Predictors of clinical outcomes after non-operative management of symptomatic full-thickness rotator cuff tears

BACKGROUNDPrevious studies have shown that non-surgical management can be an effective treatment strategy for many patients with rotator cuff tears. Despite the prevalence of rotator cuff disease, few studies have examined the patient and tear related factors that predict outcomes of nonsurgical management in this cohort of patients.AIMTo identify factors that are associated with changes in patient reported outcomes over time in individuals with full-thickness rotator cuff tears treated without surgery. METHODSA cohort of 59 patients who underwent non-surgical management of full thickness rotator cuff tears with a minimum of 1-year follow-up were identified from our institutional registry. Patient demographics, comorbidities and tear characteristics were collected at initial presentation. Outcome measures were collected at baseline and at each clinical follow-up, which included Western Ontario Rotator Cuff (WORC) index, American Shoulder and Elbow Surgeons score, Visual Analog Scale for pain and Single Assessment Numerical Evaluation. Multi- and univariate regression analyses were used to determine the impact of each patient and tear related variable on final WORC scores and change in WORC scores throughout the study. RESULTSIn this non-surgical cohort, all patient-reported outcome measures significantly improved compared to baseline at 1 and 2-year follow-up. There was no significant difference in outcomes between 1 and 2 years. The average improvement surpassed the published minimal clinically important differences values for WORC, American Shoulder and Elbow Surgeons, Visual Analog Scale pain and Single Assessment Numerical Evaluation scores. Regression analysis identified female gender (β = - 19.88, P = 0.003), smoking (β = -29.98, P = 0.014) and significant subscapularis fatty infiltration (β = -15.35, P = 0.024) as predictors of less favorable WORC scores at 1 year, and female gender (β = -19.09, P = 0.015) alone as a predictor of lower WORC scores at 2 years. Patients with symptom duration greater than 1 year at presentation reported less improvement in WORC scores at 1-year follow-up (β = -14.63, P = 0.052) and patients with traumatic tears reported greater improvements in WORC scores at 2-year follow-up (β = 17.37, P = 0.031). CONCLUSIONPatients with full thickness rotator cuff tears can achieve and maintain clinically meaningful benefit from non-surgical management through 2-year follow-up. Female patients, smokers, and those with significant subscapularis fatty infiltration tend to have lower overall WORC scores at 1-year follow-up, and females also have lower WORC scores at 2-year follow-up. Patients presenting with symptoms greater than 1 year had less clinical improvement at 1-year follow-up, and those with traumatic tears had greater clinical improvement at 2-year follow-up.     

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study

ObjectivesTo develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases.Materials and methodsA review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer.ResultsLimited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic.ConclusionsThe international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.     

Transjugular intrahepatic portosystemic shunt for refractory ascites: an analysis of the literature on efficacy, morbidity, and mortality

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is frequently used to treat patients with refractory ascites, but its role is controversial. We sought to determine from the literature the efficacy, morbidity, and mortality associated with TIPS for refractory ascites. METHODS: We searched MEDLINE and identified studies published in English from January, 1985, to March, 2003, that evaluated the effect of TIPS in patients with refractory ascites. Outcomes that were analyzed included complete resolution of ascites, reduction in ascites, mortality, encephalopathy, stenosis, and renal function. Data were analyzed on an intention to treat basis. RESULTS: Of 25 studies identified, 16 were included in the analysis. The pooled estimate for complete response at 6 months was 45% and for any response (complete and partial) was 63%. Pooled 6-month mortality after TIPS was 36%. Risk factors for mortality included renal insufficiency (serum creatinine >1.5 mg/dl), hyperbilirubinemia (total bilirubin >3 mg/dl), advanced age (>60 yr), and poor response to TIPS. The pooled rate of new or worsening encephalopathy after TIPS was 32%. In most cases, encephalopathy was managed medically or by reduction in shunt size; however, refractory cases were associated with 100% mortality in most studies. Studies reporting the effect of TIPS on kidney function showed improvement in creatinine clearance and urinary sodium excretion. CONCLUSIONS: TIPS is effective in eliminating ascites or substantially reducing ascites in cases refractory to medical therapy. Renal insufficiency, refractory encephalopathy, and hyperbilirubinemia were consistently associated with mortality after TIPS. In individuals with risk factors for mortality, alternative strategies should be recommended.     

Common Injuries in Professional Football Quarterbacks

Purpose of Review

Professional football quarterbacks are at particular risk for upper extremity injuries due to the physical demands of their position coupled with the inherent risks associated with professional football. This review sought to evaluate current clinical literature to better characterize the injury profile unique to this athletic population.

Recent Findings

Shoulder injuries are the most prevented upper extremity injury among professional football quarterbacks. The quarterback position is disproportionately impacted by shoulder injuries when compared to professional athletes at other positions. Moreover, contrary to other professional throwing athletes, the majority of upper extremity injuries in the professional quarterback result from direct contact as opposed to the throwing motion.

