chemoradiotherapy. Overall survival was 94% at a median follow-up of 15 months (IQR 9-31 months). Distant recurrence occurred in 12 (17%) of patients at a median of 14 months (IQR 10-17 months). The 18-month stoma-free survival rate was 66%. Conclusions A local recurrence rate of 5.7% supports the oncological safety of TaTME for rectal cancer.

Aims The primary aim of this paper was to outline the processes involved in building the Partners Arthroplasty Registry (PAR), established in April 2016 to capture baseline and outcome data for patients undergoing arthroplasty in a regional healthcare system. A secondary aim was to determine the quality of PAR’s data. A tertiary aim was to report preliminary findings from the registry and contributions to quality improvement initiatives and research up to March 2019. Methods Structured Query Language was used to obtain data relating to patients who underwent total hip or knee arthroplasty (THA and TKA) from the hospital network’s electronic medical record (EMR) system to be included in the PAR. Data were stored in a secure database and visualized in dashboards. Quality assurance of PAR data was performed by review of the medical records. Capture rate was determined by comparing two months of PAR data with operating room schedules. Linear and binary logistic regression models were constructed to determine if length of stay (LOS), discharge to a care home, and readmission rates improved between 2016 and 2019. Results The PAR captured 16,163 THAs and TKAs between April 2016 and March 2019, performed in seven hospitals by 110 surgeons. Manual comparison to operating schedules showed a 100% capture rate. Review of the records was performed for 2,603 random operations; 2,298 (88.3%) had complete and accurate data. The PAR provided the data for three abstracts presented at international conferences and has led to preoperative mental health treatment as a quality improvement initiative in the participating institutions. For primary THA and TKA surgeries, the LOS decreased significantly (p < 0.001) and the rate of home discharge increased significantly (p < 0.001) between 2016 and 2019. Readmission rates did not correlated with the date of surgery (p = 0.953). Conclusion The PAR has high rates of coverage (the number of patients treated within the Partners healthcare network) and data completion and can be used for both research purposes and quality improvement. The same method of creating a registry that was used in the PAR can be applied to hospitals using similar EMR systems. Cite this article: Bone Joint J 2020;102-B(7 Supple B):90–98.

The hormone melatonin regulates the biological clock and assist in various other physiologies of vertebrates. Present work is intended to check the affinity of saccharin towards the melatonin receptors and the possible role of saccharin interference in the melatonin physiology. The present in vitro study is based on the working model of isolated scale melanophores in the dorso-lateral region of Labeo rohita. The pigment cells were incubated in the agonist and the antagonists within a limited time frame and subsequently their Melanophore Size Index (MSI) were calculated. The inferences were drafted through the observed signal transduction upshots in pigment translocations within the melanophores. Saccharin, in a wide dose range, has consistently induced a concentration-related aggregation similar to the aggregatory effect as shown by melatonin on the melanophores. Binding of saccharin with the receptors and eliciting its aggregatory effect is partially dependent on the release of neurotransmitters. The aggregatory effects were found to be significantly blocked by luzindole, K185, and prazosin, which are the potent melatonin receptor blockers, at the higher concentrations of saccharin. Hence, all the three subtypes of melatonin receptors viz. MT₁, MT₂, and MT₃ are participating in saccharin-mediated aggregations. Blocking by neomycin shows that Ca²⁺ ions are very crucial in dispensing the aggregatory effect of the sweetener. This research demands that an intensive and careful thorough study should be made about saccharin, specifically its effects upon melatonin physiology, before its unwarranted use as the food ingredients for human use.

Effects of three prostaglandins (i.e., prostanoids) and one of its precursors, arachidonic acid, were examined on the melanophores of the fish Labeo rohita (Ham.). PGE₁, PGE₂, PGF(2α) and arachidonic acid elicit a concentration-related dispersion in the fish melanophores. In vitro analysis of melanophores was performed through incubation of the isolated fish scales in different agonists and antagonists solutions. Dispersal effect of prostanoids may be mediated directly through the typical receptors or indirectly through release of neurotransmitter substance(s) from the melanophore nerve endings. Denervation of fish melanophores rendered them insensitive to prostanoid (PGF(2α)). Propranolol and verapamil completely inhibited the dispersal effects of PGF(2α); theophylline and indomethacine blocked the effects of higher concentrations of PGF(2α). During dispersing influence of PGF(2α), a free flux of Ca²⁺ ions was required and the indirectly released substance(s) from melanophore nerve endings would be the catecholamines of adrenergic and purinergic in nature.

Whole genome pooled sequence data of 12 Pakistani Teddy goats is analyzed for positive selection signatures as their breed defining characteristics. Selection imprints left in the Teddy genome are unveiled by genomic differentiation after the successful paired-end alignment of 635,357,043 reads with (ARS1) reference genome assembly. Pooled-heterozygosity ( ) and Tajima&rsquo;s D (TD) are applied for validation and getting better hits of selection signals, while pairwise FST statistics is conducted on Teddy vs. Bezoar (wild goat ancestor) for genomic differentiation. Annotation of regions under positive selection reveals 59 genes underlying production and adaptive traits. score &ge; 5 detected six windows having highest scores on Chr. 29, 9, 25, 15 and 14 that harbor HRASLS5, LACE1 and AXIN1 genes which are candidate for embryonic development, lactation and body height. Secondly, TD value of &le; -2.2 showed 4 windows with very strong hits on Chr.5 &amp; 9 harbor STIM1 and ADM genes related to body mass and weight. Lastly, FST analysis generated three strong signals with threshold &le; 0.42 on Chr.12 &amp; 5 harbor ITGB1 gene associated with milk production &amp; lactation traits. Other significant selection signatures encompass genes associated with wool production, prolificacy, immunity and coat colors. In brief, this study identified the genes under selection in this Pakistani goat breed that will be helpful to refining future breeding policies and converging required productive traits within and across other goat breeds and to explore full genetic potential of this valued livestock species.

No abstract