Sex and infection

At the recent meeting of the American Shoulder and Elbow Surgeons, Doctor Dominique Rouleau gave a most informative presentation on the relationship between sex, gender and the risk of infection. She pointed us to this article Sex and Gender Differences in Bacterial Infections, that makes some clinically relevant points:

Biological sex (defined by sex chromosome complement, sex steroid hormones, and reproductive organs) has been shown to influence susceptibility to infection, pathophysiology, immune responses, clinical presentation, disease severity, and response to treatment and vaccination. Women tend to have stronger immune responses to self and foreign antigens than men, resulting in sex-based differences in autoimmunity and infectious diseases. Males are generally more susceptible than females to bacterial infections. 

On the other hand, gender roles (referring to characteristics that are socially constructed) and social norms can influence risk factors and exposure to infection, determine health-seeking behaviors, quality of health care, adherence to treatment recommendations, and can affect therapeutic decisions.

Genetic factors.

Female sex is determined by having two X chromosomes. The additional X enhances the strength and diversity of the female's immune response.

Immune response

Females tend to have stronger innate and adaptive immune responses than males. Females have higher neutrophil counts in peripheral blood and more efficient antigen-presenting cells. Females have greater antibody responses, higher B cell numbers, higher IgM and IgG levels,

Sex Hormones

After puberty, concentrations of estrogens and progesterone in females and androgens in males rise significantly. During this period, there is generally a male bias in infectious diseases, with males being more frequently and more severely affected by bacterial, viral, and parasitic infections, whereas females are more affected by autoimmune disease. Estrogen, progesterone and androgens influence immune responses by binding to specific receptors expressed in immune cells, including lymphocytes, macrophages, and dendritic cells, and can also have a direct effect over bacterial metabolism, growth, and expression of virulence factors.

Gender

Gender-related occupational and recreational activities can affect exposure to pathogens. Women are more likely to assume caretaking roles, making them more exposed to childhood diseases. On the other hand, men wash their hands less often than women. 

Sex and Gender Differences in Bacterial Diseases

Females have higher rates of upper respiratory infections while men more commonly have lower respiratory infections.

Urinary tract infections are more common in females but more severe in males.

Gastointestinal infections are more common in males.

Men have more frequent and more severe sexually transmitted diseases.

Men are more prone to have sepsis than females.

Comment: This article provides an overview of sex and gender differences in pathophysiology, incidence, clinical presentation, disease course, response to treatment, and outcome. It found that biological and gender factors come into play and their recognition is essential to improving patient care. Behavioral differences play an important role in the exposure to pathogens, whereas sex differences in the immune response are directly influenced by sex chromosome complement and concentrations of sex steroid hormones.

While the article did not deal with orthopaedic infections or with the more common bacteria we encounter in our practices - cutibacterium, streptococcus species and staphylococcus species - we can suspect that sex and gender differences are important considerations in our practices. For example, it is recognized that cutibacterium infections are more common in young men and in those with high testosterone serum levels. This knowledge informs our preoperative discussions with patients, our use of prophylaxis, and our suspicion of infection when the clinical outcome is not as expected.

Of note, the only serious Cutibacterium periprosthetic shoulder infection we've encountered was in a woman body builder who used large doses of supplemental testosterone.

Further research will show us how we can understand and manage our patients' risk factors for infection and autoimmune diseases.

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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link). 

Sex and shoulder arthroplasty

 Gender Influences on Shoulder Arthroplasty

These authors reviewed the recent literature regarding the influence of "gender" on shoulder arthroplasty. They found that while both female and male patients generally benefit from shoulder arthroplasty, several differences may existbin preoperative factors, acute perioperative complications, and postoperative outcomes. 

Female patients were found to 

undergo shoulder arthroplasty at an older age,

have greater levels of preoperative disability and 

have different preoperative expectations. 

Perioperatively, female patients may be at increased risk of 

extended length of stay, 

postoperative thromboembolic events, and 

blood transfusion. 

Postoperatively, female patients may achieve 

lower postoperative functional scores and 

decreased range of motion. 

Finally, female patients may be at greater risk for 

periprosthetic fracture and 

aseptic loosening 

while having a lower risk for 

periprosthetic infection and 

revision surgery.

Comment: In considering these findings, it is important to distinguish sex and gender (the term used by the authors of this article). According to  Sex and gender: What is the difference?: “Sex” refers to the physical differences between people who are male, female, or intersex. A person typically has their sex assigned at birth based on physiological characteristics, including their genitalia and chromosome composition. This assigned sex is called a person’s “natal sex.” Gender, on the other hand, involves how a person identifies. Unlike natal sex, gender is not made up of binary forms: instead there is a broad spectrum of genders (a glossary of terms relating to gender may be found in this link).

