Lesions of the rotator cuff (RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an age-dependent increase in numbers. Other associated factors include a history of trauma, limb dominance, contralateral shoulder, smoking-status, hypercholesterolemia, posture and occupational dispositions. The challenge lies in early diagnosis since a high proportion of patients are asymptomatic. Pain and decreasing shoulder power and function should alert the heedful practitioner in recognizing promptly the onset or aggravation of existing RC tears. Partial-thickness tears (PTT) can be bursal-sided or articular-sided tears. Over the course of time, PTT enlarge and propagate into full-thickness tears (FTT) and develop distinct chronic pathological changes due to muscle retraction, fatty infiltration and muscle atrophy. These lead to a reduction in tendon elasticity and viability. Eventually, the glenohumeral joint experiences a series of degenerative alterations - cuff tear arthropathy. To avert this, a vigilant clinician must utilize and corroborate clinical skill and radiological findings to identify tear progression. Modern radio-diagnostic means of ultrasonography and magnetic resonance imaging provide excellent visualization of structural details and are crucial in determining further course of action for these patients. Physical therapy along with activity modifications, anti-inflammatory and analgesic medications form the pillars of nonoperative treatment. Elderly patients with minimal functional demands can be managed conservatively and reassessed at frequent intervals. Regular monitoring helps in isolating patients who require surgical interventions. Early surgery should be considered in younger, active and symptomatic, healthy patients. In addition to being cost-effective, this helps in providing a functional shoulder with a stable cuff. An easily reproducible technique of maximal strength and sturdiness should by chosen among the armamentarium of the shoulder surgeon. Grade 1 PTTs do well with debridement while more severe lesions mandate repair either by trans-tendon technique or repair following conversion into FTT. Early repair of repairable FTT can avoid appearance and progression of disability and weakness. The choice of surgery varies from surgeon-to-surgeon with arthroscopy taking the lead in the current scenario. The double-row repairs have an edge over the single-row technique in some patients especially those with massive tears. Stronger, cost-effective and improved functional scores can be obtained by the former. Both early and delayed postoperative rehabilitation programmes have led to comparable outcomes. Guarded results may be anticipated in patients in extremes of age, presence of comorbidities and severe tear patters. Overall, satisfactory results are obtained with timely diagnosis and execution of the appropriate treatment modality.
Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities.
Smartphones have emerged as essential tools providing assistance in patient care, monitoring, rehabilitation, communication, diagnosis, teaching, research and reference. Among innumerable communication apps, WhatsApp has been widely popular and cost effective. The aim of our study was to report the impact of introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool on (1) awareness of patient-related information, (2) efficiency of the handover process and (3) duration of traditional morning handovers among orthopedic residents in a 300-bedded tertiary care teaching center. Written handovers and paging used for communication at our center led to occasional inefficiencies among residents. Widespread use, low cost, availability and double password protection (phone lock and WhatsApp lock) made WhatsApp's group conversation feature an ideal tool for intradepartmental patient-related communication. Twenty-five consecutive admissions before and after WhatsApp (BW, AW) were included in the study. Eight orthopedic residents attempted fifty randomly arranged questions based on the twenty-five patients in each study period. A null hypothesis that introduction of WhatsApp group would neither increase the awareness of patient-related information nor improve the efficiency of the handovers among residents was assumed. A significant improvement observed in scores obtained by residents in the AW group led to rejection of the null hypothesis. The residents also reported swifter and efficient handovers after the introduction of WhatsApp. Our results indicate that the introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool can bring about an improvement in patient-related awareness, communication and handovers among orthopedic residents.
Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies.
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