Summary

The injury profile among professional quarterbacks is unique compared to other positions and other overhead professional throwing athletes. Overall, a paucity of high quality clinical evidence exists to support the management of injuries in this elite population.

     

Muscle Fibers are Injured at the Time of Acute and Chronic Rotator Cuff Repair

BackgroundRotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain.Questions/purposesWe hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury?MethodsWe used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey’s post hoc sorting.ResultsChronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers.ConclusionsIn a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint.

Clinical Relevance

In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.     

The Effect of Granulocyte-colony Stimulating Factor on Rotator Cuff Healing After Injury and Repair

Background

The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF).

Questions/purposes

We asked: (1) Does G-CSF administration increase local cellularity after acute rotator cuff repair? (2) Is there histologic evidence that G-CSF improved organization at the healing enthesis? (3) Does G-CSF administration improve biomechanical properties of the healing supraspinatus tendon-bone complex? (4) Are there micro-MRI-based observations indicating G-CSF-augmented tendon-bone healing?

Methods

After creation of full-thickness supraspinatus tendon defects with immediate repair, 52 rats were randomized to control or G-CSF-treated groups. G-CSF was administered for 5 days after repair and rats were euthanized at 12 or 19 postoperative days. Shoulders were subjected to micro-MR imaging, stress relaxation, and load-to-failure as well as blinded histologic and histomorphometric analyses.

Results

G-CSF-treated animals had significantly higher cellularity composite scores at 12 and 19 days compared with both control (12 days: 7.40 ± 1.14 [confidence interval {CI}, 5.98–8.81] versus 4.50 ± 0.57 [CI, 3.58–5.41], p = 0.038; 19 days: 8.00 ± 1.00 [CI, 6.75–9.24] versus 5.40 ± 0.89 [CI, 4.28–6.51], p = 0.023) and normal animals (12 days: p = 0.029; 19 days: p = 0.019). There was no significant difference between G-CSF-treated animals or control animals in ultimate stress (MPa) and strain, modulus (MPa), or yield stress (MPa) and strain at either 12 days (p = 1.000, p = 0.104, p = 1.000, p = 0.909, and p = 0.483, respectively) or 19 days (p = 0.999, p = 0.964, p = 1.000, p = 0.988, and p = 0.904, respectively). There was no difference in MRI score between G-CSF and control animals at either 12 days (2.7 ± 1.8 [CI, 1.08–4.24] versus 2.3 ± 1.8 [CI, 0.49–4.17], p = 0.623) or 19 days (2.5 ± 1.4 [CI, 1.05–3.94] versus 2.3 ± 1.5 [CI, 0.75–3.91], p = 0.737). G-CSF-treated animals exhibited significantly lower relative bone volume compared with normal animals in the entire humeral head (24.89 ± 3.80 [CI, 20.17–29.60) versus 32.50 ± 2.38 [CI, 29.99–35.01], p = 0.009) and at the supraspinatus insertion (25.67 ± 5.33 [CI, 19.04–32.29] versus 33.36 ± 1.69 [CI, 31.58–35.14], p = 0.027) at 12 days. Further analysis did not reveal any additional significant relationships with respect to regional bone volume or trabecular thickness between groups and time points (p > 0.05).

Clinical Relevance

Postoperative stem cell mobilization agents may be an effective way to enhance rotator cuff repair. Future studies regarding the kinetics of mobilization, the homing capacity of mobilized cells to injured tissues, and the ability of homing cells to participate in regenerative pathways are necessary.     

Groups of coevolving positions provide drug resistance to Mycobacterium tuberculosis: A study using targets of first-line antituberculosis drugs

Drug resistance has been associated with point mutations in coding regions leading to an altered protein sequence and structure. Such changes have been seen as isolated events occurring at various positions in a sequence. However, we hypothesise that it is not a single mutation at a specific position but a group of positions that coevolve in a correlated fashion to increase the fitness of a target protein against a drug. To prove the hypothesis, selected protein sequences of Mycobacterium tuberculosis drug resistance genes were successfully screened using a bioinformatics approach to detect groups of coevolving amino acids at important structural and functional positions in the targets of first-line antituberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide). The algorithmically characterised genetic mutations and the lineage-specific single nucleotide polymorphisms (SNPs) detected previously in drug resistance genes of M. tuberculosis complex genomes were also found in the identified coevolving groups. Mapping of coevolving positions to the secondary structure of proteins clearly indicates the preference of amino acid residues in the helix to coevolve. Moreover, active-site residues of some candidate proteins were also found in coevolving groups. The coevolving groups detected in this study will be useful to gain new insights into the molecular and evolutionary basis of drug resistance. This work provides an important first step towards finding solutions to the multidrug resistance problem through coevolution analysis of proteins, in turn helping to develop new drug regimens against pathogens, including M. tuberculosis.