Most orthopaedic studies comparing male and female patients, such as that presented above, are studies of the effect of sex, rather than gender.

Consider, for example, the chart below from "The “tipping point” for 931 elective shoulder arthroplasties  (see this link)." This graph shows a clear difference between the tipping point for elective arthroplasty between patients of male and female sex. Female patients coming to shoulder arthroplasty had worse preoperative self-assessed shoulder comfort and function. 

Consider also the effect of patient sex on arthritic glenohumeral anatomy as investigated in Prearthroplasty glenohumeral pathoanatomy and its relationship to patient’s sex, age, diagnosis, and self-assessed shoulder comfort and function. 

Patient sex had a strong effect on the distribution of glenoid types.

and on glenoid version

and on the degree of decentering

The chart below is from Factors Affecting Length of Stay, Readmission, and Revision after Shoulder Arthroplasty, showing the effect of patient sex on length of stay.

In, Correlates with comfort and function after total shoulder arthroplasty for degenerative joint disease, the strongest correlates with postoperative shoulder function included male sex (P<0001), and preoperative physical function (P <0001), social function (P <0001), mental health (P <0001) and shoulder function (P <0001).

Gender identification was not assessed in the studies above.

Rather than focusing on patient sex alone, medical systems are now paying deserved attention to patient gender and documenting some of the important information in the medical record.

As the importance of gender identification is being recognized and documented in medical records, future studies of patients having shoulder arthroplasty are likely to identify differences - not only between the sexes, but also among genders - in preoperative characteristics (height, weight, age, disability, expectations), tipping point for surgery, type of surgery elected, complications and outcomes.

Finally as emphasized in Equity360: Gender, Race, and Ethnicity—Title IX Turns 50:

Women Athletes Are Still Fighting Against Gender Disparities in Sports, transgender individuals may augment or suppress their sex hormone levels which, in turn, may affect bone density and periprosthetic fracture risk as well as the risk of infection after shoulder arthroplasty. See 

Association Between Serum Testosterone Levels and Cutibacterium Skin Load in Patients Undergoing Elective Shoulder Arthroplasty: A Cohort Study and Factors predictive of Cutibacterium periprosthetic shoulder infections: a retrospective study of 342 prosthetic revisions.

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How you can support research in shoulder surgery Click on this link.

Here are some videos that are of shoulder interest

Shoulder arthritis - what you need to know (see this link)

Shoulder arthritis - x-ray appearance (see this link)

The smooth and move for irreparable cuff tears (see this link)

The total shoulder arthroplasty (see this link).

The ream and run technique is shown in this link.

The cuff tear arthropathy arthroplasty (see this link).

The reverse total shoulder arthroplasty (see this link).

Sex and the shoulder

Sex-specific Analysis of Data in High-impact Orthopaedic Journals: How Are We Doing?

These authors sought to determine the degree to which sex was considered in published orthopedic research and whether the trend showed an increase in the proportion of articles with sex-specific reporting over time, however sex-specific analysis was found in less than 1/3 of the studies.

They concluded, "Where evaluating conditions that affect males and females, studies should be designed with sufficient sample size to allow for subgroup analysis by sex to be performed, and they should include sex-specific differences among the a priori research questions."

Comment: We have consistently advocated for the inclusion of patient factors, including sex, in natural history and in therapeutic outcome studies. We have pushed the need for inclusion of the 4 P's in such studies: Patient, Problem, Physician, and Procedure (see here and here, for example).

Over the years, we have pointed out that when the severity of the condition and age are matched, the self-reported shoulder status reported by women using the Simple Shoulder Test is lower than that of males of comparable age as shown again here and here. We have also shown that the sex distribution can vary widely among different practices, so that consideration of sex in the comparison of results is critical. We have pointed out that women tend to have different arthritic pathoanatomy than males. The difference in range of motion between the shoulders of men and women is well recognized. We have shown that sex is a factor predictive of outcome, as shown here. Most recently, we have shown that sex is an important factor affecting the length of stay after shoulder arthroplasty.

Thus the importance of including patient sex as a factor in natural history and outcome studies is inescapable.  Women ≠ men. As the French would say, 'vive la difference!'

However, in our enthusiasm for considering sex, we must also consider the many other important patient factors that may have comparable importance: race, age, insurance, comorbidities, smoking status, and mental health. The need to include these key variables makes large sample size critical in clinical research.

P.s. The difference between sex and gender can be confusing. According to the World Health Organization,
Sex refers to the biological and physiological characteristics that define men and women.
Gender refers to the socially constructed roles, behaviors, activities, and attributes that a given society considers appropriate for men and women.
In the current era where hormones and surgery can change the characteristics that traditionally define male and female, we will have to sort out whether we should be studying the effect of sex or gender or both.

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Consultation for those who live a distance away from Seattle.

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Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

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The effect of income, race and gender on outcome of joint arthroplasty. The 4Ps

Impact of Socioeconomic Factors on Outcome of Total Knee Arthroplasty

These authors sought evidence on the impact of socioeconomic factors on the outcome of total knee arthroplasty in patients under 60 years of age. As is the case for the post from December 20, this fits nicely with the concept that the outcome of any arthroplasty depends on the 4Ps: the problem, the patient, the procedure and the physician performing the surgery. While prior studies have focused primarily on surgical technique, implant details, and individual patient clinical factors, the focus here is on patient demographics and socioeconomic factors.

They surveyed 661 patients (average age, 54 years; range, 18–60 years; 61% female) 1 to 4 years after undergoing modern primary TKA for noninflammatory arthritis at five orthopaedic centers. Interestingly the data were collected by an independent third party with expertise in collecting healthcare data for state and federal agencies and blinded to all details regarding the patient and the care rendered. 

They found that patients reporting incomes of less than $25,000 were less likely to be satisfied with arthroplasty outcomes and more likely to have functional limitations after surgery than patients with higher incomes. Women were less likely to be satisfied and more likely to have functional limitations than men, and minority patients were more likely to have functional limitations than nonminority patients. The type of implant was not associated with outcomes after surgery. Household income was more important than minority status in predisposing to suboptimal results. After adjusting for socioeconomic factors, minority patients (Hispanic and black) reported inferior results on the functional outcome measures. 

They conclude that socioeconomic factors, in particular low income, are more strongly associated with satisfaction and functional outcomes in young patients after arthroplasty than demographic or implant factors. 

Since different clinical case series will have different mixes of diagnoses (the problem), patient factors (age, gender, overall health, socioeconomic factors, ethnicity, and insurance coverage), prostheses, and levels of physician experience, comparisons between studies will need to carefully control for these key variables.  It is also apparent that these factors may not be independent one of the others. Less healthy, less wealthy, more severely affected, patients may be more likely to receive care by less experienced surgeons, for example (N.B. this study only included high volume centers so that the effect of income, ethnicity, surgeon volume, etc may have been less than when 'all comers' are included).

The bottom line is that even though there is much marketing of the 'advantages' of one prosthesis over another, the problem, the patient and the physician are likely to be the more important of the "P"s in affecting the result of surgery.

The effect of race and income observed here has importance with respect to health care policy, access to health care, and profiling of hospitals and physicians with respect to the outcome of arthroplasty.

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Consultation for those who live a distance away from Seattle.

**Check out the new Shoulder Arthritis Book - click here.**

To see the topics covered in this Blog, click here

Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

See from which cities our patients come.

How Much Are Upper or Lower Extremity Disabilities Associated with General Health Status in the Elderly? CORR

How Much Are Upper or Lower Extremity Disabilities Associated with General Health Status in the Elderly? CORR

This paper uses a population of 272 individuals without a history of surgery for musculoskeletal disease or trauma to test the hypothesis that the DASH score (Disabilities of the Arm Shoulder and Hand - a self-reported measure of upper extremity comfort and function) is correlated with the SF 36 (a self-reported measure of overall well-being. Not surprisingly, the results of the two are correlated, the DASH is particularly associated with the physical component summary scale of the SF 36.

In that there was no documentation of the presence of upper extremity disability in these individuals, one might expect that the observed effect would have been even stronger in those with known rotator cuff tears, arthritis, carpal tunnel syndrome and the like. We have previously reported on the correlation of comorbidity with function of the shoulder and health status of patients who have glenohumeral degenerative joint disease and on the relationship of the SF 36 and shoulder function in degenerative disease and rheumatoid arthritis.

What was particularly interesting was the effect of gender and age on the DASH. Recalling that a score of 0 is no disability and 100 is total disability, males averaged a score of 15.67 ± 13.34 while women average 27.07 ± 20.00 (p<0.001). Individuals aged 65 to 75 averaged 19.60 ± 17.20 while those over 75 averaged  24.68 ± 18.80 (p<0.029).  This indicates that, in contrast to the usual practice, DASH scores need to be normalized by age and gender and that combining ages and genders in reporting results may lead to erroneous conclusions.

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Use the "Search the Blog" box to the right to find other topics of interest to you. 

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery.

See the countries from which our readers come on this post.